鞘内应用普瑞巴林对神经病理性疼痛大鼠的镇痛作用及其电生理学机制研究

ANALGESIC EFFECTS OF INTRATHECAL ADMINISTRATION OF PREGABALIN ON NEUROPATHIC PAIN IN RATS: STUDY ON THE ELECTROPHYSIOLOGICAL MECHANISMS

目的:研究鞘内应用普瑞巴林(pregabalin,PGB),一种新型抗癫痫药,对神经病理性疼痛大鼠的镇痛作用及其可能的机制。方法:(1)雄性SD大鼠鞘内置管,手术成功后进行坐骨神经分支选择性损伤(spared nerve injury,SNI)手术。术后10 d用von Frey纤维丝测定机械痛敏,将筛选出造模成功的SNI神经病理性疼痛大鼠,按体重随机分为两组(n=10),通过鞘内插管分别鞘内给予(i.t.)普瑞巴林100μg/d或等体积的生理盐水(saline,NS)作阴性对照,连续3 d给药。在每次给药后24 h测定大鼠后爪的50%缩足阈值(paw withdrawal threshold,PWT)及鞘内给药前后大鼠的运动功能。(2)通过在体细胞外记录的电生理学方法,观察脊髓背表面给予普瑞巴林100μg对SNI大鼠脊髓背角广动力范围,(wide dynamic range,WDR)神经元C纤维诱发放电的影响。结果:(1)与NS组相比,鞘内应用普瑞巴林100μg/d,连用3 d,能显著增加SNI大鼠术侧后爪的50%PWT,起到显著的镇痛作用(P<0.001,n=10),给药前后大鼠的运动功能没有明显改变(P>0.05,n=10)。(2)与NS组相比,脊髓背表面给予普瑞巴林100μg可以显著抑制SNI大鼠WDR神经元的C纤维诱发放电(P<0.001,n=9)。结论:鞘内应用普瑞巴林100μg/d可以对SNI大鼠产生显著的镇痛作用而不影响其运动功能,该机制可能与通过WDR神经元的C纤维诱发放电有关。

Objective： To investigate the potential mechanisms and the analgesic effects of intrathecal（i.t.）administration of pregabalin,an antiepileptic drug,on rats with neuropathic pain.Methods：（1） Spared nerve injury（SNI） was established after intrathecal catheterizations were successfully made in male Sprague-Dawley rats.The mechanical allodynia was determined with von Frey filaments at 10 days after the SNI surgery.The SNI rats with neuropathic pain were randomly divided into two groups.Pregabalin（100 μg/d,i.e.） or equal volume of normal saline as the negative control was intrathecally administrated in each group for three consecutive days.The 50% paw withdrawal threshold（PWT） of the rats were tested with von Frey flaments at 24 h after pregabalin or normal saline administration.The locomotor function was also examined by a slope board test at the same time points.（2） The effects of pregabalin on the C-fber induced discharge of spinal wide dynamic range（WDR） neurons were examined through extracellular electrophysiological recording in vivo in SNI rats.Results：（1） Intrathecal injection of pregabalin（100 μg） produced signifcant increase in 50%PWT（P 0.001,n = 10）,the analgetic effect was signifcant.Moreover,no obvious impairment on locomotor function was observed after i.t.injection of pregabalin at the dose of 100 μg/d.（2） Spinal administration of pregabalin（100 μg） showed significant inhibition on C-fiber evoked discharges（P 0.001,n = 9）.Conclusion： Intrathecal injection of pregabalin（100 μg/50 μl） had signifcant analgesic effects on neuropathic pain in rats,and did not affect their locomotor function.It is likely that such analgesic effects were achieved via inhibiting the C-fber evoked discharges of spinal WDR neurons.