神经肽S镇痛活性研究，及[Tyr~6]γ2-MSH（6-12）在脊髓水平的痛觉调节作用
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摘要
第一部分：神经肽S镇痛活性研究
神经肽S(NPS)是最近发现的生物活性肽，具有调节觉醒、焦虑、运动和摄食的功能。NPS受体(NPSR)分布于下行控制系统，如中脑导水管周围灰质(periaqueductal gray，PAG)、中缝核(raphe nuclei)、侧臂旁核(lateral parabrachial nucleus，PBN)等，暗示了NPS-NPSR系统在痛觉调节中的可能作用。我们使用甩尾实验和热板实验首次评价了NPS在脊髓上水平的痛觉调节作用。在两种急性热痛觉模型中，侧脑室注射NPS(0．01-1nmol)能引起明显的镇痛效果。NPS(0．1nmol，i．c．v．)诱导的镇痛活性不被纳洛酮(i．c．v．共注射，10nmol或i．p．提前15分钟注射，10mg／kg)影响。而在相同的剂量条件下，纳洛酮能降低3nmol吗啡诱导的镇痛效果。NPSR的拮抗剂[D-Cys(tBu)~5]NPS(i．c．v．，3、10nmol)本身没有任何痛觉调节活性。但与NPS共注射后，能明显抑制NPS诱导的镇痛活性。这些结果表明，NPS的镇痛活性，是通过NPS受体而不是阿片受体发挥作用的；NPS-NPSR系统可能是新型止痛药的新靶点。
第二部分：[Tyr~6]γ2-MSH(6-12)在脊髓水平的痛觉调节作用
Mrg家族受体(mas-related gene，简称Mrg，也称为sensory neuron-specific receptor，SNSR)，特异地分布于脊髓三叉神经节和背根神经节的小直径感觉神经元中，在痛觉传导中发挥重要作用。我们的目的是研究MrgC激活后诱发原痛效果的机制，以及MrgC受体与N／OFQ-NOP系统在调节脊髓痛觉中相互作用。鞘内注射MrgC高效激动剂[Tyr~6]γ2-MSH(6-12)产生明显的热痛觉过敏效果(小鼠甩尾潜伏期的缩短，0．01-10pmol)，和诱发疼痛行为应答(后肢抓挠身体两侧，嘴咬或舔前后肢及尾巴，0．01-10nmol)。这种原痛效果能被NMDA受体拮抗剂非竞争性MK-801、竞争性D-APV和NO合酶抑制剂L-NAME抑制；但不受共注射NK_1受体拮抗剂L-703，606或NK_2受体拮抗剂MEN-10，376影响。
在其它实验中，[Tyr~6]γ2-MSH(6-12)诱发的疼痛行为被N／OFQ双向调节。高剂量N／OFQ(0．01-1nmol)抑制，低剂量N／OFQ(1fmol-3pmol)加强这种疼痛行为应答。另外，NOP受体拮抗剂[Nphe~1]N／OFQ(1-13)-NH_2加强[Tyr~6]γ2-MSH(6-12)诱发的原痛效果(包括热痛敏效果和疼痛行为应答)。
我们的结果表明，[Tyr~6]γ2-MSH(6-12)诱发的原痛效果是由NMDA-NO系统介导的。MrgC与N／OFQ-NOP系统在调节脊髓痛觉中存在相互作用。
PartⅠ: The studies on the antinociceptive effect ofneuropeptide S
Neuropeptide S (NPS), a recently identified bioactive peptide, was reported toregulate arousal, anxiety, motoring and feeding behaviors. NPS receptor (NPSR)mRNA was found in the area related to descending control system of pain, such as theperiaqueductal gray (PAG), raphe nuclei, and lateral parabrachial nucleus (PBN),suggesting the possible role of NPS-NPSR system in the regulation of paintransmission. In the present study, we evaluated the effects of NPS in pain modulationat the supraspinal level for the first time, using tail withdrawal test and hot-plate test inmice. NPS (mouse, 0.01-1 nmol) injected intracerebroventricularly (i.c.v.) caused asignificant increase of tail withdrawal latency and paw-licking/jumping latency in thetail withdrawal test and the hot-plate test, respectively. Antinociceptive effect elicitedby NPS (0.1 nmol, i.c.v.) was not affected by naloxone (i.c.v., 10 nmol co-injection ori.p., 10 mg/kg, 10 min prior to NPS) in both tail withdrawal test and hot-plate test.However, at the doses, naloxone significantly inhibited the antinociceptive effectinduced by morphine (i.c.v., 3 nmol). NPS (0.1 nmol, i.c.v.)-induced antinociceptionwas inhibited by co-injection with 10 nmol, but not 3 nmol [D-Cys(tBu)~5]NPS, apeptidergic antagonist identified more recently, while [D-Cys(tBu)~5]NPS (3 and 10nmol) alone induced neither hyperalgesia nor antinociception. These results revealedthat NPS could produce antinociception through NPS receptor, but not opioid receptor,and NPS-NPSR system could be a potential target for developing new analgesic drugs.
PartⅡ: The pain-modulating roles of [Tyr~6]γ2-MSH(6-12) at the spinal level
The mas-related genes (Mrgs, also known as sensory neuron-specific receptors,SNSRs) are specific expressed in small diameter sensory neurons in the trigeminal anddorsal root ganglia, suggesting an important role of the receptors in pain transmission.The present study aimed to investigate the underlying mechanism of the nociceptiveeffects after activation of MrgC, and the interaction between MrgC and N/OFQ-NOPreceptor system in modulation of nociception in mice. Intrathecal (i.t.) administrationof [Tyr~6]γ2-MSH(6-12), the most potent agonist for MrgC receptor, produced asignificant hyperalgesic response as assayed by tail-withdrawal test and a series ofcharacteristic nociceptive responses, including biting, licking and scratching, in adose-dependent manner (0.01-10pmol and 0.01-10nmol, respectively) in mice. These pronociceptive effects induced by [Tyr~6]γ2-MSH(6-12) were inhibiteddose-dependently by co-injection of competitive NMDA receptor antagonist D-APV,non-competitive NMDA receptor antagonist MK-801, and nitric oxide (NO)synthaseinhibitor L-NAME. However, the tachykinin NK_1 receptor antagonist L-703,606, andtachykinin NK_2 receptor antagonist MEN-10,376. had no influence on pronociceptiveeffects elicited by [Tyr~6]γ2-MSH(6-12).
In other groups, [Tyr~6]γ2-MSH(6-12)-induced nociceptive responses werebidirectionally regulated by the co-injection of N/OFQ. N/OFQ inhibited nociceptiveresponses at high doses (0.01-1 nmol), but potentiated the behaviors at low doses (1fmol-3 pmol). Furthermore, both hyperalgesia and nociceptive responses wereenhanced after the co-administration with NOP receptor antagonist[Nphe~1]N/OFQ(1-13)-NH_2.
These results suggest that intrathecal [Tyr~6]γ2-MSH(6-12)-induced pronociceptiveeffects may be mediated through NMDA receptor-NO system in the spinal cord, anddemonstrate the interaction between MrgC and N/OFQ-NOP receptor system in paintransmission.
神经肽S(NPS)是最近发现的生物活性肽，具有调节觉醒、焦虑、运动和摄食的功能。NPS受体(NPSR)分布于下行控制系统，如中脑导水管周围灰质(periaqueductal gray，PAG)、中缝核(raphe nuclei)、侧臂旁核(lateral parabrachial nucleus，PBN)等，暗示了NPS-NPSR系统在痛觉调节中的可能作用。我们使用甩尾实验和热板实验首次评价了NPS在脊髓上水平的痛觉调节作用。在两种急性热痛觉模型中，侧脑室注射NPS(0．01-1nmol)能引起明显的镇痛效果。NPS(0．1nmol，i．c．v．)诱导的镇痛活性不被纳洛酮(i．c．v．共注射，10nmol或i．p．提前15分钟注射，10mg／kg)影响。而在相同的剂量条件下，纳洛酮能降低3nmol吗啡诱导的镇痛效果。NPSR的拮抗剂[D-Cys(tBu)~5]NPS(i．c．v．，3、10nmol)本身没有任何痛觉调节活性。但与NPS共注射后，能明显抑制NPS诱导的镇痛活性。这些结果表明，NPS的镇痛活性，是通过NPS受体而不是阿片受体发挥作用的；NPS-NPSR系统可能是新型止痛药的新靶点。
第二部分：[Tyr~6]γ2-MSH(6-12)在脊髓水平的痛觉调节作用
Mrg家族受体(mas-related gene，简称Mrg，也称为sensory neuron-specific receptor，SNSR)，特异地分布于脊髓三叉神经节和背根神经节的小直径感觉神经元中，在痛觉传导中发挥重要作用。我们的目的是研究MrgC激活后诱发原痛效果的机制，以及MrgC受体与N／OFQ-NOP系统在调节脊髓痛觉中相互作用。鞘内注射MrgC高效激动剂[Tyr~6]γ2-MSH(6-12)产生明显的热痛觉过敏效果(小鼠甩尾潜伏期的缩短，0．01-10pmol)，和诱发疼痛行为应答(后肢抓挠身体两侧，嘴咬或舔前后肢及尾巴，0．01-10nmol)。这种原痛效果能被NMDA受体拮抗剂非竞争性MK-801、竞争性D-APV和NO合酶抑制剂L-NAME抑制；但不受共注射NK_1受体拮抗剂L-703，606或NK_2受体拮抗剂MEN-10，376影响。
在其它实验中，[Tyr~6]γ2-MSH(6-12)诱发的疼痛行为被N／OFQ双向调节。高剂量N／OFQ(0．01-1nmol)抑制，低剂量N／OFQ(1fmol-3pmol)加强这种疼痛行为应答。另外，NOP受体拮抗剂[Nphe~1]N／OFQ(1-13)-NH_2加强[Tyr~6]γ2-MSH(6-12)诱发的原痛效果(包括热痛敏效果和疼痛行为应答)。
我们的结果表明，[Tyr~6]γ2-MSH(6-12)诱发的原痛效果是由NMDA-NO系统介导的。MrgC与N／OFQ-NOP系统在调节脊髓痛觉中存在相互作用。
PartⅠ: The studies on the antinociceptive effect ofneuropeptide S
Neuropeptide S (NPS), a recently identified bioactive peptide, was reported toregulate arousal, anxiety, motoring and feeding behaviors. NPS receptor (NPSR)mRNA was found in the area related to descending control system of pain, such as theperiaqueductal gray (PAG), raphe nuclei, and lateral parabrachial nucleus (PBN),suggesting the possible role of NPS-NPSR system in the regulation of paintransmission. In the present study, we evaluated the effects of NPS in pain modulationat the supraspinal level for the first time, using tail withdrawal test and hot-plate test inmice. NPS (mouse, 0.01-1 nmol) injected intracerebroventricularly (i.c.v.) caused asignificant increase of tail withdrawal latency and paw-licking/jumping latency in thetail withdrawal test and the hot-plate test, respectively. Antinociceptive effect elicitedby NPS (0.1 nmol, i.c.v.) was not affected by naloxone (i.c.v., 10 nmol co-injection ori.p., 10 mg/kg, 10 min prior to NPS) in both tail withdrawal test and hot-plate test.However, at the doses, naloxone significantly inhibited the antinociceptive effectinduced by morphine (i.c.v., 3 nmol). NPS (0.1 nmol, i.c.v.)-induced antinociceptionwas inhibited by co-injection with 10 nmol, but not 3 nmol [D-Cys(tBu)~5]NPS, apeptidergic antagonist identified more recently, while [D-Cys(tBu)~5]NPS (3 and 10nmol) alone induced neither hyperalgesia nor antinociception. These results revealedthat NPS could produce antinociception through NPS receptor, but not opioid receptor,and NPS-NPSR system could be a potential target for developing new analgesic drugs.
PartⅡ: The pain-modulating roles of [Tyr~6]γ2-MSH(6-12) at the spinal level
The mas-related genes (Mrgs, also known as sensory neuron-specific receptors,SNSRs) are specific expressed in small diameter sensory neurons in the trigeminal anddorsal root ganglia, suggesting an important role of the receptors in pain transmission.The present study aimed to investigate the underlying mechanism of the nociceptiveeffects after activation of MrgC, and the interaction between MrgC and N/OFQ-NOPreceptor system in modulation of nociception in mice. Intrathecal (i.t.) administrationof [Tyr~6]γ2-MSH(6-12), the most potent agonist for MrgC receptor, produced asignificant hyperalgesic response as assayed by tail-withdrawal test and a series ofcharacteristic nociceptive responses, including biting, licking and scratching, in adose-dependent manner (0.01-10pmol and 0.01-10nmol, respectively) in mice. These pronociceptive effects induced by [Tyr~6]γ2-MSH(6-12) were inhibiteddose-dependently by co-injection of competitive NMDA receptor antagonist D-APV,non-competitive NMDA receptor antagonist MK-801, and nitric oxide (NO)synthaseinhibitor L-NAME. However, the tachykinin NK_1 receptor antagonist L-703,606, andtachykinin NK_2 receptor antagonist MEN-10,376. had no influence on pronociceptiveeffects elicited by [Tyr~6]γ2-MSH(6-12).
In other groups, [Tyr~6]γ2-MSH(6-12)-induced nociceptive responses werebidirectionally regulated by the co-injection of N/OFQ. N/OFQ inhibited nociceptiveresponses at high doses (0.01-1 nmol), but potentiated the behaviors at low doses (1fmol-3 pmol). Furthermore, both hyperalgesia and nociceptive responses wereenhanced after the co-administration with NOP receptor antagonist[Nphe~1]N/OFQ(1-13)-NH_2.
These results suggest that intrathecal [Tyr~6]γ2-MSH(6-12)-induced pronociceptiveeffects may be mediated through NMDA receptor-NO system in the spinal cord, anddemonstrate the interaction between MrgC and N/OFQ-NOP receptor system in paintransmission.
引文
[1] Laitinen T, Polvi A, Rydman P, Vendelin J, Pulkkinen V, Salmikangas P, Makela S, Rehn M, Pirskanen A, Rautanen A, Zucchelli M, Gullsten H, Leino M, Alenius H, Petays T, Haahtela T, Laitinen A, Laprise C, Hudson TJ, Laitinen LA, Kere J. Characterization of a common susceptibility locus for asthma-related traits. Science 2004;304:300-4.
[2] Sato S, Shintani Y, Miyajima N, Yoshimura K. Novel G-protein coupled receptor protein and DNA thereof.: WO Patent application, 02/31145 A1, 2002.
[3] Xu YL, Reinscheid RK, Huitron-Resendiz S, Clark SD, Wang Z, Lin SH, Brucher FA, Zeng J, Ly NK, Henriksen SJ, de LL, Civelli O. Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects. Neuron 2004;43:487-97.
[4] Koob GF, Greenwell TN. Neuropeptide S: a novel activating anxiolytic?. Neuron 2004;43:441-2.
[5] Reinscheid RK, Xu YL, Civelli O. Neuropeptide S: a new player in the modulation of arousal and anxiety. Mol Interv 2005;5:42-6.
[6] Reinscheid RK, Xu YL. Neuropeptide S as a novel arousal promoting peptide transmitter. FEBS J 2005;272:5689-93.
[7] Reinscheid RK, Xu YL. Neuropeptide S and its receptor: a newly deorphanized G protein-coupled receptor system. Neuroscientist 2005;11:532-8.
[8] Okamura N, Reinscheid RK. Neuropeptide S: a novel modulator of stress and arousal. Stress 2007;10.-221-6.
[9] Reinscheid RK. Neuropeptide S: anatomy, pharmacology, genetics and physiological functions. Results Probl Cell Differ 2008;46:145-58.
[10] Okamura N, Reinscheid RK, Civelli O, Ohgake S, Iyo M, Hashimoto K.Protective effects of neuropeptide S against MK-801-induced psychotic-like behavior and neuropathological changes. Abstracts / Frontiers in Neuroendocrinology 2006;27:137-8.
