α2肾上腺素受体亚型对神经病理性疼痛大鼠镇痛作用的电生理研究

THE ELECTROPHYSIOLOGICAL MECHANISM UNDERLYING ANALGESIC EFFECTS OF Alpha-2 ADRENOCEPTOR SUBTYPES ON NEUROPATHIC RATS

目的:研究α2肾上腺素受体(α2-adrenoceptors,α2-AR)不同亚型在神经病理性疼痛中的作用及其可能机制。方法:成年SD大鼠行保留性脊神经损伤手术(Spared Nerve Injury,SNI),术后14天测缩足阈值(Paw withdrawal threshold,PWT),以PWT≤4 g为造模成功。通过胞外电生理记录的方法,脊髓表面给予α2-AR三个不同亚型(α2A-AR,α2B-AR,α2C-AR)激动剂和拮抗剂,观察其对脊髓背角广动力范围神经元(wide-dynamic range neurons,WDR)诱发放电影响。通过连续鞘内给药方法,进一步验证α2-AR特定亚型激动剂对SNI大鼠50%PWT的影响。结果:(1)α2A-AR激动剂可以显著地抑制WDR神经元的诱发放电(P<0.01,n=10),而α2A-AR拮抗剂能够逆转这种作用。(2)α2B-AR拮抗剂、α2C-AR激动剂和α2C-AR拮抗剂对WDR神经元的诱发放电均无明显的影响(P>0.05,n=9)。(3)鞘内给予α2A-AR激动剂可以显著的提高SNI神经病理性痛大鼠50%PWT。结论:α2-AR激动剂在神经病理性疼痛大鼠脊髓水平的镇痛作用可能主要是通过激动α2A-AR而实现的。

Objective：To investigate the mechanism of analgesic effects of alpha-2 adrenoceptor subtypes on neuropathic pain.Methods：The 50％ Paw withdrawal thresholds （50％ PWT） were measured on six weeks old SD rats which received SNI surgery previously.PWT ≤ 4g was considered modeling successful.Through the extracellular electrophysiological recording method,the effects of agonists and antagonists of the three different subtypes of α 2-AR on the wide dynamic range （WDR） neuron of spinal cord dorsal horn were observed.The in vivo effects of α 2-AR subtype agonist on SNI rats＇ pain threshold （50％ PWT） were tested via intrathecal administration.Results：（1） α 2A-AR agonist could significantly suppress the evoked discharge of WDR neurons （P ＜ 0.01,n =10）,this effect could be reversed by α 2A-AR antagonist subsequently.（2） There were no significant effects of α 2B-AR antagonist,oα 2C-AR agonist and α 2C-AR antagonist on evoked discharge of WDR neurons were recorded （P ＞ 0.05,n =9）.（3） Intrathecal administration of α 2A-AR agonist could significantly increase the 50％ PWT on SNI rats.Conclusion：These findings suggested that α 2-AR agonist＇s analgesic effects on neuropathic pain mainly acted by α 2-AR in rats＇ spinal cord dorsal horn.