远位触液神经元15-HT1A受体在大鼠神经病理性痛中的作用

Role of 5-HT1A receptor in distal cerebrespinal fluid-contacting neurons in neuropathic pain in rats

目的评价远位触液神经元5-羟色胺1A（5-HT1A）受体在大鼠神经病理性痛中的作用。方法雄性SD大鼠40只，体重230～271）g，采用随机数字表法，将其随机分为4组（n=10）：假手术组（S组）、神经病理性痛组（NP组）、二甲基亚砜组（DMSO组）和8-羟基-2-（双-正丙胺基）．四氢萘满组（8-OH—DPAT组）。采用坐骨神经慢性压迫法（CCI）制备大鼠神经病理性痛模型，S组仅暴露坐骨神经，但不结扎。CCI后第7天，8-OH—DPAT组：阳DMSO组向远位触液神经元分别缓慢注射5-HT，A受体特异性激动剂8-OH—DPAT或DMSO1td，5rain内注射完毕。分别于CCI前（T0）、CCI后第7天（T1）和给药后3、6h（T2，3）时，测定缩足潜伏期（PWL）和缩足阈值（PWT）。于给药后6h时处死大鼠，取脑组织，采用免疫荧光标记法检测远位触液核神经元5-HT1A受体的表达。结果与S组比较，NP组、DMSO组和8-OH—DPAT组E时PWL缩短，PWT降低（P〈0．01）；与DMSO组比较，8-OH-DPAT组T2和L时PWL延长，PWT升高（P〈0．01）。与S组比较，NP组和DMSO组5-HT1A受体表达下调（P〈0．01）；与NP组和DMSO组比较，8-OH-DPAT组5-HT1A受体表达上调（P〈0．01）；NP组和DMSO组间5-HT1A受体表达比较差异无统计学意义（P〉0．05）。结论远位触液神经元5-HT1A受体参与了大鼠神经病理性痛的调控。

Objective To evaluate the role of 5-HT1A receptors in distal cerebrospinal fluid （CSF）-contacting neurons in neuropathie pain （NP） in rats. Methods Forty male SD rats weighing 230-270 g were randomly divided into 4 groups （n = 8 each）： sham operation group （group S）; NP group; dimethyl stdfoxide （DMSO） group and 8-OH-DPAT （a specific 5-HT1A receptor agonist） group. NP was induced by chronic constrictive injury （CCI） in groups NP, DMSO and 8-OH-DPAT. Four silk ligatures were placed on the sciatic nerve at 1 mm intervals. In group S, the sciatic nerve was exposed but not ligated. 8-OH-DPAT and DMSO 1μl were injected into the region where most of CSF-eontacting neurons are present over 5 min on 7th day after CCI in groups 8-OH-DPAT and DMSO respectively. Paw withdrawal latency （PWL） and paw withdrawal threshold （PWT） were measured before CCI, on 7th day after CCI, and at 3 and 6h after administration. The rats were sacrificed 6h after administration, and the brain tissues removed for deterrnination of the expression of 5-HTIA receptors in the distal CSF-contacting neurons by immunofluorescence. Rcsulls Compared with group S, PWL was significantly shorten and PWT decreased at T1 in groups NP, DMSO and 8-CH-DPAT （ P 〈 0.01）. Compared with group DMSO, PWL was significandy prolonged and PWT increased at T2 and T3 in group 8-OH-DPAT （ P 〈 0.01 ）. The 5-HT1A receptor expression was significantly down-regulated in groups NP and DMSO compared with group S, while up-regulated in group 8-OH-DPAT compared with groups NP and DMSO （ P 〈 0.01 ）. There was no significant difference in 5- HTIA receptor expression between groups NP and DMSO （ P 〉 0.05 ）. Conclusion 5-HT1A receptors in distal CSF-contacting neurons are involved in the regulation of NP in rats.