[11] Chung S, Civelli O. Orphan neuropeptides. Novel neuropeptides modulating sleep or feeding. Neuropeptides 2006;40:233-43.
[12] Reinscheid RK. Phylogenetic appearance of neuropeptide S precursor proteins in tetrapods. Peptides 2007;28:830-7.
[13] Gupte J, Cutler G, Chen JL, Tian H. Elucidation of signaling properties of vasopressin receptor-related receptor 1 by using the chimeric receptor approach. Proc Natl Acad Sci U S A 2004;101:1508-13.
[14] Reinscheid RK, Xu YL, Okamura N, Zeng J, Chung S, Pai R, Wang Z, Civelli O. Pharmacological characterization of human and murine neuropeptide s receptor variants. J Pharmacol Exp Ther 2005;315:1338-45.
[15]Gottlieb DJ, O'Connor GT, Wilk JB. Genome-wide association of sleep and circadian phenotypes. BMC Med Genet 2007;8 Suppl 1:S9.
[16]Xu YL, Gall CM, Jackson VR, Civelli 0, Reinscheid RK. Distribution of neuropeptide S receptor mRNA and neurochemical characteristics of neuropeptide S-expressing neurons in the rat brain. J Comp Neurol 2007;500:84-102.
[17]Smith KL, Patterson M, Dhillo WS, Patel SR, Semjonous NM, Gardiner JV, Ghatei MA, Bloom SR. Neuropeptide S stimulates the hypothalamo-pituitary-adrenal axis and inhibits food intake. Endocrinology 2006;147:3510-8.
[18]Rizzi A, Vergura R, Marzola G, Ruzza C, Guerrini R, Salvadori S, Regoli D, Calo G. Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice. Br J Pharmacol 2008;154:471-9.
[19]Lage R, Dieguez C, Lopez M. Caffeine treatment regulates neuropeptide S system expression in the rat brain. Neurosci Lett 2006;410:47-51.
[20]Lage R, Gonzalez CR, Dieguez C, Lopez M. Nicotine treatment regulates neuropeptide S system expression in the rat brain. Neurotoxicology 2007;28:1129-35.
[21]Sutcliffe JG, de Lecea L. The hypocretins: setting the arousal threshold. Nat Rev Neurosci 2002;3:339-49.
[22]Jones BE. Arousal systems. Front Biosci 2003;8:s438-51.
[23]Saper CB, Chou TC, Scammell TE. The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci 2001;24:726-31.
[24]Crowe RR, Goedken R, Samuelson S, Wilson R, Nelson J, Jr Noyes R. Genomewide survey of panic disorder. Am J Med Genet 2001;105:105-9.
[25]Logue MW, Vieland VJ, Goedken RJ, Crowe RR. Bayesian analysis of a previously published genome screen for panic disorder reveals new and compelling evidence for linkage to chromosome 7. Am J Med Genet B Neuropsychiatr Genet 2003;121B:95-9.
[26]Okamura N, Hashimoto K, Iyo M, Shimizu E, Dempfle A, Friedel S, Reinscheid RK. Gender-specific association of a functional coding polymorphism in the Neuropeptide S receptor gene with panic disorder but not with schizophrenia or attention-deficit/hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:1444-8.
[27]Leonard SK, Dwyer JM, Sukoff RS, Platt B, Logue SF, Neal SJ, Malberg JE, Beyer CE, Schechter LE, Rosenzweig-Lipson S, Ring RH. Pharmacology of neuropeptide S in mice: therapeutic relevance to anxiety disorders. Psychopharmacology (Berl) 2008;197:601-ll.
[28]Vitale G, Filaferro M, Ruggieri V, Pennella S, Frigeri C, Rizzi A, Guerrini R,Calo G. Anxiolytic-like effect of neuropeptide S in the rat defensive burying. Peptides2008;29:2286-91.
[29]Paneda C, Huitron-Resendiz S, Frago LM, Chowen JA, Picetti R, de Lecea L,Roberts AJ. Neuropeptide S reinstates cocaine-seeking behavior and increases locomotor activity through corticotropin-releasing factor receptor 1 in mice. J Neurosci 2009;29:4155-61.
[30]Swanson LW, Petrovich GD. What is the amygdala?. Trends Neurosci 1998;21:323-31.
[31]McGaugh JL. The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annu Rev Neurosci 2004;27:1-28.
[32]Sah P, Faber ES, de Lopez AM, Power J. The amygdaloid complex: anatomy and physiology. Physiol Rev 2003;83:803-34.
[33]Koob GF, Heinrichs SC. A role for corticotropin releasing factor and urocortin in behavioral responses to stressors. Brain Res 1999;848:141-52.
[34]Heinrichs SC, Koob GF. Corticotropin-releasing factor in brain: a role in activation, arousal, and affect regulation. J Pharmacol Exp Ther 2004;311:427-40.
[35]Millan MJ. The neurobiology and control of anxious states. Prog Neurobiol 2003 ;70:83-244.
[36]Meis S, Bergado-Acosta JR, Yanagawa Y, Obata K, Stork O, Munsch T. Identification of a neuropeptide S responsive circuitry shaping amygdala activity via the endopiriform nucleus. PLoS ONE 2008;3:e2695.
[37]Jungling K, Seidenbecher T, Sosulina L, Lesting J, Sangha S, Clark SD, Okamura N, Duangdao DM, Xu YL, Reinscheid RK, Pape HC. Neuropeptide S-mediated control of fear expression and extinction: role of intercalated GABAergic neurons in the amygdala. Neuron 2008;59:298-310.
[38]Marowsky A, Yanagawa Y, Obata K, Vogt KE. A specialized subclass of interneurons mediates dopaminergic facilitation of amygdala function. Neuron 2005;48:1025-37.
[39]Royer S, Martina M, Pare D. An inhibitory interface gates impulse traffic between the input and output stations of the amygdala. J Neurosci 1999;19:10575-83.
[40]Pare D, Quirk GJ, Ledoux JE. New vistas on amygdala networks in conditioned fear. J Neurophysiol 2004;92:l-9.
[41]Beck B, Fernette B, Stricker-Krongrad A. Peptide S is a novel potent inhibitor of voluntary and fast-induced food intake in rats. Biochem Biophys Res Commun 2005;332:859-65.
[42]Massi M, Fedeli A, Economidou D, Braconi S, Cippitelli A, Ciccocioppo R. Interactions between neuropeptide S and corticotropin releasing factor in the control of palatable food intake in rats. Appetite 2007;49:311.
[43]Niimi M. Centrally administered neuropeptide S activates orexin-containing neurons in the hypothalamus and stimulates feeding in rats. Endocrine 2006;30:75-9.
[44]Badia-Elder NE, Henderson AN, Bertholomey ML, Dodge NC, Stewart RB. The effects of neuropeptide S on ethanol drinking and other related behaviors in alcohol-preferring and -nonpreferring rats. Alcohol Clin Exp Res 2008;32:1380-7.
[45]Cline MA, Godlove DC, Nandar W, Bowden CN, Prall BC. Anorexigenic effects of central neuropeptide S involve the hypothalamus in chicks (Gallus gallus). Comp Biochem Physiol A Mol Integr Physiol 2007;148:657-63.
[46]Cline MA, Prall BC, Smith ML, Calchary WA, Siegel PB. Differential appetite-related responses to central neuropeptide S in lines of chickens divergently selected for low or high body weight. J Neuroendocrinol 2008;20:904-8.
[47]Kormann MS, Carr D, Klopp N, Illig T, Leupold W, Fritzsch C, Weiland SK, von Mutius E, Kabesch M. G-Protein-coupled receptor polymorphisms are associated with asthma in a large German population. Am J Respir Crit Care Med2005;171:1358-62.
[48]Feng Y, Hong X, Wang L, Jiang S, Chen C, Wang B, Yang J, Fang Z, Zang T, Xu X, Xu X. G protein-coupled receptor 154 gene polymorphism is associated with airway hyperresponsiveness to methacholine in a Chinese population. J Allergy Clin Immunol 2006;l 17:612-7.
[49]Vendelin J, Pulkkinen V, Rehn M, Pirskanen A, Raisanen-Sokolowski A,Laitinen A, Laitinen LA, Kere J, Laitinen T. Characterization of GPRA, a novel G protein-coupled receptor related to asthma. Am J Respir Cell Mol Biol 2005;33:262-70.
[50]Pulkkinen V, Majuri ML, Wang G, Holopainen P, Obase Y, Vendelin J, Wolff H, Rytila P, Laitinen LA, Haahtela T, Laitinen T, Alenius H, Kere J, Rehn M. Neuropeptide S and G protein-coupled receptor 154 modulate macrophage immune responses. Hum Mol Genet 2006; 15:1667-79.
[51]Vendelin J, Bruce S, Holopainen P, Pulkkinen V, Rytila P, Pirskanen A, Rehn M, Laitinen T, Laitinen LA, Haahtela T, Saarialho-Kere U, Laitinen A, Kere J. Downstream target genes of the neuropeptide S-NPSR1 pathway. Hum Mol Genet 2006;15:2923-35.
[52]Bruce S, Nyberg F, Melen E, James A, Pulkkinen V, Orsmark-Pietras C,Bergstrom A, Dahlen B, Wickman M, von Mutius E, Doekes G, Lauener R,Riedler J, Eder W, van Hage M, Pershagen G, Scheynius A, Kere J. The protective effect of farm animal exposure on childhood allergy is modified by NPSR1 polymorphisms. J Med Genet 2009;46:159-67.
[53]Orsmark-Pietras C, Melen E, Vendelin J, Bruce S, Laitinen A, Laitinen LA, Lauener R, Riedler J, von ME, Doekes G, Wickman M, van HM, Pershagen G, Scheynius A, Nyberg F, Kere J. Biological and genetic interaction between tenascin C and neuropeptide S receptor 1 in allergic diseases. Hum Mol Genet 2008;17:1673-82.
[54]Malerba G, Lindgren CM, Xumerle L, Kiviluoma P, Trabetti E, Laitinen T, Galavotti R, Pescollderungg L, Boner AL, Kere J, Pignatti PF. Chromosome 7p linkage and GPR154 gene association in Italian families with allergic asthma. Clin Exp Allergy 2007;37:83-9.
[55]Zhu HY, Wu JM, Cui TP. [Study on the association of single nucleotide polymorphisms and haplotypes of GPR154 gene with allergic asthma in Han nationality in Hubei Chinese population]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi2007;24:48-51.
[56]Melen E, Bruce S, Doekes G, Kabesch M, Laitinen T, Lauener R, Lindgren CM, Riedler J, Scheynius A, van Hage-Hamsten M, Kere J, Pershagen G, Wickman M, Nyberg F. Haplotypes of G protein-coupled receptor 154 are associated with childhood allergy and asthma. Am J Respir Crit Care Med 2005; 171:1089-95.
[57]Shin HD, Park KS, Park CS. Lack of association of GPRA (G protein-coupled receptor for asthma susceptibility) haplotypes with high serum IgE or asthma in a Korean population. J Allergy Clin Immunol 2004; 114:1226-7.
[58]Wu H, Romieu I, Sienra-Monge JJ, del RB, Burdett L, Yuenger J, Li H, Chanock SJ, London SJ. Lack of association between genetic variation in G-protein-coupled receptor for asthma susceptibility and childhood asthma and atopy. Genes Immun 2008;9:224-30.
[59]Allen IC, Pace AJ, Jania LA, Ledford JG, Latour AM, Snouwaert JN, Bernier V, Stocco R, Therien AG, Roller BH. Expression and function of NPSR1/GPRA in the lung before and after induction of asthma-like disease. Am J Physiol Lung Cell Mol Physiol 2006;291:L1005-17.
[60]D'Amato M, Bruce S, Bresso F, Zucchelli M, Ezer S, Pulkkinen V, Lindgren C, Astegiano M, Rizzetto M, Gionchetti P, Riegler G, Sostegni R, Dapemo M, D'Alfonso S, Momigliano-Richiardi P, Torkvist L, Puolakkainen P, Lappalainen M, Paavola-Sakki P, Halme L, Farkkila M, Turunen U, Kontula K, Lofberg R, Pettersson S, Kere J. Neuropeptide s receptor 1 gene polymorphism is associated with susceptibility to inflammatory bowel disease. Gastroenterology 2007;133:808-17.
[61]Satsangi J, Parkes M, Louis E, Hashimoto L, Kato N, Welsh K, Terwilliger JD,Lathrop GM, Bell JI, Jewell DP. Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12. Nat Genet 1996; 14:199-202.
[62]Ekelund E, Bradley M, Weidinger S, Jonaovic DL, Johansson C, Lindgren CM, Todorova A, Jakob T, Illig T, von Mutius E, Braun-Fahrlander C, Doekes G, Riedler J, Scheynius A, Pershagen G, Kockum I, Kere J. Lack of Association between Neuropeptide S Receptor 1 Gene (NPSR1) and Eczema in Five European Populations. Acta Derm Venereol 2009;89:l 15-21.
[63]Castro AA, Moretti M, Casagrande TS, Martinello C, Petronilho F, Steckert AV, Guerrini R, Calo' G, Dal PF, Quevedo J, Gavioli EC. Neuropeptide S produces hyperlocomotion and prevents oxidative stress damage in the mouse brain: A comparative study with amphetamine and diazepam. Pharmacol Biochem Behav 2009;91:636-42.
[64]Roth AL, Marzola E, Rizzi A, Arduin M, Trapella C, Corti C, Vergura R, Martinelli P, Salvadori S, Regoli D, Corsi M, Cavanni P, Calo G, Guerrini R. Structure-activity studies on neuropeptide S: identification of the amino acid residues crucial for receptor activation. J Biol Chem 2006;281:20809-16.
[65]Bernier V, Stocco R, Bogusky MJ, Joyce JG, Parachoniak C, Grenier K, Arget M, Mathieu MC, O'Neill GP, Slipetz D, Crackower MA, Tan CM, Therien AG. Structure-function relationships in the neuropeptide S receptor: molecular consequences of the asthma-associated mutation N107I. J Biol Chem 2006;281:24704-12.
[66]Camarda V, Trapella C, Calo G, Guerrini R, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, Salvadori S. Synthesis and biological activity of human neuropeptide S analogues modified in position 2. J Med Chem 2008;51:655-8.
[67]Camarda V, Trapella C, Calo' G, Guerrini R, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, Salvadori S. Structure-activity study at positions 3 and 4 of human neuropeptide S. Bioorg Med Chem 2008;16:8841-5.
[68]Camarda V, Rizzi A, Ruzza C, Zucchini S, Marzola G, Marzola E, Guerrini R, Salvadori S, Reinscheid RR, Regoli D, Calo' G. In vitro and in vivo pharmacological characterization of the neuropeptide S receptor antagonist [D-Cys(tBu)5]NPS. J Pharmacol Exp Ther 2009;328:549-55.
[69]Guerrini R, Camarda V, Trapella C, Calo G, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, Salvadori S. Synthesis and biological activity of human neumpeptide S analogues modified in position 5:identification of potent and pure neuropeptide S receptor antagonists. J Med Chem 2009;52:524-9.
[70] Fukatsu K, Nakayama Y, Tarui N, Mori M, Matsumoto H, Kurasawa O, Banno H. Preparation of oxazolo[3,4-a]pyrazine derivatives as TGR23 ligand antagonists. : World patent WO2005021555, 2005.
[71]Okamura N, Habay SA, Zeng J, Chamberlin AR, Reinscheid RK. Synthesis and pharmacological in vitro and in vivo profile of 3-oxo- 1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68), a selective antagonist of the neuropeptide S receptor. J Pharmacol Exp Ther 2008;325:893-901.
[72]Zhang Y, Gilmour BP, Navarro HA, Runyon SP. Identifying structural features on 1,1-diphenyl-hexahy dro-oxazolo [3,4-a]pyrazin-3-ones critical for Neuropeptide S antagonist activity. Bioorg Med Chem Lett 2008;18:4064-7.
