神经病理性痛大鼠杏仁核神经肽S与脊髓背角5-HT和GABA的关系

Relationship between neuropeptide S in amygdala and 5-hydroxytryptamine and GABA in spinal dorsal horns of rats with neuropathic pain

目的评价神经病理性痛大鼠杏仁核神经肽S（NPS）与脊髓背角5-羟色胺（5-HT）和GABA的关系。方法清洁级健康雄性SD大鼠80只，体重200～260 g，2月龄，采用随机数字表法分为4组（n＝20）：假手术组（Sham组）、神经病理性痛组（NP组）、NPS低剂量组（L-NPS组）和NPS高剂量组（H-NPS组）。采用左侧L5，6脊神经结扎（SNL）法制备神经病理性痛模型。L-NPS组和H-NPS组分别于SNL后3、6、9、12、15和18 d时双侧杏仁核注射NPS，L-NPS组每侧10 pmol、H-NPS组每侧100 pmol。于SNL前2 d、SNL后1、4、7、11、14、17和21 d时测定机械缩足反射阈（MWT）和热缩足潜伏期（TWL）。于SNL后7、14和21 d时取5只大鼠，采用荧光免疫组化法检测脊髓背角5-HT和GABA的表达。结果与Sham组比较，NP组、L-NPS组和H-NPS组MWT降低，TWL缩短，脊髓背角5-HT和GABA表达下调（P〈0.05）；与NP组比较，L-NPS组和H-NPS组MWT升高，TWL延长，脊髓背角5-HT和GABA表达上调（P〈0.05）；与L-NPS组比较，H-NPS组MWT升高，TWL延长，脊髓背角5-HT和GABA表达上调（P〈0.05）。结论大鼠神经病理性痛时杏仁核NPS内源性镇痛作用的脊髓机制可能与上调脊髓背角5-HT和GABA的表达有关。

Objective To evaluate the relationship between neuropeptide S （NPS） in the amygdala and 5-hydroxytryptamine （5-HT） and GABA in spinal dorsal horns of rats with neuropathic pain.Methods Eighty pathogen-free healthy male Sprague-Dawley rats, weighing 200-260 g, aged 2 months, were divided into 4 groups （n=20 each） using a random number table： sham operation group （group Sham）, neuropathic pain group （group NP）, low dose NPS group （group L-NPS） and high dose NPS group （group H-NPS）. The neuropathic pain model was established by left L5, 6 spinal nerve ligation （SNL） in anesthetized rats.NPS was injected into the bilateral amygdala at 3, 6, 9, 12, 15 and 18 days after SNL in L-NPS group （10 pmol per side） and H-NPS group （100 pmol per side）. The mechanical paw withdrawal threshold （MWT） and thermal paw withdrawal latency （TWL） were measured at 2 days before SNL and 1, 4, 7, 11, 14, 17 and 21 days after SNL.Five rats were selected at 7, 14 and 21 days after SNL and sacrificed, and the lumbar segment （L5） of the spinal cord was removed for detection of the expression of 5-HT and GABA in spinal dorsal horns by immunofluorescence histochemistry.Results Compared with group Sham, the MWT was significantly decreased, the TWL was shortened, and the expression of 5-HT and GABA in spinal dorsal horns was down-regulated in NP, L-NPS and H-NPS groups （P〈0.05）. Compared with group NP, the MWT was significantly increased, the TWL was prolonged, and the expression of 5-HT and GABA in spinal dorsal horns was up-regulated in L-NPS and H-NPS groups （P〈0.05）. Compared with group L-NPS, the MWT was significantly increased, the TWL was prolonged, and the expression of 5-HT and GABA in spinal dorsal horns was up-regulated in group H-NPS （P〈0.05）.Conclusion The spinal mechanism of endogenous analgesia induced by NPS in the amygdala may be related to up-regulation of the expression of 5-HT and GABA in spinal dorsal horns of rats with neuropathic pain.