大鼠脊髓环氧合酶在皮下注射蜜蜂毒诱发的持续性自发痛、原发性痛敏的发生和在脊髓c-fos蛋白表达中的作用

ROLES OF SPINAL CYCLOOXYGENASES IN THE DEVELOPMENT OF BEE VENOM INDUCED PERSISTENT SPONTANEOUS PAIN, PRIMARY HYPERALGESIA AND SPINAL c fos PROTEIN EXPRESSION IN THE RAT

本实验用鞘内给药的方法对非选择性环氧合酶 1/ 2抑制剂吲哚美辛 (indomethacin,Indo)和选择性环氧合酶 2抑制剂Etodolac对蜜蜂毒诱致的自发缩足行为、原发性 (热和机械性 )痛敏和脊髓背角 c-fos蛋白表达的效果进行了观察 ,发现 :(1)预先用吲哚美辛和 Etodolac处理均可剂量依赖性地抑制自发缩足行为的发生 ,提示脊髓环氧合酶 2 (但不能完全排除环氧合酶 1)在长时程、持续性自发痛的诱导中具有重要作用 ;(2 )与上述结果不同 ,预先用吲哚美辛和 Etodolac处理对蜜蜂毒注入部位热刺激潜伏期缩短和机械性刺激阈值的下降无抑制作用 ,提示脊髓环氧合酶在原发性热和机械痛敏的诱导不起任何作用 ;(3 )上述两种药物的同样处理对脊髓背角 c-fos蛋白的表达均具有显著抑制作用 ,但通过对背角浅、深层细胞分别记数分析显示两种环氧合酶抑制剂只对浅层具有抑制作用 ,而对深层则无。以上结果提示 ,脊髓环氧合酶参与介导蜜蜂毒组织损伤后持续性自发痛的发生 ,但不参与原发性热和机械性痛敏的发生 ;背角浅层 c-fos阳性神经元可能不参与介导原发性痛敏的发生。

By using intrathecal drug administration method, we observed the effects of indomethacin, a non selective COX (cyclooxygenases) 1/2 inhibitor and etodolac, a selective COX2 inhibitor on the bee venom (bv) induced persistent spontaneous flinching reflex, primary heat and mechanical hyperalgesia, and c Fos expression in the spinal cord of rats. We found that: (1) pre treatment with either indomethacin or etodolac could dose dependently suppress the spontaneous flinching reflex, suggesting that the spinal COX2 (but COX1 could not be completely excluded) plays an important role in induction of long lasting, persistent spontaneous pain; (2) unlike the above result, however, the same pre treatment with the two inhibitors did not show any suppressive effect on the reduction in heat latency and mechanical threshold, implicating that the spinal COX does not play any role in the induction of the bv induced primary heat and mechanical hyperalgesia; (3) the same pre treatment with the two drugs did suppress the expression of c Fos protein in the spinal dorsal horn, however, the two COX inhibitors only produced statistically significant suppressive effects on c Fos expression in the superficial layers (laminae I II) with no influence on that in the deep layers of the dorsal horn. Taken together, it is concluded that (1) spinal COX is involved in development of tissue injury induced spontaneous pain, but it is not involved in that of primary heat and mechanical hyperalgesia; (2) the c Fos expressing neurons in the superficial layers are not likely to be involved in development of primary hyperalgesia.