[73]Dale Purves, Augustine GJ, Fitzpatrick D, Hall WC, Lamantia A, Mcnamara JO, Williams SM. NEUROSCIENCE, 3rd EDITION. Sunderland, Massachusetts U.S.A.: Sinauer Associates, Inc. · Publishers, 2004:209-28.
[74]Nestler EJ, Hyman SE, Malenka RC. Molecular neuropharmacology: A foundation for Clinical Neuroscience, 2nd EDITION. : McGraw-Hill Companies, 2009:269-88.
[75] Millan MJ. Descending control of pain. Prog Neurobiol 2002;66:355-474.
[76]Herz A, Millan MJ. Endogenous opioid peptides in the descending control of nociceptive responses of spinal dorsal horn neurons. Prog Brain Res 1988;77: 263-73.
[77]Pan Z, Hirakawa N, Fields HL. A cellular mechanism for the bidirectional pain-modulating actions of orphanin FQ/nociceptin. Neuron 2000;26:515-22.
[78]Chen X, Zidichouski JA, Harris KH, Jhamandas JH. Synaptic actions of neuropeptide FF in the rat parabrachial nucleus: interactions with opioid receptors. J Neurophysiol 2000;84:744-51.
[79] Ackley MA, Hurley RW, Virnich DE, Hammond DL. A cellular mechanism for the antinociceptive effect of a kappa opioid receptor agonist. Pain 2001 ;91:377-88.
[80]Li W, Gao YH, Chang M, Peng YL, Yao J, Han RW, Wang R. Neuropeptide S inhibits the acquisition and the expression of conditioned place preference to morphine in mice. Peptides 2009;30:234-40.
[81]Tzschentke TM. Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues. Prog Neurobiol 1998;56:613-72.
[82]Tzschentke TM. Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol 2007; 12:227-462.
[83]Kotlinska J, Pachuta A, Dylag T, Silberring J. Neuropeptide FF (NPFF) reduces the expression of morphine- but not of ethanol-induced conditioned place preference in rats. Peptides 2007;28:2235-42.
[84]Cunningham CL, Ferree NK, Howard MA. Apparatus bias and place conditioning with ethanol in mice. Psychopharmacology (Berl) 2003;170:409-22.
[85]Fenu S, Spina L, Rivas E, Longoni R, Di Chiara G. Morphine-conditioned single-trial place preference: role of nucleus accumbens shell dopamine receptors in acquisition, but not expression. Psychopharmacology (Berl) 2006;187:143-53.
[86]Hiroi N, White NM. The amphetamine conditioned place preference: differential involvement of dopamine receptor subtypes and two dopaminergic terminal areas. Brain Res 1991;552:141-52.
[87]Hiroi N, White NM. The lateral nucleus of the amygdala mediates expression of the amphetamine-produced conditioned place preference. J Neurosci 1991;ll:2107-16.
[88]Sellings LH, Clarke PB. Segregation of amphetamine reward and locomotor stimulation between nucleus accumbens medial shell and core. J Neurosci 2003;23:6295-303.
[89]Spanagel R, Weiss F. The dopamine hypothesis of reward: past and current status. Trends Neurosci 1999;22:521-7.
[90]Adinoff B. Neurobiologic processes in drug reward and addiction. Harv Rev Psychiatry 2004;12:305-20.
[91]Hyman SE, Malenka RC, Nestler EJ. Neural mechanisms of addiction: the role of reward-related learning and memory. Annu Rev Neurosci 2006;29:565-98.
[92]Bozarth MA. Neuroanatomical boundaries of the reward-relevant opiate-receptor field in the ventral tegmental area as mapped by the conditioned place preference method in rats. Brain Res 1987;414:77-84.
[93]Jaeger TV, van der Kooy D. Separate neural substrates mediate the motivating and discriminative properties of morphine. Behav Neurosci 1996;110:181-201.
[94]Mamoon AM, Barnes AM, Ho IK, Hoskins B. Comparative rewarding properties of morphine and butorphanol. Brain Res Bull 1995;38:507-l 1.
[95]Nader K, van der Kooy D. Deprivation state switches the neurobiological substrates mediating opiate reward in the ventral tegmental area. J Neurosci 1997;17:383-90.
[96]Olmstead MC, Franklin KB. The development of a conditioned place preference to morphine: effects of microinjections into various CNS sites. Behav Neurosci 1997;111:1324-34.
[97]Zvartau EE, Patkina NA, Morozova AS. [Reinforcing, but no analgesic, effect of opioid stimulation of the ventral tegmental area]. Biull Eksp Biol Med 1986;102:172-4.
[98]Abbott FV, Franklin KB. Morphine-6-glucuronide contributes to rewarding effects of opiates. Life Sci 1991;48:1157-63.
[99]Bals-Kubik R, Ableitner A, Herz A, Shippenberg TS. Neuroanatomical sites mediating the motivational effects of opioids as mapped by the conditioned place preference paradigm in rats. J Pharmacol Exp Ther 1993;264:489-95.
[100]Duvauchelle CL, Levitin M, MacConell LA, Lee LK, Ettenberg A. Opposite effects of prefrontal cortex and nucleus accumbens infusions of flupenthixol on stimulant-induced locomotion and brain stimulation reward. Brain Res 1992;576:104-10.
[101]White NM, McDonald RJ. Acquisition of a spatial conditioned place preference is impaired by amygdala lesions and improved by fornix lesions. Behav Brain Res 1993;55:269-81.
[102]Brown EE, Fibiger HC. Differential effects of excitotoxic lesions of the amygdala on cocaine-induced conditioned locomotion and conditioned place preference. Psychopharmacology (Berl) 1993;113:123-30.
[103]Zollner C, Stein C. Opioids. Handb Exp Pharmacol 2007:31-63.
[104]Herz A. Endogenous opioid systems and alcohol addiction. Psychopharmacology (Berl) 1997;129:99-111.
[105]Cowen MS, Lawrence AJ. The role of opioid-dopamine interactions in the induction and maintenance of ethanol consumption. Prog Neuropsychopharmacol Biol Psychiatry 1999;23:1171-212.
[106]Hall FS, Sora I, Uhl GR. Ethanol consumption and reward are decreased in mu-opiate receptor knockout mice. Psychopharmacology (Berl) 2001;154:43-9.
[107]Marchand S, Betoume A, Marty V, Daumas S, Halley H, Lassalle JM, Zajac JM, Frances B. A neuropeptide FF agonist blocks the acquisition of conditioned place preference to morphine in C57B1/6J mice. Peptides 2006;27:964-72.
[108]Koob GF, Sanna PP, Bloom FE. Neuroscience of addiction. Neuron 1998;21:467-76.
[109]Larsson A, Engel JA. Neurochemical and behavioral studies on ethanol and nicotine interactions. Neurosci Biobehav Rev 2004;27:713-20.
[110]Cannella N, Economidou D, Kallupi M, Stopponi S, Heilig M, Massi M, Ciccocioppo R. Persistent Increase of Alcohol-Seeking Evoked by Neuropeptide S: an Effect Mediated by the Hypothalamic Hypocretin System. Neuropsychopharmacol 2009.
[111]Paneda C, Huitron-Resendiz S, Frago LM, Chowen JA, Picetti R, de Lecea L, Roberts AJ. Neuropeptide S reinstates cocaine-seeking behavior and increases locomotor activity through corticotropin-releasing factor receptor 1 in mice. J Neurosci 2009;29:4155-61.
[1]Dong X, Han S, Zylka MJ, Simon MI, Anderson DJ. A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell 2001;106:619-32.
[2]Lembo PM, Grazzini E, Groblewski T, O DD, Roy MO, Zhang J, Hoffert C, Cao J, Schmidt R, Pelletier M, Labarre M, Gosselin M, Fortin Y, Banville D, Shen SH, Strom P, Payza K, Dray A, Walker P, Ahmad S. Proenkephalin A gene products activate a new family of sensory neuron-specific GPCRs. Nat Neurosci 2002;5:201-9.
[3]Zylka MJ, Dong X, Southwell AL, Anderson DJ. Atypical expansion in mice of the sensory neuron-specific Mrg G protein-coupled receptor family. Proc Natl Acad Sci U S A 2003;100:10043-8.
[4]Zhang L, Taylor N, Xie Y, Ford R, Johnson J, Paulsen JE, Bates B. Cloning and expression of MRG receptors in macaque, mouse, and human. Brain Res Mol Brain Res 2005;133:187-97.
[5]Burstein ES, Ott TR, Feddock M, Ma JN, Fuhs S, Wong S, Schiffer HH, Brann MR, Nash NR. Characterization of the Mas-related gene family: structural and functional conservation of human and rhesus MrgX receptors. Br J Pharmacol 2006;147:73-82.
[6]Wang Z, Takahashi T, Saito Y, Nagasaki H, Ly NBC, Nothacker HP, Reinscheid RK, Yang J, Chang JK, Shichiri M, Civelli 0. Salusin beta is a surrogate ligand of the mas-like G protein-coupled receptor MrgAl. Eur J Pharmacol 2006;539:145-50.
[7]Hong Y, Dai P, Jiang J, Zeng X. Dual effects of intrathecal BAM22 on nociceptive responses in acute and persistent pain-potential function of a novel receptor. Br J Pharmacol 2004;141:423-30.
[8]Bender E, Buist A, Jurzak M, Langlois X, Baggerman G, Verhasselt P, Ercken M, Guo HQ, Wintmolders C, Van WI, Van OI, Schoofs L, Luyten W. Characterization of an orphan G protein-coupled receptor localized in the dorsal root ganglia reveals adenine as a signaling molecule. Proc Natl Acad Sci U S A 2002;99:8573-8.
[9]Han SK, Dong X, Hwang JI, Zylka MJ, Anderson DJ, Simon MI. Orphan G protein-coupled receptors MrgAl and MrgCll are distinctively activated by RF-amide-related peptides through the Galpha q/11 pathway. Proc Natl Acad Sci U S A 2002;99:14740-5.
[10]Robas N, Mead E, Fidock M. MrgX2 is a high potency cortistatin receptor expressed in dorsal root ganglion. J Biol Chem 2003;278:44400-4.
[11]Kamohara M, Matsuo A, Takasaki J, Kohda M, Matsumoto M, Matsumoto S, Soga T, Hiyama H, Kobori M, Katou M. Identification of MrgX2 as a human G-protein-coupled receptor for proadrenomedullin N-terminal peptides. Biochem Biophys Res Commun 2005;330:1146-52.
[12]Nothacker HP, Wang Z, Zeng H, Mahata SK, O'Connor DT, Civelli O. Proadrenomedullin N-terminal peptide and cortistatin activation of MrgX2 receptor is based on a common structural motif. Eur J Pharmacol 2005;519:191-3.
[13]Shinohara T, Harada M, Ogi K, Maruyama M, Fujii R, Tanaka H, Fukusumi S, Komatsu H, Hosoya M, Noguchi Y, Watanabe T, Moriya T, Itoh Y, Hinuma S. Identification of a G protein-coupled receptor specifically responsive to beta-alanine. J Biol Chem 2004;279:23559-64.
[14]Zhang R, Yan PK, Zhou CH, Liao JY, Wang MW. Development of a homogeneous calcium mobilization assay for high throughput screening of mas-related gene receptor agonists. Acta Pharmacol Sin 2007;28:125-31.
[15]Gembardt F, Grajewski S, Vahl M, Schultheiss HP, Walther T. Angiotensin metabolites can stimulate receptors of the Mas-related genes family. Mol Cell Biochem 2008;319:115-23.
[16]Grazzini E, Puma C, Roy MO, Yu XH, O'Donnell D, Schmidt R, Dautrey S, Ducharme J, Perkins M, Panetta R, Laird JM, Ahmad S, Lembo PM. Sensory neuron-specific receptor activation elicits central and peripheral nociceptive effects in rats. Proc Natl Acad Sci U S A 2004;101 - 7175-80.
[17]Wroblowski B, Wigglesworth MJ, Szekeres PG, Smith GD, Rahman SS, Nicholson NH, Muir AI, Hall A, Heer JP, Garland SL, Coates WJ. The discovery of a selective, small molecule agonist for the MAS-related gene X1 receptor. J Med Chem 2009;52:818-25.
[18]Kunapuli P, Lee S, Zheng W, Alberts M, Kornienko O, Mull R, Kreamer A, Hwang JI, Simon MI, Strulovici B. Identification of small molecule antagonists of the human mas-related gene-X1 receptor. Anal Biochem 2006;351:50-61.
[19]Cox PJ, Pitcher T, Trim SA, Bell CH, Qin W, Kinloch RA. The effect of deletion of the orphan G - protein coupled receptor (GPCR) gene MrgE on pain-like behaviours in mice. Mol Pain 2008;4:2.
[20]Gustafson EL, Maguire M, Campanella M, Tarozzo G, Jia Y, Dong XW, Laverty M, Murgolo N, Priestley T, Reggiani A, Monsma F, Beltramo M. Regulation of two rat mas-related genes in a model of neuropathic pain. Brain Res Mol Brain Res 2005;142:58-64.
[21]Honan SA, McNaughton PA. Sensitisation of TRPV1 in rat sensory neurones by activation of SNSRs. Neurosci Lett 2007;422:l-6.
[22]Hager UA, Hein A, Lennerz JK, Zimmermann K, Neuhuber WL, Reeh PW. Morphological characterization of rat Mas-related G-protein-coupled receptor C and functional analysis of agonists. Neuroscience 2008; 151:242-54.
[23]Zeng X, Huang H, Hong Y. Effects of intrathecal BAM22 on noxious stimulus-evoked c-fos expression in the rat spinal dorsal horn. Brain Res 2004;1028:170-9.
[24]江剑平，洪炎国．牛肾上腺髓质22肽在吗啡耐受大鼠中对伤害性刺激引起的脊髓背角c-Fos表达的影响．中国疼痛医学杂志2007；13：166-70．
[25]Chen T, Cai Q, Hong Y. Intrathecal sensory neuron-specific receptor agonists bovine adrenal medulla 8-22 and (Tyr6)-gamma2-MSH-6-12 inhibit formalin-evoked nociception and neuronal Fos-like immunoreactivity in the spinal cord of the rat. Neuroscience 2006; 141:965-75.
[26]Cai Q, Jiang J, Chen T, Hong Y. Sensory neuron-specific receptor agonist BAM8-22 inhibits the development and expression of tolerance to morphine in rats. Behav Brain Res 2007;178:154-9.
[27]江剑平，陈雅娟，洪炎国．椎管内注射牛肾上腺髓质22肽差异性翻转吗啡耐受作用．生理学报2006；58：529-35．
[28]Chen T, Hu Z, Quirion R, Hong Y. Modulation of NMDA receptors by intrathecal administration of the sensory neuron-specific receptor agonist BAM8-22. Neuropharmacology 2008;54:796-803.
[29]Tatemoto K, Nozaki Y, Tsuda R, Konno S, Tomura K, Furuno M, Ogasawara H, Edamura K, Takagi H, Iwamura H, Noguchi M, Naito T. Immunoglobulin E-independent activation of mast cell is mediated by Mrg receptors. Biochem Biophys Res Commun 2006;349:1322-8.
[30]Lee MG, Dong X, Liu Q, Patel KN, Choi OH, Vonakis B, Undem BJ. Agonists of the MAS-related gene (Mrgs) orphan receptors as novel mediators of mast cell-sensory nerve interactions. J Immunol 2008; 180:2251-5.
[31]Uhl GR, Childers S, Pasternak G. An opiate-receptor gene family reunion. Trends Neurosci 1994;17:89-93.
[32]Mollereau C, Parmentier M, Mailleux P, Butour JL, Moisand C, Chalon P, Caput D, Vassart G, Meunier JC. ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization. Febs Lett 1994;341:33-8.
