神经病理性疼痛大鼠中脑导水管周围灰质腹外侧区GABAA_(α3)表达的性别差异
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摘要
目的探讨不同性别神经病理性疼痛大鼠中脑导水管周围灰质腹外侧区(vLPAG)γ-氨基丁酸A型α3亚基(GABAA_(α3))受体表达的差异。方法大鼠24只,雌(F组)雄(M组)各12只;坐骨神经分支选择性损伤(SNI)复制大鼠神经病理性疼痛模型;记录大鼠在各时间点(术前1 d及术后1、3、7和14 d)的机械痛阈和冷痛阈。Western blot检测vLPAG处GABAA_(α3)受体的蛋白表达。结果与术前相比,F组与M组大鼠均出现明显的机械痛敏和冷痛敏反应,F组较M组机械痛阈更低(P<0.05),F组冷缩足次数多于M组(P<0.05);术后14 d vLPAG处GABAA_(α3)受体蛋白表达增加,F组明显高于M组(P<0.05)。结论神经病理性疼痛雌性大鼠较雄性大鼠更敏感,vLPAG处GABAA_(α3)受体表达的上调可能与大鼠痛阈降低有关。
Objective To investigate the gender difference of GABAA_(α3) receptor expression in the ventrolateral periaqueductal gray(vLPAG) of rats with neuropathic pain. Methods Twenty-four SD rats were divided into 2 groups: 12 females in group F and 12 males in group M. Neuropathic pain model was established by spared nerve injury(SNI) of sciatic nerve branches. The mechanical pain threshold and cold pain threshold were recorded at each time point(1 day before operation and 1, 3, 7, 14 days after operation). Western blotting was used to detect the expression level of GABAA_(α3) receptor at vLPAG. Results The mechanical and cold allodynia were significantly higher in both group F and group M after operation. The mechanical pain threshold of group F was lower than that of group M(P<0.05), and the frequency of cold foot contraction in group F was higher than that in group M(P<0.05). 14 days after the model establishment, the expression level of GABAA_(α3) receptor protein increased significantly at vLPAG, and it was higher in group F than that in group M(P<0.05). Conclusions Female rats are more sensitive to neuropathic pain than male rats and the up-regulation of GABAA_(α3) receptor expression at vLPAG is related to the decrease of pain threshold in rats.
Objective To investigate the gender difference of GABAA_(α3) receptor expression in the ventrolateral periaqueductal gray(vLPAG) of rats with neuropathic pain. Methods Twenty-four SD rats were divided into 2 groups: 12 females in group F and 12 males in group M. Neuropathic pain model was established by spared nerve injury(SNI) of sciatic nerve branches. The mechanical pain threshold and cold pain threshold were recorded at each time point(1 day before operation and 1, 3, 7, 14 days after operation). Western blotting was used to detect the expression level of GABAA_(α3) receptor at vLPAG. Results The mechanical and cold allodynia were significantly higher in both group F and group M after operation. The mechanical pain threshold of group F was lower than that of group M(P<0.05), and the frequency of cold foot contraction in group F was higher than that in group M(P<0.05). 14 days after the model establishment, the expression level of GABAA_(α3) receptor protein increased significantly at vLPAG, and it was higher in group F than that in group M(P<0.05). Conclusions Female rats are more sensitive to neuropathic pain than male rats and the up-regulation of GABAA_(α3) receptor expression at vLPAG is related to the decrease of pain threshold in rats.
引文
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[12] Paller CJ,Campbell CM,Edwards RR,et al.Sex-based differences in pain perception and treatment [J].Pain Med,2009,10:289-299.
[13] Tonsfeldt KJ,Suchland KL,Beeson KA,et al.Sex differences in GABAA signaling in the periaqueductal gray induced by persistent inflammation [J].J Neurosci,2016,36:1669-1681.
[2] Averitt DL,Eidson LN,Doyle HH,et al.Neuronal and glial factors contributing to sex differences in opioid modulation of pain [J].Neuropsychopharmacology,2019,44:155-165.
[3] Helfert SM,Reimer M,H?per J,et al.Individualized pharmacological treatment of neuropathic pain [J].Clin Pharmacol Ther,2015,97:135-142.
[4] Taati M,Tamaddonfard E.Ventrolateral orbital cortex oxytocin attenuates neuropathic pain through periaqueductal gray opioid receptor [J].Pharmacol Rep,2018,70:577-583.
[5] Ho YC,Cheng JK,Chiou LC.Hypofunction of glutamatergic neurotransmission in the periaqueductal gray contributes to nerve-injury-induced neuropathic pain [J].J Neurosci,2013,33:7825-7836.
[6] 金小高,罗爱林,张广雄.三种大鼠神经病理性疼痛模型的制备和效果比较[J].临床麻醉学杂志,2005,21:338-340.
[7] 申乐,李旭,王海棠,等.神经病理性疼痛相关蛋白质在双侧慢性缩窄性损伤大鼠脊髓后角的表达[J].中国医学科学院学报,2013,35:628-633.
[8] Afrazi S,Esmaeili-Mahani S.Allopregnanolone suppre-sses diabetes-induced neuropathic pain and motor deficit through inhibition of GABAA receptor down-regulation in the spinal cord of diabetic rats [J].Iran J Basic Med Sci,2014,17:312-317.
[9] Du L,Wang SJ,Cui J,et al.The role of HCN channels within the periaqueductal gray in neuropathic pain [J].Brain Res,2013,1500:36-44.
[10] 孙万秋,王桂芝,冀玉萍,等.神经病理性疼痛大鼠中脑导水管周围灰质腹外侧区GABAAα1受体的表达变化[J].解放军医学院学报,2018,62:173-176.
[11] Mauvais-Jarvis F,Arnold AP,Reue K.A guide for the design of pre-clinical studies on sex differences in metabolism [J].Cell Metab,2017,25:1216-1230.
[12] Paller CJ,Campbell CM,Edwards RR,et al.Sex-based differences in pain perception and treatment [J].Pain Med,2009,10:289-299.
[13] Tonsfeldt KJ,Suchland KL,Beeson KA,et al.Sex differences in GABAA signaling in the periaqueductal gray induced by persistent inflammation [J].J Neurosci,2016,36:1669-1681.
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