炎性痛-吗啡耐受大鼠背根神经节辣椒素受体磷酸化水平的变化

Change in the phosphorylation of vanilloid receptor 1 in dorsal root ganglion in rats with inflammatory pain- morphine tolerance

目的 探讨炎性痛-吗啡耐受大鼠背根神经节辣椒素受体（VR1）磷酸化水平的变化.方法 鞘内置管成功的成年雄性SD大鼠20只,体重230～250 g,2～3月龄,采用左后足踝关节腔注射完全弗氏佐剂（CFA）50μl的方法制备炎性痛模型.大鼠随机分为4组（n=5）,炎性痛＋生理盐水组（NS组）：注射剂CFA后3 d鞘内注射生理盐水10μl,2次/d,连续7 d;单纯吗啡组（M0组）：不建立炎性痛模型,鞘内注射吗啡10μl/kg,2次/d,连续7 d;炎性痛＋单次吗啡组（M1组）：注射CFA后3 d鞘内注射吗啡10μl/kg;炎性痛＋连续吗啡组（M2组）：注射CFA后3 d鞘内注射吗啡10 μg/kg,2次/d,连续7 d.于鞘内置管后、注射CFA后3 d鞘内给药前、给药1～7 d测定机械缩足反射阈值和缩足潜伏期,最后一次测定痛阈后处死大鼠,采用Western blot法测定背根神经节磷酸化VR1（p-VR1）的表达水平.结果 NS组和M1组未发生吗啡耐受,M0组和M2组发生吗啡耐受.4组中,M2组背根神经节p-VR1表达水平最高（P＜0.05）.结论炎性痛-吗啡耐受大鼠背根神经节VR1磷酸化水平升高,该变化可能是吗啡耐受形成的机制.

Objective To investigate the change in the phosphorylation of vanilloid receptor 1 （VR1） in dorsal root ganglion （DRG） in rats with inflammatory pain （IP）-morphine tolerance. Methods Twenty 8-12 months old male SD rats in which intrathecal （IT） catheters were successfully implanted without complication were randomly divided into 4 groups （n =5 each）： group NS, IP ＋ normal saline （NS） 10 μl IT twice a day ×7 days; group M0 ,intact rats ＋ morphine 10 μg/kg （ 10 μl） IT twice a day × 7 days; group M1 , IP ＋ morphine 10 μg/kg （10 μl） IT once; group M2 ,IP ＋ morphine 10 μg/kg（10 μl） IT twice a day × 7 days. IP was induced by injecting complete Freund＇s adjuvant （CFA） into the ankle joint of the left hindlimb. IT morphine or NS was started on the 3rd day after induction of IP. Paw withdrawal threshold （PWT） and paw withdrawal latency （PWL）were measured after catheterization, before and at 1-7 days of IT consecutive administration. The rats were sacrificed after last pain threshold measurement. The phosphorylated VR1 （p-VR1） protein expression in DRG was determined by Western blot. Results There was no significant difference in the baseline PWL measured before induction of IP among the 4 groups. Morphine tolerance developed in group M0 and M2. The expression of p-VR1 in DRG was highest in group M2. Conclusion The phosphorylation of VR1 in DRG in rats with IP tolerance is increased, which is involved in the development of morphine tolerance.