[33]Nishi M, Takeshima H, Mori M, Nakagawara K, Takeuchi T. Structure and chromosomal mapping of genes for the mouse kappa-opioid receptor and an opioid receptor homologue (MOR-C). Biochem Biophys Res Commun 1994;205:1353-7.
[34] Chen Y, Fan Y, Liu J, Mestek A, Tian M, Kozak CA, Yu L. Molecular cloning, tissue distribution and chromosomal localization of a novel member of the opioid receptor gene family. Febs Lett 1994;347:279-83.
[35]Bunzow JR, Saez C, Mortrud M, Bouvier C, Williams JT, Low M, Grandy DK. Molecular cloning and tissue distribution of a putative member of the rat opioid receptor gene family that is not a mu, delta or kappa opioid receptor type. Febs Lett 1994;347:284-8.
[36]Chen Y, Fan Y, Liu J, Mestek A, Tian M, Kozak CA, Yu L. Molecular cloning,tissue distribution and chromosomal localization of a novel member of the opioid receptor gene family. Febs Lett 1994;347:279-83.
[37]Wang JB, Johnson PS, Imai Y, Persico AM, Ozenberger BA, Eppler CM, Uhl GR. cDNA cloning of an orphan opiate receptor gene family member and its splice variant. Febs Lett 1994;348:75-9.
[38]Wick MJ, Minnerath SR, Lin X, Elde R, Law PY, Loh HH. Isolation of a novel cDNA encoding a putative membrane receptor with high homology to the cloned mu, delta, and kappa opioid receptors. Brain Res Mol Brain Res 1994;27:37-44.
[39]Lachowicz JE, Shen Y, Jr Monsma FJ, Sibley DR. Molecular cloning of a novel G protein-coupled receptor related to the opiate receptor family. J Neurochem 1995;64:34-40.
[40]Pan YX, Cheng J, Xu J, Rossi G, Jacobson E, Ryan-Moro J, Brooks AI, Dean GE, Standifer KM, Pasternak GW. Cloning and functional characterization through antisense mapping of a kappa 3-related opioid receptor. Mol Pharmacol 1995;47:1180-8.
[41]Johnson EE, McDonald J, Nicol B, Guerrini R, Lambert DG. Functional coupling of the nociceptin/orphanin FQ receptor in dog brain membranes. Brain Res 2004;1003:18-25.
[42]Meunier JC, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P, Butour JL, Guillemot JC, Ferrara P, Monsarrat B, et A. Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature 1995;377:532-5.
[43]Reinscheid RK, Nothacker HP, Bourson A, Ardati A, Henningsen RA, Bunzow JR, Grandy DK, Langen H, Jr Monsma FJ, Civelli O. Orphanin FQ: a neuropeptide that activates an opioidlike G protein-coupled receptor. Science 1995;270:792-4.
[44]Civelli O, Nothacker HP, Reinscheid R. Reverse physiology: discovery of the novel neuropeptide, orphanin FQ/nociceptin. Crit Rev Neurobiol 1998;12:163-76.
[45]Nothacker HP, Reinscheid RK, Mansour A, Henningsen RA, Ardati A, Jr Monsma FJ, Watson SJ, Civelli O. Primary structure and tissue distribution of the orphanin FQ precursor. Proc Natl Acad Sci U S A 1996;93:8677-82.
[46]Pan YX, Xu J, Pasternak GW. Cloning and expression of a cDNA encoding a mouse brain orphanin FQ/nociceptin precursor. Biochem J 1996;315 ( Pt l):11-3.
[47]Reinscheid RK, Nothacker H, Civelli O. The orphanin FQ/nociceptin gene: structure, tissue distribution of expression and functional implications obtained from knockout mice. Peptides 2000;21:901-6.
[48]Okuda-Ashitaka E, Minami T, Tachibana S, Yoshihara Y, Nishiuchi Y, Kimura T, Ito S. Nocistatin, a peptide that blocks nociceptin action in pain transmission. Nature 1998;392:286-9.
[49]Jr Neal CR, Mansour A, Reinscheid R, Nothacker HP, Civelli O, Jr Watson SJ. Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central nervous system of the rat. J Comp Neurol 1999;406:503-47.
[50]Florin S, Suaudeau C, Meunier JC, Costentin J. Orphan neuropeptide NocⅡ, a putative pronociceptin maturation product, stimulates locomotion in mice. Neuroreport 1997;8:705-7.
[51]Rossi GC, Mathis JP, Pasternak GW. Analgesic activity of orphanin FQ2, murine prepro-orphanin FQ141-157 in mice. Neuroreport 1998;9:1165-8.
[52]Calo' G, Guerrini R, Rizzi A, Salvadori S, Regoli D. Pharmacology of nociceptin and its receptor: a novel therapeutic target. Br J Pharmacol 2000;129:1261-83.
[53]Mogil JS, Pasternak GW. The molecular and behavioral pharmacology of the orphanin FQ/nociceptin peptide and receptor family. Pharmacol Rev 2001;53:381-415.
[54]Mollereau C, Mouledous L. Tissue distribution of the opioid receptor-like (ORL1) receptor. Peptides 2000;21:907-17.
[55]Mogil JS, Grisel JE, Reinscheid RK, Civelli O, Belknap JK, Grandy DK. Orphanin FQ is a functional anti-opioid peptide. Neuroscience 1996;75:333-7.
[56]Xu XJ, Hao JX, Wiesenfeld-Hallin Z. Nociceptin or antinociceptin: potent spinal antinociceptive effect of orphanin FQ/nociceptin in the rat. Neuroreport 1996;7:2092-4.
[57]Maie IA, Dickenson AH. Cholecystokinin fails to block the spinal inhibitory effects of nociceptin in sham operated and neuropathic rats. Eur J Pharmacol 2004;484:235-40.
[58]Andoh T, Itoh M, Kuraishi Y. Nociceptin gene expression in rat dorsal root ganglia induced by peripheral inflammation. Neuroreport 1997;8:2793-6.
[59]Erb K, Liebel JT, Tegeder I, Zeilhofer HU, Brune K, Geisslinger G. Spinally delivered nociceptin/orphanin FQ reduces flinching behaviour in the rat formalin test. Neuroreport 1997;8:1967-70.
[60]Sakurada C, Sakurada S, Katsuyama S, Sasaki J, Tan-No K, Sakurada T. Involvement of tachykinin NK1 receptors in nociceptin-induced hyperalgesia in mice. Brain Res 1999;841:85-92.
[61]Sakurada T, Sakurada S, Katsuyama S, Sakurada C, Tan-No K, Terenius L. Nociceptin (1-7) antagonizes nociceptin-induced hyperalgesia in mice. Br J Pharmacol 1999;128:941-4.
[62]Inoue M, Shimohira I, Yoshida A, Zimmer A, Takeshima H, Sakurada T, Ueda H. Dose-related opposite modulation by nociceptin/orphanin FQ of substance P nociception in the nociceptors and spinal cord. J Pharmacol Exp Ther 1999;291:308-13.
[63]Hao JX, Wiesenfeld-Hallin Z, Xu XJ. Lack of cross-tolerance between the antinociceptive effect of intrathecal orphanin FQ and morphine in the rat. Neurosci Lett 1997;223:49-52.
[64]Tian JH, Xu W, Zhang W, Fang Y, Grisel JE, Mogil JS, Grandy DK, Han JS. Involvement of endogenous orphanin FQ in electroacupuncture-induced analgesia. Neuroreport 1997;8:497-500.
[65]Tian JH, Xu W, Fang Y, Mogil JS, Grisel JE, Grandy DK, Han JS. Bidirectional modulatory effect of orphanin FQ on morphine-induced analgesia: antagonism in brain and potentiation in spinal cord of the rat. Br J Pharmacol 1997;120:676-80.
[66]Kamei J, Ohsawa M, Suzuki T, Saitoh A, Endoh T, Narita M, Tseng LF, Nagase H. The modulatory effect of (+)-TAN-67 on the antinociceptive effects of the nociceptin/orphanin FQ in mice. Eur J Pharmacol 1999;383:241-7.
[67]Nakano H, Minami T, Abe K, Arai T, Tokumura M, Ibii N, Okuda-Ashitaka E, Mori H, Ito S. Effect of intrathecal nocistatin on the formalin-induced pain in mice versus that of nociceptin/orphanin FQ. J Pharmacol Exp Ther 2000;292:331-6.
[68]Grisel JE, Mogil JS, Belknap JK, Grandy DK. Orphanin FQ acts as a supraspinal, but not a spinal, anti-opioid peptide. Neuroreport 1996;7:2125-9.
[69]Yamamoto T, Nozaki-Taguchi N. Effects of intrathecally administered nociceptin, an opioid receptor-like1 receptor agonist, and N-methyl-D-aspartate receptor antagonists on the thermal hyperalgesia induced by partial sciatic nerve injury in the rat. Anesthesiology 1997;87:1145-52.
[70]Vanderah TW, Raffa RB, Lashbrook J, Burritt A, Hruby V, Porreca F. Orphanin-FQ/nociceptin: lack of anti nociceptive, hyperalgesic or allodynic effects in acute thermal or mechanical tests following intracerebroventricular or intrathecal administration to mice or rats. Eur J Pain 1998;2:267-78.
[71]Jhamandas KH, Sutak M, Henderson G. Antinociceptive and morphine modulatory actions of spinal orphanin FQ. Can J Physiol Pharmacol 1998;76:314-24.
[72]Dawson-Basoa M, Gintzler AR Nociceptin (Orphanin FQ) abolishes gestational and ovarian sex steroid-induced antinociception and induces hyperalgesia. Brain Res 1997;750:48-52.
[73]Rady JJ, Campbell WB, Fujimoto JM. Antianalgesic action of nociceptin originating in the brain is mediated by spinal prostaglandin E(2) in mice. J Pharmacol Exp Ther 2001;296:7-14.
[74]Zhu CB, Zhang XL, Xu SF, Cao XD, Wu GC, Li MY, Cui DF, Qi ZW. Antagonistic effect of orphanin FQ on opioid analgesia in rat. Zhongguo Yao Li Xue Bao l998;19:10-4.
[75]Zhang XL, Zhu CB, Xu SF, Cao XD, Wu GC, Li MY, Cui DF, Chi CW. [Effect of intrathecal or intracerebroventricular administrition of OFQ on pain threshold and acpuncture analgesia in rats]. Sheng Li Xue Bao 1997;49:575-80.
[76]Yamamoto T, Sakashita Y. The role of the spinal opioid receptor like1 receptor, the NK-1 receptor, and cyclooxygenase-2 in maintaining postoperative pain in the rat. Anesth Analg 1999;89:1203-8.
[77]Hao JX, Xu IS, Wiesenfeld-Hallin Z, Xu XX Anti-hyperalgesic and anti-allodynic effects of intrathecal nociceptin/orphanin FQ in rats after spinal cord injury, peripheral nerve injury and inflammation. Pain 1998;76:385-93.
[78]King MA, Rossi GC, Chang AH, Williams L, Pasternak GW. Spinal analgesic activity of orphanin FQ/nociceptin and its fragments. Neurosci Lett 1997;223:113-6.
[79]Nazzaro C, Rizzi A, Salvadori S, Guerrini R, Regoli D, Zeilhofer HU, Calo G. UFP-101 antagonizes the spinal antinociceptive effects of nociceptin/orphanin FQ: behavioral and electrophysiological studies in mice. Peptides 2007;28:663-9.
[80]Hara N, Minami T, Okuda-Ashitaka E, Sugimoto T, Sakai M, Onaka M, Mori H, Imanishi T, Shingu K, Ito S. Characterization of nociceptin hyperalgesia and allodyniain conscious mice. Br J Pharmacol 1997;121:401-8.
[81]Sakurada T, Katsuyama S, Sakurada S, Inoue M, Tan-No K, Kisara K, Sakurada C, Ueda H, Sasaki J. Nociceptin-induced scratching, biting and licking in mice: involvement of spinal NK1 receptors. Br J Pharmacol 1999;127:1712-8.
[82]Hylden JL, Wilcox GL. Intrathecal morphine in mice: a new technique. Eur J Pharmacol 1980;67:313-6.
[83]Fairbanks CA. Spinal delivery of analgesics in experimental models of pain and analgesia. Adv Drug Deliv Rev 2003;55:1007-4l.
[84]Meller ST, Dykstra C, Gebhart GF. Acute thermal hyperalgesia in the rat is produced by activation of N-methyl-D-aspartate receptors and protein kinase C and production of nitric oxide. Neuroscience 1996;71:327-35.
[85]Aanonsen LM, Lei S, Wilcox GL. Excitatory amino acid receptors and nociceptive neurotransmission in rat spinal cord. Pain 1990;41:309-21.
[86]Coderre TJ, Katz J, Vaccarino AL, Melzack R. Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain 1993;52:259-85.
[87]Meller ST, Gebhart GF. Nitric oxide (NO) and nociceptive processing in the spinal cord. Pain 1993;52:127-36.
[88]Schaible HG, Grubb BD. Afferent and spinal mechanisms of joint pain. Pain 1993;55:5-54.
[89]Meller ST, Dykstra C, Gebhart GF. Production of endogenous nitric oxide and activation of soluble guanylate cyclase are required for N-methyl-D-aspartate-produced facilitation of the nociceptive tail-flick reflex. Eur J Pharmacol 1992;214:93-6.
[90]Kolhekar R, Meller ST, Gebhart GF. Characterization of the role of spinal N-methyl-D-aspartate receptors in thermal nociception in the rat. Neuroscience 1993;57:385-95.
[91]Raigorodsky G, Urca G. Intrathecal N-methyl-D-aspartate (NMDA) activates both nociceptive and antinociceptive systems. Brain Res 1987;422:158-62.
[92]Mjellem N, Lund A, Hole K. Reduction of NMDA-induced behaviour after acute and chronic administration of desipramine in mice. Neuropharmacology 1993;32:591-5.
[93]Sakurada T, Manome Y, Tan-No K, Sakurada S, Kisara K. The effects of substance P analogues on the scratching, biting and licking response induced by intrathecal injection of N-methyl-D-aspartate in mice. Br J Pharmacol 1990;l01:307-10.
[94]Urca G, Raigorodsky G. Behavioral classification of excitatory amino acid receptors in mouse spinal cord. Eur J Pharmacol 1988;153:211-20.
[95]Nishihara I, Minami T, Uda R, Ito S, Hyodo M, Hayaishi O. Effect of NMDA receptor antagonists on prostaglandin E2-induced hyperalgesia in conscious mice. Brain Res 1995;677:138-44.
[96]Tsuda M, Ueno S, Inoue K. In vivo pathway of thermal hyperalgesia by intrathecal administration of alpha,beta-methylene ATP in mouse spinal cord: involvement of the glutamate-NMDA receptor system. Br J Pharmacol 1999;127:449-56.
[97]Tan-No K, Taira A, Wako K, Niijima F, Nakagawasai O, Tadano T, Sakurada C, Sakurada T, Kisara K. Intrathecally administered spermine produces the scratching, biting and licking behaviour in mice. Pain 2000;86:55-61.
[98]Tan-No K, Esashi A, Nakagawasai O, Niijima F, Tadano T, Sakurada C, Sakurada T, Bakalkin G, Terenius L, Kisara K. Intrathecally administered big dynorphin, a prodynorphin-derived peptide, produces nociceptive behavior through an N-methyl-D-aspartate receptor mechanism. Brain Res 2002;952:7-14.
[99]Watanabe C, Orito T, Watanabe H, Mizoguchi H, Yonezawa A, Yanai K, Mobarakeh JI, Onodera K, Sakurada T, Sakurada S. Intrathecal high-dose histamine induces spinally-mediated nociceptive behavioral responses through a polyamine site of NMDA receptors. Eur J Pharmacol 2008;581:54-63.
[100]Sakurada S, Orito T, Sakurada C, Sato T, Hayashi T, Mobarakeh JI, Yanai K, Onodera K, Watanabe T, Sakurada T. Possible involvement of tachykinin NK(1) and NMDA receptors in histamine-induced hyperalgesia in mice. Eur J Pharmacol 2002;434:29-34.
[101]Sakurada T, Komatsu T, Sakurada S. Mechanisms of nociception evoked by intrathecal high-dose morphine. Neurotoxicology 2005;26:801-9.
[102]Sakurada T, Watanabe C, Okuda K, Sugiyama A, Moriyama T, Sakurada C, Tan-No K, Sakurada S. Intrathecal high-dose morphine induces spinally-mediated behavioral responses through NMDA receptors. Brain Res Mol Brain Res 2002;98:111-8.
[103]Tan-No K, Esashi A, Nakagawasai O, Niijima F, Sakurada C, Sakurada T, Bakalkin G, Terenius L, Tadano T. Nociceptive behavior induced by poly-L-lysine and other basic compounds involves the spinal NMDA receptors. Brain Res 2004;1008:49-53.
[104]Knowles RG, Moncada S. Nitric oxide synthases in mammals. Biochem J 1994;298 ( Pt 2):249-58.
[105]Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993;329:2002-12.
[106]Bredt DS, Hwang PM, Snyder SH. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature 1990;347:768-70.
[107]Garthwaite J. Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 1991;14:60-7.
[108]Vincent SR, Hope BT. Neurons that say NO. Trends Neurosci 1992;15:108-13.
[109]Garthwaite J, Charles SL, Chess-Williams R. Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature 1988;336:385-8.
[110]Salter M, Strijbos PJ, Neale S, Duffy C, Follenfant RL, Garthwaite J. The nitric oxide-cyclic GMP pathway is required for nociceptive signalling at specific loci within the somatosensory pathway. Neuroscience 1996;73:649-55.
[111]Malmberg AB, Yaksh TL. Spinal nitric oxide synthesis inhibition blocks NMDA-induced thermal hyperalgesia and produces antinociception in the formalin test in rats. Pain 1993;54:291-300.
[112]Meller ST, Pechman PS, Gebhart GF, Maves TJ. Nitric oxide mediates the thermal hyperalgesia produced in a model of neuropathic pain in the rat. Neuroscience 1992;50:7-10.
[113]Meller ST, Cummings CP, Traub RJ, Gebhart GF. The role of nitric oxide in the development and maintenance of the hyperalgesia produced by intraplantar injection of carrageenan in the rat. Neuroscience 1994;60:367-74.
[114]Moore PK, Oluyomi AO, Babbedge RC, Wallace P, Hart SL. L-NG-nitro arginine methyl ester exhibits antinociceptive activity in the mouse. Br J Pharmacol 1991;102:198-202.
[115]Kitto KF, Haley JE, Wilcox GL. Involvement of nitric oxide in spinally mediated hyperalgesia in the mouse. Neurosci Lett 1992;148:l-5.
[116]Komatsu T, Sakurada C, Sasaki M, Sanai K, Tsuzuki M, Bagetta G, Sakurada S, Sakurada T. Extracellular signal-regulated kinase (ERK) and nitric oxide synthase mediate intrathecal morphine-induced nociceptive behavior. Neuropharmacology 2007;52:1237-43.
[117]Sakurada T, Sugiyama A, Sakurada C, Tanno K, Sakurada S, Kisara K, Hara A, Abiko Y. Involvement of nitric oxide in spinally mediated capsaicin- and glutamate-induced behavioural responses in the mouse. Neurochem Int 1996;29:271-8.
[118]Moochhala SM, Sawynok J. Hyperalgesia produced by intrathecal substance P and related peptides: desensitization and cross desensitization. Br J Pharmacol 1984;82:381-8.
[119]Matsumura H, Sakurada T, Hara A, Sakurada S, Kisara K. Characterization of the hyperalgesic effect induced by intrathecal injection of substance P. Neuropharmacology 1985;24:421-6.
[120]Nakamura-Craig M, Gill BK. Effect of neurokinin A, substance P and calcitonin gene related peptide in peripheral hyperalgesia in the rat paw. Neurosci Lett 1991;124:49-51.
[121]Wiesenfeld-Hallin Z, Hokfelt T, Lundberg JM, Forssmann WG, Reinecke M, Tschopp FA, Fischer JA. Immunoreactive calcitonin gene-related peptide and substance P coexist in sensory neurons to the spinal cord and interact in spinal behavioral responses of the rat. Neurosci Lett 1984;52:199-204.
[122] Gamse R, Saria A. Nociceptive behavior after intrathecal injections of substance P, neurokinin A and calcitonin gene-related peptide in mice. Neurosci Lett 1986;70:143-7.
[123]Takahasi K, Sakurada T, Sakurada S, Kuwahara H, Yonezawa A, Ando R, Kisara K. Behavioural characterization of substance P-induced nociceptive response in mice. Neuropharmacology 1987;26:1289-93.
[124]Sakurada C, Sakurada S, Katsuyama S, Sasaki J, Tan-No K, Sakurada T. Involvement of tachykinin NK1 receptors in nociceptin-induced hyperalgesia in mice. Brain Res 1999;841:85-92.
[125] Sakurada T, Katsuyama S, Sakurada S, Inoue M, Tan-No K, Kisara K, Sakurada C, Ueda H, Sasaki J. Nociceptin-induced scratching, biting and licking in mice: involvement of spinal NK1 receptors. Br J Pharmacol 1999; 127:1712-8.
[126]Inoue M, Shimohira I, Yoshida A, Zimmer A, Takeshima H, Sakurada T, Ueda H. Dose-related opposite modulation by nociceptin/orphanin FQ of substance P nociception in the nociceptors and spinal cord. J Pharmacol Exp Ther 1999;291:308-13.
[127]Sakurada S, Watanabe H, Mizoguchi H, Yonezawa A, Orito T, Katsuyama S, Kuramasu A, Sakurada C, Yanai K, Sakurada T. Involvement of the histaminergic system in the nociceptin-induced pain-related behaviors in the mouse spinal cord. Pain 2004; 112:171-82.
[128]Rizzi A, Nazzaro C, Marzola GG, Zucchini S, Trapella C, Guerrini R, Zeilhofer HU, Regoli D, Calo' G. Endogenous nociceptin/orphanin FQ signalling produces opposite spinal antinociceptive and supraspinal pronociceptive effects in the mouse formalin test: pharmacological and genetic evidences. Pain 2006; 124:100-8.
[129]Yamamoto T, Nozaki-Taguchi N, Kimura S. Analgesic effect of intrathecally administered nociceptin, an opioid receptor-like1 receptor agonist, in the rat formalin test. Neuroscience 1997;81:249-54.
[130] Courteix C, Coudore-Civiale MA, Privat AM, Pelissier T, Eschalier A, Fialip J. Evidence for an exclusive antinociceptive effect of nociceptin/orphanin FQ, an endogenous ligand for the ORL1 receptor, in two animal models of neuropathic pain. Pain 2004;110:236-45.
[131]Zeilhofer HU, Calo G. Nociceptin/orphanin FQ and its receptor-potential targets for pain therapy?. J Pharmacol Exp Ther 2003;306:423-9.
[132]Inoue M, Kawashima T, Takeshima H, Calo G, Inoue A, Nakata Y, Ueda H. In vivo pain-inhibitory role of nociceptin/orphanin FQ in spinal cord. J Pharmacol Exp Ther 2003;305:495-501.
[2] Sato S, Shintani Y, Miyajima N, Yoshimura K. Novel G-protein coupled receptor protein and DNA thereof.: WO Patent application, 02/31145 A1, 2002.
[3] Xu YL, Reinscheid RK, Huitron-Resendiz S, Clark SD, Wang Z, Lin SH, Brucher FA, Zeng J, Ly NK, Henriksen SJ, de LL, Civelli O. Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects. Neuron 2004;43:487-97.
[4] Koob GF, Greenwell TN. Neuropeptide S: a novel activating anxiolytic?. Neuron 2004;43:441-2.
[5] Reinscheid RK, Xu YL, Civelli O. Neuropeptide S: a new player in the modulation of arousal and anxiety. Mol Interv 2005;5:42-6.
[6] Reinscheid RK, Xu YL. Neuropeptide S as a novel arousal promoting peptide transmitter. FEBS J 2005;272:5689-93.
[7] Reinscheid RK, Xu YL. Neuropeptide S and its receptor: a newly deorphanized G protein-coupled receptor system. Neuroscientist 2005;11:532-8.
[8] Okamura N, Reinscheid RK. Neuropeptide S: a novel modulator of stress and arousal. Stress 2007;10.-221-6.
[9] Reinscheid RK. Neuropeptide S: anatomy, pharmacology, genetics and physiological functions. Results Probl Cell Differ 2008;46:145-58.
[10] Okamura N, Reinscheid RK, Civelli O, Ohgake S, Iyo M, Hashimoto K.Protective effects of neuropeptide S against MK-801-induced psychotic-like behavior and neuropathological changes. Abstracts / Frontiers in Neuroendocrinology 2006;27:137-8.
[11] Chung S, Civelli O. Orphan neuropeptides. Novel neuropeptides modulating sleep or feeding. Neuropeptides 2006;40:233-43.
[12] Reinscheid RK. Phylogenetic appearance of neuropeptide S precursor proteins in tetrapods. Peptides 2007;28:830-7.
[13] Gupte J, Cutler G, Chen JL, Tian H. Elucidation of signaling properties of vasopressin receptor-related receptor 1 by using the chimeric receptor approach. Proc Natl Acad Sci U S A 2004;101:1508-13.
[14] Reinscheid RK, Xu YL, Okamura N, Zeng J, Chung S, Pai R, Wang Z, Civelli O. Pharmacological characterization of human and murine neuropeptide s receptor variants. J Pharmacol Exp Ther 2005;315:1338-45.
[15]Gottlieb DJ, O'Connor GT, Wilk JB. Genome-wide association of sleep and circadian phenotypes. BMC Med Genet 2007;8 Suppl 1:S9.
[16]Xu YL, Gall CM, Jackson VR, Civelli 0, Reinscheid RK. Distribution of neuropeptide S receptor mRNA and neurochemical characteristics of neuropeptide S-expressing neurons in the rat brain. J Comp Neurol 2007;500:84-102.
[17]Smith KL, Patterson M, Dhillo WS, Patel SR, Semjonous NM, Gardiner JV, Ghatei MA, Bloom SR. Neuropeptide S stimulates the hypothalamo-pituitary-adrenal axis and inhibits food intake. Endocrinology 2006;147:3510-8.
[18]Rizzi A, Vergura R, Marzola G, Ruzza C, Guerrini R, Salvadori S, Regoli D, Calo G. Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice. Br J Pharmacol 2008;154:471-9.
[19]Lage R, Dieguez C, Lopez M. Caffeine treatment regulates neuropeptide S system expression in the rat brain. Neurosci Lett 2006;410:47-51.
[20]Lage R, Gonzalez CR, Dieguez C, Lopez M. Nicotine treatment regulates neuropeptide S system expression in the rat brain. Neurotoxicology 2007;28:1129-35.
[21]Sutcliffe JG, de Lecea L. The hypocretins: setting the arousal threshold. Nat Rev Neurosci 2002;3:339-49.
[22]Jones BE. Arousal systems. Front Biosci 2003;8:s438-51.
[23]Saper CB, Chou TC, Scammell TE. The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci 2001;24:726-31.
[24]Crowe RR, Goedken R, Samuelson S, Wilson R, Nelson J, Jr Noyes R. Genomewide survey of panic disorder. Am J Med Genet 2001;105:105-9.
[25]Logue MW, Vieland VJ, Goedken RJ, Crowe RR. Bayesian analysis of a previously published genome screen for panic disorder reveals new and compelling evidence for linkage to chromosome 7. Am J Med Genet B Neuropsychiatr Genet 2003;121B:95-9.
[26]Okamura N, Hashimoto K, Iyo M, Shimizu E, Dempfle A, Friedel S, Reinscheid RK. Gender-specific association of a functional coding polymorphism in the Neuropeptide S receptor gene with panic disorder but not with schizophrenia or attention-deficit/hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:1444-8.
[27]Leonard SK, Dwyer JM, Sukoff RS, Platt B, Logue SF, Neal SJ, Malberg JE, Beyer CE, Schechter LE, Rosenzweig-Lipson S, Ring RH. Pharmacology of neuropeptide S in mice: therapeutic relevance to anxiety disorders. Psychopharmacology (Berl) 2008;197:601-ll.
[28]Vitale G, Filaferro M, Ruggieri V, Pennella S, Frigeri C, Rizzi A, Guerrini R,Calo G. Anxiolytic-like effect of neuropeptide S in the rat defensive burying. Peptides2008;29:2286-91.
[29]Paneda C, Huitron-Resendiz S, Frago LM, Chowen JA, Picetti R, de Lecea L,Roberts AJ. Neuropeptide S reinstates cocaine-seeking behavior and increases locomotor activity through corticotropin-releasing factor receptor 1 in mice. J Neurosci 2009;29:4155-61.
[30]Swanson LW, Petrovich GD. What is the amygdala?. Trends Neurosci 1998;21:323-31.
[31]McGaugh JL. The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annu Rev Neurosci 2004;27:1-28.
[32]Sah P, Faber ES, de Lopez AM, Power J. The amygdaloid complex: anatomy and physiology. Physiol Rev 2003;83:803-34.
[33]Koob GF, Heinrichs SC. A role for corticotropin releasing factor and urocortin in behavioral responses to stressors. Brain Res 1999;848:141-52.
[34]Heinrichs SC, Koob GF. Corticotropin-releasing factor in brain: a role in activation, arousal, and affect regulation. J Pharmacol Exp Ther 2004;311:427-40.
[35]Millan MJ. The neurobiology and control of anxious states. Prog Neurobiol 2003 ;70:83-244.
[36]Meis S, Bergado-Acosta JR, Yanagawa Y, Obata K, Stork O, Munsch T. Identification of a neuropeptide S responsive circuitry shaping amygdala activity via the endopiriform nucleus. PLoS ONE 2008;3:e2695.
[37]Jungling K, Seidenbecher T, Sosulina L, Lesting J, Sangha S, Clark SD, Okamura N, Duangdao DM, Xu YL, Reinscheid RK, Pape HC. Neuropeptide S-mediated control of fear expression and extinction: role of intercalated GABAergic neurons in the amygdala. Neuron 2008;59:298-310.
[38]Marowsky A, Yanagawa Y, Obata K, Vogt KE. A specialized subclass of interneurons mediates dopaminergic facilitation of amygdala function. Neuron 2005;48:1025-37.
[39]Royer S, Martina M, Pare D. An inhibitory interface gates impulse traffic between the input and output stations of the amygdala. J Neurosci 1999;19:10575-83.
[40]Pare D, Quirk GJ, Ledoux JE. New vistas on amygdala networks in conditioned fear. J Neurophysiol 2004;92:l-9.
[41]Beck B, Fernette B, Stricker-Krongrad A. Peptide S is a novel potent inhibitor of voluntary and fast-induced food intake in rats. Biochem Biophys Res Commun 2005;332:859-65.
[42]Massi M, Fedeli A, Economidou D, Braconi S, Cippitelli A, Ciccocioppo R. Interactions between neuropeptide S and corticotropin releasing factor in the control of palatable food intake in rats. Appetite 2007;49:311.
[43]Niimi M. Centrally administered neuropeptide S activates orexin-containing neurons in the hypothalamus and stimulates feeding in rats. Endocrine 2006;30:75-9.
[44]Badia-Elder NE, Henderson AN, Bertholomey ML, Dodge NC, Stewart RB. The effects of neuropeptide S on ethanol drinking and other related behaviors in alcohol-preferring and -nonpreferring rats. Alcohol Clin Exp Res 2008;32:1380-7.
[45]Cline MA, Godlove DC, Nandar W, Bowden CN, Prall BC. Anorexigenic effects of central neuropeptide S involve the hypothalamus in chicks (Gallus gallus). Comp Biochem Physiol A Mol Integr Physiol 2007;148:657-63.
[46]Cline MA, Prall BC, Smith ML, Calchary WA, Siegel PB. Differential appetite-related responses to central neuropeptide S in lines of chickens divergently selected for low or high body weight. J Neuroendocrinol 2008;20:904-8.
[47]Kormann MS, Carr D, Klopp N, Illig T, Leupold W, Fritzsch C, Weiland SK, von Mutius E, Kabesch M. G-Protein-coupled receptor polymorphisms are associated with asthma in a large German population. Am J Respir Crit Care Med2005;171:1358-62.
[48]Feng Y, Hong X, Wang L, Jiang S, Chen C, Wang B, Yang J, Fang Z, Zang T, Xu X, Xu X. G protein-coupled receptor 154 gene polymorphism is associated with airway hyperresponsiveness to methacholine in a Chinese population. J Allergy Clin Immunol 2006;l 17:612-7.
[49]Vendelin J, Pulkkinen V, Rehn M, Pirskanen A, Raisanen-Sokolowski A,Laitinen A, Laitinen LA, Kere J, Laitinen T. Characterization of GPRA, a novel G protein-coupled receptor related to asthma. Am J Respir Cell Mol Biol 2005;33:262-70.
[50]Pulkkinen V, Majuri ML, Wang G, Holopainen P, Obase Y, Vendelin J, Wolff H, Rytila P, Laitinen LA, Haahtela T, Laitinen T, Alenius H, Kere J, Rehn M. Neuropeptide S and G protein-coupled receptor 154 modulate macrophage immune responses. Hum Mol Genet 2006; 15:1667-79.
[51]Vendelin J, Bruce S, Holopainen P, Pulkkinen V, Rytila P, Pirskanen A, Rehn M, Laitinen T, Laitinen LA, Haahtela T, Saarialho-Kere U, Laitinen A, Kere J. Downstream target genes of the neuropeptide S-NPSR1 pathway. Hum Mol Genet 2006;15:2923-35.
[52]Bruce S, Nyberg F, Melen E, James A, Pulkkinen V, Orsmark-Pietras C,Bergstrom A, Dahlen B, Wickman M, von Mutius E, Doekes G, Lauener R,Riedler J, Eder W, van Hage M, Pershagen G, Scheynius A, Kere J. The protective effect of farm animal exposure on childhood allergy is modified by NPSR1 polymorphisms. J Med Genet 2009;46:159-67.
[53]Orsmark-Pietras C, Melen E, Vendelin J, Bruce S, Laitinen A, Laitinen LA, Lauener R, Riedler J, von ME, Doekes G, Wickman M, van HM, Pershagen G, Scheynius A, Nyberg F, Kere J. Biological and genetic interaction between tenascin C and neuropeptide S receptor 1 in allergic diseases. Hum Mol Genet 2008;17:1673-82.
[54]Malerba G, Lindgren CM, Xumerle L, Kiviluoma P, Trabetti E, Laitinen T, Galavotti R, Pescollderungg L, Boner AL, Kere J, Pignatti PF. Chromosome 7p linkage and GPR154 gene association in Italian families with allergic asthma. Clin Exp Allergy 2007;37:83-9.
[55]Zhu HY, Wu JM, Cui TP. [Study on the association of single nucleotide polymorphisms and haplotypes of GPR154 gene with allergic asthma in Han nationality in Hubei Chinese population]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi2007;24:48-51.
[56]Melen E, Bruce S, Doekes G, Kabesch M, Laitinen T, Lauener R, Lindgren CM, Riedler J, Scheynius A, van Hage-Hamsten M, Kere J, Pershagen G, Wickman M, Nyberg F. Haplotypes of G protein-coupled receptor 154 are associated with childhood allergy and asthma. Am J Respir Crit Care Med 2005; 171:1089-95.
[57]Shin HD, Park KS, Park CS. Lack of association of GPRA (G protein-coupled receptor for asthma susceptibility) haplotypes with high serum IgE or asthma in a Korean population. J Allergy Clin Immunol 2004; 114:1226-7.
[58]Wu H, Romieu I, Sienra-Monge JJ, del RB, Burdett L, Yuenger J, Li H, Chanock SJ, London SJ. Lack of association between genetic variation in G-protein-coupled receptor for asthma susceptibility and childhood asthma and atopy. Genes Immun 2008;9:224-30.
[59]Allen IC, Pace AJ, Jania LA, Ledford JG, Latour AM, Snouwaert JN, Bernier V, Stocco R, Therien AG, Roller BH. Expression and function of NPSR1/GPRA in the lung before and after induction of asthma-like disease. Am J Physiol Lung Cell Mol Physiol 2006;291:L1005-17.
[60]D'Amato M, Bruce S, Bresso F, Zucchelli M, Ezer S, Pulkkinen V, Lindgren C, Astegiano M, Rizzetto M, Gionchetti P, Riegler G, Sostegni R, Dapemo M, D'Alfonso S, Momigliano-Richiardi P, Torkvist L, Puolakkainen P, Lappalainen M, Paavola-Sakki P, Halme L, Farkkila M, Turunen U, Kontula K, Lofberg R, Pettersson S, Kere J. Neuropeptide s receptor 1 gene polymorphism is associated with susceptibility to inflammatory bowel disease. Gastroenterology 2007;133:808-17.
[61]Satsangi J, Parkes M, Louis E, Hashimoto L, Kato N, Welsh K, Terwilliger JD,Lathrop GM, Bell JI, Jewell DP. Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12. Nat Genet 1996; 14:199-202.
[62]Ekelund E, Bradley M, Weidinger S, Jonaovic DL, Johansson C, Lindgren CM, Todorova A, Jakob T, Illig T, von Mutius E, Braun-Fahrlander C, Doekes G, Riedler J, Scheynius A, Pershagen G, Kockum I, Kere J. Lack of Association between Neuropeptide S Receptor 1 Gene (NPSR1) and Eczema in Five European Populations. Acta Derm Venereol 2009;89:l 15-21.
[63]Castro AA, Moretti M, Casagrande TS, Martinello C, Petronilho F, Steckert AV, Guerrini R, Calo' G, Dal PF, Quevedo J, Gavioli EC. Neuropeptide S produces hyperlocomotion and prevents oxidative stress damage in the mouse brain: A comparative study with amphetamine and diazepam. Pharmacol Biochem Behav 2009;91:636-42.
[64]Roth AL, Marzola E, Rizzi A, Arduin M, Trapella C, Corti C, Vergura R, Martinelli P, Salvadori S, Regoli D, Corsi M, Cavanni P, Calo G, Guerrini R. Structure-activity studies on neuropeptide S: identification of the amino acid residues crucial for receptor activation. J Biol Chem 2006;281:20809-16.
[65]Bernier V, Stocco R, Bogusky MJ, Joyce JG, Parachoniak C, Grenier K, Arget M, Mathieu MC, O'Neill GP, Slipetz D, Crackower MA, Tan CM, Therien AG. Structure-function relationships in the neuropeptide S receptor: molecular consequences of the asthma-associated mutation N107I. J Biol Chem 2006;281:24704-12.
[66]Camarda V, Trapella C, Calo G, Guerrini R, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, Salvadori S. Synthesis and biological activity of human neuropeptide S analogues modified in position 2. J Med Chem 2008;51:655-8.
[67]Camarda V, Trapella C, Calo' G, Guerrini R, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, Salvadori S. Structure-activity study at positions 3 and 4 of human neuropeptide S. Bioorg Med Chem 2008;16:8841-5.
[68]Camarda V, Rizzi A, Ruzza C, Zucchini S, Marzola G, Marzola E, Guerrini R, Salvadori S, Reinscheid RR, Regoli D, Calo' G. In vitro and in vivo pharmacological characterization of the neuropeptide S receptor antagonist [D-Cys(tBu)5]NPS. J Pharmacol Exp Ther 2009;328:549-55.
[69]Guerrini R, Camarda V, Trapella C, Calo G, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, Salvadori S. Synthesis and biological activity of human neumpeptide S analogues modified in position 5:identification of potent and pure neuropeptide S receptor antagonists. J Med Chem 2009;52:524-9.
[70] Fukatsu K, Nakayama Y, Tarui N, Mori M, Matsumoto H, Kurasawa O, Banno H. Preparation of oxazolo[3,4-a]pyrazine derivatives as TGR23 ligand antagonists. : World patent WO2005021555, 2005.
[71]Okamura N, Habay SA, Zeng J, Chamberlin AR, Reinscheid RK. Synthesis and pharmacological in vitro and in vivo profile of 3-oxo- 1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68), a selective antagonist of the neuropeptide S receptor. J Pharmacol Exp Ther 2008;325:893-901.
[72]Zhang Y, Gilmour BP, Navarro HA, Runyon SP. Identifying structural features on 1,1-diphenyl-hexahy dro-oxazolo [3,4-a]pyrazin-3-ones critical for Neuropeptide S antagonist activity. Bioorg Med Chem Lett 2008;18:4064-7.
[73]Dale Purves, Augustine GJ, Fitzpatrick D, Hall WC, Lamantia A, Mcnamara JO, Williams SM. NEUROSCIENCE, 3rd EDITION. Sunderland, Massachusetts U.S.A.: Sinauer Associates, Inc. · Publishers, 2004:209-28.
[74]Nestler EJ, Hyman SE, Malenka RC. Molecular neuropharmacology: A foundation for Clinical Neuroscience, 2nd EDITION. : McGraw-Hill Companies, 2009:269-88.
[75] Millan MJ. Descending control of pain. Prog Neurobiol 2002;66:355-474.
[76]Herz A, Millan MJ. Endogenous opioid peptides in the descending control of nociceptive responses of spinal dorsal horn neurons. Prog Brain Res 1988;77: 263-73.
[77]Pan Z, Hirakawa N, Fields HL. A cellular mechanism for the bidirectional pain-modulating actions of orphanin FQ/nociceptin. Neuron 2000;26:515-22.
[78]Chen X, Zidichouski JA, Harris KH, Jhamandas JH. Synaptic actions of neuropeptide FF in the rat parabrachial nucleus: interactions with opioid receptors. J Neurophysiol 2000;84:744-51.
[79] Ackley MA, Hurley RW, Virnich DE, Hammond DL. A cellular mechanism for the antinociceptive effect of a kappa opioid receptor agonist. Pain 2001 ;91:377-88.
[80]Li W, Gao YH, Chang M, Peng YL, Yao J, Han RW, Wang R. Neuropeptide S inhibits the acquisition and the expression of conditioned place preference to morphine in mice. Peptides 2009;30:234-40.
[81]Tzschentke TM. Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues. Prog Neurobiol 1998;56:613-72.
[82]Tzschentke TM. Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol 2007; 12:227-462.
[83]Kotlinska J, Pachuta A, Dylag T, Silberring J. Neuropeptide FF (NPFF) reduces the expression of morphine- but not of ethanol-induced conditioned place preference in rats. Peptides 2007;28:2235-42.
[84]Cunningham CL, Ferree NK, Howard MA. Apparatus bias and place conditioning with ethanol in mice. Psychopharmacology (Berl) 2003;170:409-22.
[85]Fenu S, Spina L, Rivas E, Longoni R, Di Chiara G. Morphine-conditioned single-trial place preference: role of nucleus accumbens shell dopamine receptors in acquisition, but not expression. Psychopharmacology (Berl) 2006;187:143-53.
[86]Hiroi N, White NM. The amphetamine conditioned place preference: differential involvement of dopamine receptor subtypes and two dopaminergic terminal areas. Brain Res 1991;552:141-52.
[87]Hiroi N, White NM. The lateral nucleus of the amygdala mediates expression of the amphetamine-produced conditioned place preference. J Neurosci 1991;ll:2107-16.
[88]Sellings LH, Clarke PB. Segregation of amphetamine reward and locomotor stimulation between nucleus accumbens medial shell and core. J Neurosci 2003;23:6295-303.
[89]Spanagel R, Weiss F. The dopamine hypothesis of reward: past and current status. Trends Neurosci 1999;22:521-7.
[90]Adinoff B. Neurobiologic processes in drug reward and addiction. Harv Rev Psychiatry 2004;12:305-20.
[91]Hyman SE, Malenka RC, Nestler EJ. Neural mechanisms of addiction: the role of reward-related learning and memory. Annu Rev Neurosci 2006;29:565-98.
[92]Bozarth MA. Neuroanatomical boundaries of the reward-relevant opiate-receptor field in the ventral tegmental area as mapped by the conditioned place preference method in rats. Brain Res 1987;414:77-84.
[93]Jaeger TV, van der Kooy D. Separate neural substrates mediate the motivating and discriminative properties of morphine. Behav Neurosci 1996;110:181-201.
[94]Mamoon AM, Barnes AM, Ho IK, Hoskins B. Comparative rewarding properties of morphine and butorphanol. Brain Res Bull 1995;38:507-l 1.
[95]Nader K, van der Kooy D. Deprivation state switches the neurobiological substrates mediating opiate reward in the ventral tegmental area. J Neurosci 1997;17:383-90.
[96]Olmstead MC, Franklin KB. The development of a conditioned place preference to morphine: effects of microinjections into various CNS sites. Behav Neurosci 1997;111:1324-34.
[97]Zvartau EE, Patkina NA, Morozova AS. [Reinforcing, but no analgesic, effect of opioid stimulation of the ventral tegmental area]. Biull Eksp Biol Med 1986;102:172-4.
[98]Abbott FV, Franklin KB. Morphine-6-glucuronide contributes to rewarding effects of opiates. Life Sci 1991;48:1157-63.
[99]Bals-Kubik R, Ableitner A, Herz A, Shippenberg TS. Neuroanatomical sites mediating the motivational effects of opioids as mapped by the conditioned place preference paradigm in rats. J Pharmacol Exp Ther 1993;264:489-95.
[100]Duvauchelle CL, Levitin M, MacConell LA, Lee LK, Ettenberg A. Opposite effects of prefrontal cortex and nucleus accumbens infusions of flupenthixol on stimulant-induced locomotion and brain stimulation reward. Brain Res 1992;576:104-10.
[101]White NM, McDonald RJ. Acquisition of a spatial conditioned place preference is impaired by amygdala lesions and improved by fornix lesions. Behav Brain Res 1993;55:269-81.
[102]Brown EE, Fibiger HC. Differential effects of excitotoxic lesions of the amygdala on cocaine-induced conditioned locomotion and conditioned place preference. Psychopharmacology (Berl) 1993;113:123-30.
[103]Zollner C, Stein C. Opioids. Handb Exp Pharmacol 2007:31-63.
[104]Herz A. Endogenous opioid systems and alcohol addiction. Psychopharmacology (Berl) 1997;129:99-111.
[105]Cowen MS, Lawrence AJ. The role of opioid-dopamine interactions in the induction and maintenance of ethanol consumption. Prog Neuropsychopharmacol Biol Psychiatry 1999;23:1171-212.
[106]Hall FS, Sora I, Uhl GR. Ethanol consumption and reward are decreased in mu-opiate receptor knockout mice. Psychopharmacology (Berl) 2001;154:43-9.
[107]Marchand S, Betoume A, Marty V, Daumas S, Halley H, Lassalle JM, Zajac JM, Frances B. A neuropeptide FF agonist blocks the acquisition of conditioned place preference to morphine in C57B1/6J mice. Peptides 2006;27:964-72.
[108]Koob GF, Sanna PP, Bloom FE. Neuroscience of addiction. Neuron 1998;21:467-76.
[109]Larsson A, Engel JA. Neurochemical and behavioral studies on ethanol and nicotine interactions. Neurosci Biobehav Rev 2004;27:713-20.
[110]Cannella N, Economidou D, Kallupi M, Stopponi S, Heilig M, Massi M, Ciccocioppo R. Persistent Increase of Alcohol-Seeking Evoked by Neuropeptide S: an Effect Mediated by the Hypothalamic Hypocretin System. Neuropsychopharmacol 2009.
[111]Paneda C, Huitron-Resendiz S, Frago LM, Chowen JA, Picetti R, de Lecea L, Roberts AJ. Neuropeptide S reinstates cocaine-seeking behavior and increases locomotor activity through corticotropin-releasing factor receptor 1 in mice. J Neurosci 2009;29:4155-61.
[1]Dong X, Han S, Zylka MJ, Simon MI, Anderson DJ. A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell 2001;106:619-32.
[2]Lembo PM, Grazzini E, Groblewski T, O DD, Roy MO, Zhang J, Hoffert C, Cao J, Schmidt R, Pelletier M, Labarre M, Gosselin M, Fortin Y, Banville D, Shen SH, Strom P, Payza K, Dray A, Walker P, Ahmad S. Proenkephalin A gene products activate a new family of sensory neuron-specific GPCRs. Nat Neurosci 2002;5:201-9.
[3]Zylka MJ, Dong X, Southwell AL, Anderson DJ. Atypical expansion in mice of the sensory neuron-specific Mrg G protein-coupled receptor family. Proc Natl Acad Sci U S A 2003;100:10043-8.
[4]Zhang L, Taylor N, Xie Y, Ford R, Johnson J, Paulsen JE, Bates B. Cloning and expression of MRG receptors in macaque, mouse, and human. Brain Res Mol Brain Res 2005;133:187-97.
[5]Burstein ES, Ott TR, Feddock M, Ma JN, Fuhs S, Wong S, Schiffer HH, Brann MR, Nash NR. Characterization of the Mas-related gene family: structural and functional conservation of human and rhesus MrgX receptors. Br J Pharmacol 2006;147:73-82.
[6]Wang Z, Takahashi T, Saito Y, Nagasaki H, Ly NBC, Nothacker HP, Reinscheid RK, Yang J, Chang JK, Shichiri M, Civelli 0. Salusin beta is a surrogate ligand of the mas-like G protein-coupled receptor MrgAl. Eur J Pharmacol 2006;539:145-50.
[7]Hong Y, Dai P, Jiang J, Zeng X. Dual effects of intrathecal BAM22 on nociceptive responses in acute and persistent pain-potential function of a novel receptor. Br J Pharmacol 2004;141:423-30.
[8]Bender E, Buist A, Jurzak M, Langlois X, Baggerman G, Verhasselt P, Ercken M, Guo HQ, Wintmolders C, Van WI, Van OI, Schoofs L, Luyten W. Characterization of an orphan G protein-coupled receptor localized in the dorsal root ganglia reveals adenine as a signaling molecule. Proc Natl Acad Sci U S A 2002;99:8573-8.
[9]Han SK, Dong X, Hwang JI, Zylka MJ, Anderson DJ, Simon MI. Orphan G protein-coupled receptors MrgAl and MrgCll are distinctively activated by RF-amide-related peptides through the Galpha q/11 pathway. Proc Natl Acad Sci U S A 2002;99:14740-5.
[10]Robas N, Mead E, Fidock M. MrgX2 is a high potency cortistatin receptor expressed in dorsal root ganglion. J Biol Chem 2003;278:44400-4.
[11]Kamohara M, Matsuo A, Takasaki J, Kohda M, Matsumoto M, Matsumoto S, Soga T, Hiyama H, Kobori M, Katou M. Identification of MrgX2 as a human G-protein-coupled receptor for proadrenomedullin N-terminal peptides. Biochem Biophys Res Commun 2005;330:1146-52.
[12]Nothacker HP, Wang Z, Zeng H, Mahata SK, O'Connor DT, Civelli O. Proadrenomedullin N-terminal peptide and cortistatin activation of MrgX2 receptor is based on a common structural motif. Eur J Pharmacol 2005;519:191-3.
[13]Shinohara T, Harada M, Ogi K, Maruyama M, Fujii R, Tanaka H, Fukusumi S, Komatsu H, Hosoya M, Noguchi Y, Watanabe T, Moriya T, Itoh Y, Hinuma S. Identification of a G protein-coupled receptor specifically responsive to beta-alanine. J Biol Chem 2004;279:23559-64.
[14]Zhang R, Yan PK, Zhou CH, Liao JY, Wang MW. Development of a homogeneous calcium mobilization assay for high throughput screening of mas-related gene receptor agonists. Acta Pharmacol Sin 2007;28:125-31.
[15]Gembardt F, Grajewski S, Vahl M, Schultheiss HP, Walther T. Angiotensin metabolites can stimulate receptors of the Mas-related genes family. Mol Cell Biochem 2008;319:115-23.
[16]Grazzini E, Puma C, Roy MO, Yu XH, O'Donnell D, Schmidt R, Dautrey S, Ducharme J, Perkins M, Panetta R, Laird JM, Ahmad S, Lembo PM. Sensory neuron-specific receptor activation elicits central and peripheral nociceptive effects in rats. Proc Natl Acad Sci U S A 2004;101 - 7175-80.
[17]Wroblowski B, Wigglesworth MJ, Szekeres PG, Smith GD, Rahman SS, Nicholson NH, Muir AI, Hall A, Heer JP, Garland SL, Coates WJ. The discovery of a selective, small molecule agonist for the MAS-related gene X1 receptor. J Med Chem 2009;52:818-25.
[18]Kunapuli P, Lee S, Zheng W, Alberts M, Kornienko O, Mull R, Kreamer A, Hwang JI, Simon MI, Strulovici B. Identification of small molecule antagonists of the human mas-related gene-X1 receptor. Anal Biochem 2006;351:50-61.
[19]Cox PJ, Pitcher T, Trim SA, Bell CH, Qin W, Kinloch RA. The effect of deletion of the orphan G - protein coupled receptor (GPCR) gene MrgE on pain-like behaviours in mice. Mol Pain 2008;4:2.
[20]Gustafson EL, Maguire M, Campanella M, Tarozzo G, Jia Y, Dong XW, Laverty M, Murgolo N, Priestley T, Reggiani A, Monsma F, Beltramo M. Regulation of two rat mas-related genes in a model of neuropathic pain. Brain Res Mol Brain Res 2005;142:58-64.
[21]Honan SA, McNaughton PA. Sensitisation of TRPV1 in rat sensory neurones by activation of SNSRs. Neurosci Lett 2007;422:l-6.
[22]Hager UA, Hein A, Lennerz JK, Zimmermann K, Neuhuber WL, Reeh PW. Morphological characterization of rat Mas-related G-protein-coupled receptor C and functional analysis of agonists. Neuroscience 2008; 151:242-54.
[23]Zeng X, Huang H, Hong Y. Effects of intrathecal BAM22 on noxious stimulus-evoked c-fos expression in the rat spinal dorsal horn. Brain Res 2004;1028:170-9.
[24]江剑平，洪炎国．牛肾上腺髓质22肽在吗啡耐受大鼠中对伤害性刺激引起的脊髓背角c-Fos表达的影响．中国疼痛医学杂志2007；13：166-70．
[25]Chen T, Cai Q, Hong Y. Intrathecal sensory neuron-specific receptor agonists bovine adrenal medulla 8-22 and (Tyr6)-gamma2-MSH-6-12 inhibit formalin-evoked nociception and neuronal Fos-like immunoreactivity in the spinal cord of the rat. Neuroscience 2006; 141:965-75.
[26]Cai Q, Jiang J, Chen T, Hong Y. Sensory neuron-specific receptor agonist BAM8-22 inhibits the development and expression of tolerance to morphine in rats. Behav Brain Res 2007;178:154-9.
[27]江剑平，陈雅娟，洪炎国．椎管内注射牛肾上腺髓质22肽差异性翻转吗啡耐受作用．生理学报2006；58：529-35．
[28]Chen T, Hu Z, Quirion R, Hong Y. Modulation of NMDA receptors by intrathecal administration of the sensory neuron-specific receptor agonist BAM8-22. Neuropharmacology 2008;54:796-803.
[29]Tatemoto K, Nozaki Y, Tsuda R, Konno S, Tomura K, Furuno M, Ogasawara H, Edamura K, Takagi H, Iwamura H, Noguchi M, Naito T. Immunoglobulin E-independent activation of mast cell is mediated by Mrg receptors. Biochem Biophys Res Commun 2006;349:1322-8.
[30]Lee MG, Dong X, Liu Q, Patel KN, Choi OH, Vonakis B, Undem BJ. Agonists of the MAS-related gene (Mrgs) orphan receptors as novel mediators of mast cell-sensory nerve interactions. J Immunol 2008; 180:2251-5.
[31]Uhl GR, Childers S, Pasternak G. An opiate-receptor gene family reunion. Trends Neurosci 1994;17:89-93.
[32]Mollereau C, Parmentier M, Mailleux P, Butour JL, Moisand C, Chalon P, Caput D, Vassart G, Meunier JC. ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization. Febs Lett 1994;341:33-8.
[33]Nishi M, Takeshima H, Mori M, Nakagawara K, Takeuchi T. Structure and chromosomal mapping of genes for the mouse kappa-opioid receptor and an opioid receptor homologue (MOR-C). Biochem Biophys Res Commun 1994;205:1353-7.
[34] Chen Y, Fan Y, Liu J, Mestek A, Tian M, Kozak CA, Yu L. Molecular cloning, tissue distribution and chromosomal localization of a novel member of the opioid receptor gene family. Febs Lett 1994;347:279-83.
[35]Bunzow JR, Saez C, Mortrud M, Bouvier C, Williams JT, Low M, Grandy DK. Molecular cloning and tissue distribution of a putative member of the rat opioid receptor gene family that is not a mu, delta or kappa opioid receptor type. Febs Lett 1994;347:284-8.
[36]Chen Y, Fan Y, Liu J, Mestek A, Tian M, Kozak CA, Yu L. Molecular cloning,tissue distribution and chromosomal localization of a novel member of the opioid receptor gene family. Febs Lett 1994;347:279-83.
[37]Wang JB, Johnson PS, Imai Y, Persico AM, Ozenberger BA, Eppler CM, Uhl GR. cDNA cloning of an orphan opiate receptor gene family member and its splice variant. Febs Lett 1994;348:75-9.
[38]Wick MJ, Minnerath SR, Lin X, Elde R, Law PY, Loh HH. Isolation of a novel cDNA encoding a putative membrane receptor with high homology to the cloned mu, delta, and kappa opioid receptors. Brain Res Mol Brain Res 1994;27:37-44.
[39]Lachowicz JE, Shen Y, Jr Monsma FJ, Sibley DR. Molecular cloning of a novel G protein-coupled receptor related to the opiate receptor family. J Neurochem 1995;64:34-40.
[40]Pan YX, Cheng J, Xu J, Rossi G, Jacobson E, Ryan-Moro J, Brooks AI, Dean GE, Standifer KM, Pasternak GW. Cloning and functional characterization through antisense mapping of a kappa 3-related opioid receptor. Mol Pharmacol 1995;47:1180-8.
[41]Johnson EE, McDonald J, Nicol B, Guerrini R, Lambert DG. Functional coupling of the nociceptin/orphanin FQ receptor in dog brain membranes. Brain Res 2004;1003:18-25.
[42]Meunier JC, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P, Butour JL, Guillemot JC, Ferrara P, Monsarrat B, et A. Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature 1995;377:532-5.
[43]Reinscheid RK, Nothacker HP, Bourson A, Ardati A, Henningsen RA, Bunzow JR, Grandy DK, Langen H, Jr Monsma FJ, Civelli O. Orphanin FQ: a neuropeptide that activates an opioidlike G protein-coupled receptor. Science 1995;270:792-4.
[44]Civelli O, Nothacker HP, Reinscheid R. Reverse physiology: discovery of the novel neuropeptide, orphanin FQ/nociceptin. Crit Rev Neurobiol 1998;12:163-76.
[45]Nothacker HP, Reinscheid RK, Mansour A, Henningsen RA, Ardati A, Jr Monsma FJ, Watson SJ, Civelli O. Primary structure and tissue distribution of the orphanin FQ precursor. Proc Natl Acad Sci U S A 1996;93:8677-82.
[46]Pan YX, Xu J, Pasternak GW. Cloning and expression of a cDNA encoding a mouse brain orphanin FQ/nociceptin precursor. Biochem J 1996;315 ( Pt l):11-3.
[47]Reinscheid RK, Nothacker H, Civelli O. The orphanin FQ/nociceptin gene: structure, tissue distribution of expression and functional implications obtained from knockout mice. Peptides 2000;21:901-6.
[48]Okuda-Ashitaka E, Minami T, Tachibana S, Yoshihara Y, Nishiuchi Y, Kimura T, Ito S. Nocistatin, a peptide that blocks nociceptin action in pain transmission. Nature 1998;392:286-9.
[49]Jr Neal CR, Mansour A, Reinscheid R, Nothacker HP, Civelli O, Jr Watson SJ. Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central nervous system of the rat. J Comp Neurol 1999;406:503-47.
[50]Florin S, Suaudeau C, Meunier JC, Costentin J. Orphan neuropeptide NocⅡ, a putative pronociceptin maturation product, stimulates locomotion in mice. Neuroreport 1997;8:705-7.
[51]Rossi GC, Mathis JP, Pasternak GW. Analgesic activity of orphanin FQ2, murine prepro-orphanin FQ141-157 in mice. Neuroreport 1998;9:1165-8.
[52]Calo' G, Guerrini R, Rizzi A, Salvadori S, Regoli D. Pharmacology of nociceptin and its receptor: a novel therapeutic target. Br J Pharmacol 2000;129:1261-83.
[53]Mogil JS, Pasternak GW. The molecular and behavioral pharmacology of the orphanin FQ/nociceptin peptide and receptor family. Pharmacol Rev 2001;53:381-415.
[54]Mollereau C, Mouledous L. Tissue distribution of the opioid receptor-like (ORL1) receptor. Peptides 2000;21:907-17.
[55]Mogil JS, Grisel JE, Reinscheid RK, Civelli O, Belknap JK, Grandy DK. Orphanin FQ is a functional anti-opioid peptide. Neuroscience 1996;75:333-7.
[56]Xu XJ, Hao JX, Wiesenfeld-Hallin Z. Nociceptin or antinociceptin: potent spinal antinociceptive effect of orphanin FQ/nociceptin in the rat. Neuroreport 1996;7:2092-4.
[57]Maie IA, Dickenson AH. Cholecystokinin fails to block the spinal inhibitory effects of nociceptin in sham operated and neuropathic rats. Eur J Pharmacol 2004;484:235-40.
[58]Andoh T, Itoh M, Kuraishi Y. Nociceptin gene expression in rat dorsal root ganglia induced by peripheral inflammation. Neuroreport 1997;8:2793-6.
[59]Erb K, Liebel JT, Tegeder I, Zeilhofer HU, Brune K, Geisslinger G. Spinally delivered nociceptin/orphanin FQ reduces flinching behaviour in the rat formalin test. Neuroreport 1997;8:1967-70.
[60]Sakurada C, Sakurada S, Katsuyama S, Sasaki J, Tan-No K, Sakurada T. Involvement of tachykinin NK1 receptors in nociceptin-induced hyperalgesia in mice. Brain Res 1999;841:85-92.
[61]Sakurada T, Sakurada S, Katsuyama S, Sakurada C, Tan-No K, Terenius L. Nociceptin (1-7) antagonizes nociceptin-induced hyperalgesia in mice. Br J Pharmacol 1999;128:941-4.
[62]Inoue M, Shimohira I, Yoshida A, Zimmer A, Takeshima H, Sakurada T, Ueda H. Dose-related opposite modulation by nociceptin/orphanin FQ of substance P nociception in the nociceptors and spinal cord. J Pharmacol Exp Ther 1999;291:308-13.
[63]Hao JX, Wiesenfeld-Hallin Z, Xu XJ. Lack of cross-tolerance between the antinociceptive effect of intrathecal orphanin FQ and morphine in the rat. Neurosci Lett 1997;223:49-52.
[64]Tian JH, Xu W, Zhang W, Fang Y, Grisel JE, Mogil JS, Grandy DK, Han JS. Involvement of endogenous orphanin FQ in electroacupuncture-induced analgesia. Neuroreport 1997;8:497-500.
[65]Tian JH, Xu W, Fang Y, Mogil JS, Grisel JE, Grandy DK, Han JS. Bidirectional modulatory effect of orphanin FQ on morphine-induced analgesia: antagonism in brain and potentiation in spinal cord of the rat. Br J Pharmacol 1997;120:676-80.
[66]Kamei J, Ohsawa M, Suzuki T, Saitoh A, Endoh T, Narita M, Tseng LF, Nagase H. The modulatory effect of (+)-TAN-67 on the antinociceptive effects of the nociceptin/orphanin FQ in mice. Eur J Pharmacol 1999;383:241-7.
[67]Nakano H, Minami T, Abe K, Arai T, Tokumura M, Ibii N, Okuda-Ashitaka E, Mori H, Ito S. Effect of intrathecal nocistatin on the formalin-induced pain in mice versus that of nociceptin/orphanin FQ. J Pharmacol Exp Ther 2000;292:331-6.
[68]Grisel JE, Mogil JS, Belknap JK, Grandy DK. Orphanin FQ acts as a supraspinal, but not a spinal, anti-opioid peptide. Neuroreport 1996;7:2125-9.
[69]Yamamoto T, Nozaki-Taguchi N. Effects of intrathecally administered nociceptin, an opioid receptor-like1 receptor agonist, and N-methyl-D-aspartate receptor antagonists on the thermal hyperalgesia induced by partial sciatic nerve injury in the rat. Anesthesiology 1997;87:1145-52.
[70]Vanderah TW, Raffa RB, Lashbrook J, Burritt A, Hruby V, Porreca F. Orphanin-FQ/nociceptin: lack of anti nociceptive, hyperalgesic or allodynic effects in acute thermal or mechanical tests following intracerebroventricular or intrathecal administration to mice or rats. Eur J Pain 1998;2:267-78.
[71]Jhamandas KH, Sutak M, Henderson G. Antinociceptive and morphine modulatory actions of spinal orphanin FQ. Can J Physiol Pharmacol 1998;76:314-24.
[72]Dawson-Basoa M, Gintzler AR Nociceptin (Orphanin FQ) abolishes gestational and ovarian sex steroid-induced antinociception and induces hyperalgesia. Brain Res 1997;750:48-52.
[73]Rady JJ, Campbell WB, Fujimoto JM. Antianalgesic action of nociceptin originating in the brain is mediated by spinal prostaglandin E(2) in mice. J Pharmacol Exp Ther 2001;296:7-14.
[74]Zhu CB, Zhang XL, Xu SF, Cao XD, Wu GC, Li MY, Cui DF, Qi ZW. Antagonistic effect of orphanin FQ on opioid analgesia in rat. Zhongguo Yao Li Xue Bao l998;19:10-4.
[75]Zhang XL, Zhu CB, Xu SF, Cao XD, Wu GC, Li MY, Cui DF, Chi CW. [Effect of intrathecal or intracerebroventricular administrition of OFQ on pain threshold and acpuncture analgesia in rats]. Sheng Li Xue Bao 1997;49:575-80.
[76]Yamamoto T, Sakashita Y. The role of the spinal opioid receptor like1 receptor, the NK-1 receptor, and cyclooxygenase-2 in maintaining postoperative pain in the rat. Anesth Analg 1999;89:1203-8.
[77]Hao JX, Xu IS, Wiesenfeld-Hallin Z, Xu XX Anti-hyperalgesic and anti-allodynic effects of intrathecal nociceptin/orphanin FQ in rats after spinal cord injury, peripheral nerve injury and inflammation. Pain 1998;76:385-93.
[78]King MA, Rossi GC, Chang AH, Williams L, Pasternak GW. Spinal analgesic activity of orphanin FQ/nociceptin and its fragments. Neurosci Lett 1997;223:113-6.
[79]Nazzaro C, Rizzi A, Salvadori S, Guerrini R, Regoli D, Zeilhofer HU, Calo G. UFP-101 antagonizes the spinal antinociceptive effects of nociceptin/orphanin FQ: behavioral and electrophysiological studies in mice. Peptides 2007;28:663-9.
[80]Hara N, Minami T, Okuda-Ashitaka E, Sugimoto T, Sakai M, Onaka M, Mori H, Imanishi T, Shingu K, Ito S. Characterization of nociceptin hyperalgesia and allodyniain conscious mice. Br J Pharmacol 1997;121:401-8.
[81]Sakurada T, Katsuyama S, Sakurada S, Inoue M, Tan-No K, Kisara K, Sakurada C, Ueda H, Sasaki J. Nociceptin-induced scratching, biting and licking in mice: involvement of spinal NK1 receptors. Br J Pharmacol 1999;127:1712-8.
[82]Hylden JL, Wilcox GL. Intrathecal morphine in mice: a new technique. Eur J Pharmacol 1980;67:313-6.
[83]Fairbanks CA. Spinal delivery of analgesics in experimental models of pain and analgesia. Adv Drug Deliv Rev 2003;55:1007-4l.
[84]Meller ST, Dykstra C, Gebhart GF. Acute thermal hyperalgesia in the rat is produced by activation of N-methyl-D-aspartate receptors and protein kinase C and production of nitric oxide. Neuroscience 1996;71:327-35.
[85]Aanonsen LM, Lei S, Wilcox GL. Excitatory amino acid receptors and nociceptive neurotransmission in rat spinal cord. Pain 1990;41:309-21.
[86]Coderre TJ, Katz J, Vaccarino AL, Melzack R. Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain 1993;52:259-85.
[87]Meller ST, Gebhart GF. Nitric oxide (NO) and nociceptive processing in the spinal cord. Pain 1993;52:127-36.
[88]Schaible HG, Grubb BD. Afferent and spinal mechanisms of joint pain. Pain 1993;55:5-54.
[89]Meller ST, Dykstra C, Gebhart GF. Production of endogenous nitric oxide and activation of soluble guanylate cyclase are required for N-methyl-D-aspartate-produced facilitation of the nociceptive tail-flick reflex. Eur J Pharmacol 1992;214:93-6.
[90]Kolhekar R, Meller ST, Gebhart GF. Characterization of the role of spinal N-methyl-D-aspartate receptors in thermal nociception in the rat. Neuroscience 1993;57:385-95.
[91]Raigorodsky G, Urca G. Intrathecal N-methyl-D-aspartate (NMDA) activates both nociceptive and antinociceptive systems. Brain Res 1987;422:158-62.
[92]Mjellem N, Lund A, Hole K. Reduction of NMDA-induced behaviour after acute and chronic administration of desipramine in mice. Neuropharmacology 1993;32:591-5.
[93]Sakurada T, Manome Y, Tan-No K, Sakurada S, Kisara K. The effects of substance P analogues on the scratching, biting and licking response induced by intrathecal injection of N-methyl-D-aspartate in mice. Br J Pharmacol 1990;l01:307-10.
[94]Urca G, Raigorodsky G. Behavioral classification of excitatory amino acid receptors in mouse spinal cord. Eur J Pharmacol 1988;153:211-20.
[95]Nishihara I, Minami T, Uda R, Ito S, Hyodo M, Hayaishi O. Effect of NMDA receptor antagonists on prostaglandin E2-induced hyperalgesia in conscious mice. Brain Res 1995;677:138-44.
[96]Tsuda M, Ueno S, Inoue K. In vivo pathway of thermal hyperalgesia by intrathecal administration of alpha,beta-methylene ATP in mouse spinal cord: involvement of the glutamate-NMDA receptor system. Br J Pharmacol 1999;127:449-56.
[97]Tan-No K, Taira A, Wako K, Niijima F, Nakagawasai O, Tadano T, Sakurada C, Sakurada T, Kisara K. Intrathecally administered spermine produces the scratching, biting and licking behaviour in mice. Pain 2000;86:55-61.
[98]Tan-No K, Esashi A, Nakagawasai O, Niijima F, Tadano T, Sakurada C, Sakurada T, Bakalkin G, Terenius L, Kisara K. Intrathecally administered big dynorphin, a prodynorphin-derived peptide, produces nociceptive behavior through an N-methyl-D-aspartate receptor mechanism. Brain Res 2002;952:7-14.
[99]Watanabe C, Orito T, Watanabe H, Mizoguchi H, Yonezawa A, Yanai K, Mobarakeh JI, Onodera K, Sakurada T, Sakurada S. Intrathecal high-dose histamine induces spinally-mediated nociceptive behavioral responses through a polyamine site of NMDA receptors. Eur J Pharmacol 2008;581:54-63.
[100]Sakurada S, Orito T, Sakurada C, Sato T, Hayashi T, Mobarakeh JI, Yanai K, Onodera K, Watanabe T, Sakurada T. Possible involvement of tachykinin NK(1) and NMDA receptors in histamine-induced hyperalgesia in mice. Eur J Pharmacol 2002;434:29-34.
[101]Sakurada T, Komatsu T, Sakurada S. Mechanisms of nociception evoked by intrathecal high-dose morphine. Neurotoxicology 2005;26:801-9.
[102]Sakurada T, Watanabe C, Okuda K, Sugiyama A, Moriyama T, Sakurada C, Tan-No K, Sakurada S. Intrathecal high-dose morphine induces spinally-mediated behavioral responses through NMDA receptors. Brain Res Mol Brain Res 2002;98:111-8.
[103]Tan-No K, Esashi A, Nakagawasai O, Niijima F, Sakurada C, Sakurada T, Bakalkin G, Terenius L, Tadano T. Nociceptive behavior induced by poly-L-lysine and other basic compounds involves the spinal NMDA receptors. Brain Res 2004;1008:49-53.
[104]Knowles RG, Moncada S. Nitric oxide synthases in mammals. Biochem J 1994;298 ( Pt 2):249-58.
[105]Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993;329:2002-12.
[106]Bredt DS, Hwang PM, Snyder SH. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature 1990;347:768-70.
[107]Garthwaite J. Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 1991;14:60-7.
[108]Vincent SR, Hope BT. Neurons that say NO. Trends Neurosci 1992;15:108-13.
[109]Garthwaite J, Charles SL, Chess-Williams R. Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature 1988;336:385-8.
[110]Salter M, Strijbos PJ, Neale S, Duffy C, Follenfant RL, Garthwaite J. The nitric oxide-cyclic GMP pathway is required for nociceptive signalling at specific loci within the somatosensory pathway. Neuroscience 1996;73:649-55.
[111]Malmberg AB, Yaksh TL. Spinal nitric oxide synthesis inhibition blocks NMDA-induced thermal hyperalgesia and produces antinociception in the formalin test in rats. Pain 1993;54:291-300.
[112]Meller ST, Pechman PS, Gebhart GF, Maves TJ. Nitric oxide mediates the thermal hyperalgesia produced in a model of neuropathic pain in the rat. Neuroscience 1992;50:7-10.
[113]Meller ST, Cummings CP, Traub RJ, Gebhart GF. The role of nitric oxide in the development and maintenance of the hyperalgesia produced by intraplantar injection of carrageenan in the rat. Neuroscience 1994;60:367-74.
[114]Moore PK, Oluyomi AO, Babbedge RC, Wallace P, Hart SL. L-NG-nitro arginine methyl ester exhibits antinociceptive activity in the mouse. Br J Pharmacol 1991;102:198-202.
[115]Kitto KF, Haley JE, Wilcox GL. Involvement of nitric oxide in spinally mediated hyperalgesia in the mouse. Neurosci Lett 1992;148:l-5.
[116]Komatsu T, Sakurada C, Sasaki M, Sanai K, Tsuzuki M, Bagetta G, Sakurada S, Sakurada T. Extracellular signal-regulated kinase (ERK) and nitric oxide synthase mediate intrathecal morphine-induced nociceptive behavior. Neuropharmacology 2007;52:1237-43.
[117]Sakurada T, Sugiyama A, Sakurada C, Tanno K, Sakurada S, Kisara K, Hara A, Abiko Y. Involvement of nitric oxide in spinally mediated capsaicin- and glutamate-induced behavioural responses in the mouse. Neurochem Int 1996;29:271-8.
[118]Moochhala SM, Sawynok J. Hyperalgesia produced by intrathecal substance P and related peptides: desensitization and cross desensitization. Br J Pharmacol 1984;82:381-8.
[119]Matsumura H, Sakurada T, Hara A, Sakurada S, Kisara K. Characterization of the hyperalgesic effect induced by intrathecal injection of substance P. Neuropharmacology 1985;24:421-6.
[120]Nakamura-Craig M, Gill BK. Effect of neurokinin A, substance P and calcitonin gene related peptide in peripheral hyperalgesia in the rat paw. Neurosci Lett 1991;124:49-51.
[121]Wiesenfeld-Hallin Z, Hokfelt T, Lundberg JM, Forssmann WG, Reinecke M, Tschopp FA, Fischer JA. Immunoreactive calcitonin gene-related peptide and substance P coexist in sensory neurons to the spinal cord and interact in spinal behavioral responses of the rat. Neurosci Lett 1984;52:199-204.
[122] Gamse R, Saria A. Nociceptive behavior after intrathecal injections of substance P, neurokinin A and calcitonin gene-related peptide in mice. Neurosci Lett 1986;70:143-7.
[123]Takahasi K, Sakurada T, Sakurada S, Kuwahara H, Yonezawa A, Ando R, Kisara K. Behavioural characterization of substance P-induced nociceptive response in mice. Neuropharmacology 1987;26:1289-93.
[124]Sakurada C, Sakurada S, Katsuyama S, Sasaki J, Tan-No K, Sakurada T. Involvement of tachykinin NK1 receptors in nociceptin-induced hyperalgesia in mice. Brain Res 1999;841:85-92.
[125] Sakurada T, Katsuyama S, Sakurada S, Inoue M, Tan-No K, Kisara K, Sakurada C, Ueda H, Sasaki J. Nociceptin-induced scratching, biting and licking in mice: involvement of spinal NK1 receptors. Br J Pharmacol 1999; 127:1712-8.
[126]Inoue M, Shimohira I, Yoshida A, Zimmer A, Takeshima H, Sakurada T, Ueda H. Dose-related opposite modulation by nociceptin/orphanin FQ of substance P nociception in the nociceptors and spinal cord. J Pharmacol Exp Ther 1999;291:308-13.
[127]Sakurada S, Watanabe H, Mizoguchi H, Yonezawa A, Orito T, Katsuyama S, Kuramasu A, Sakurada C, Yanai K, Sakurada T. Involvement of the histaminergic system in the nociceptin-induced pain-related behaviors in the mouse spinal cord. Pain 2004; 112:171-82.
[128]Rizzi A, Nazzaro C, Marzola GG, Zucchini S, Trapella C, Guerrini R, Zeilhofer HU, Regoli D, Calo' G. Endogenous nociceptin/orphanin FQ signalling produces opposite spinal antinociceptive and supraspinal pronociceptive effects in the mouse formalin test: pharmacological and genetic evidences. Pain 2006; 124:100-8.
[129]Yamamoto T, Nozaki-Taguchi N, Kimura S. Analgesic effect of intrathecally administered nociceptin, an opioid receptor-like1 receptor agonist, in the rat formalin test. Neuroscience 1997;81:249-54.
[130] Courteix C, Coudore-Civiale MA, Privat AM, Pelissier T, Eschalier A, Fialip J. Evidence for an exclusive antinociceptive effect of nociceptin/orphanin FQ, an endogenous ligand for the ORL1 receptor, in two animal models of neuropathic pain. Pain 2004;110:236-45.
[131]Zeilhofer HU, Calo G. Nociceptin/orphanin FQ and its receptor-potential targets for pain therapy?. J Pharmacol Exp Ther 2003;306:423-9.
[132]Inoue M, Kawashima T, Takeshima H, Calo G, Inoue A, Nakata Y, Ueda H. In vivo pain-inhibitory role of nociceptin/orphanin FQ in spinal cord. J Pharmacol Exp Ther 2003;305:495-501.
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