鞘内注射氟代柠檬酸对炎性痛敏大鼠的镇痛作用

目的研究鞘内注射氟代柠檬酸(fluorocitrate,Fc)对致炎大鼠痛觉过敏的影响。方法采用大鼠右后爪踝关节外侧皮下注射完全弗氏佐剂(complete freunds adjuvant,CFA)50μl致炎模型。测定给予CFA或Fc前后大鼠机械性缩爪阈值(MWT)和热刺激缩爪潜伏期(TWL)。免疫组化分析脊髓背角星形胶质细胞标记物(GFAP)和小胶质细胞标记物(OX-42)的表达。结果大鼠皮下注射CFA24h后出现明显的炎性痛敏,鞘内注射Fc后4,6,8,10,12h,与CFA组大鼠比较,大鼠MWT明显提高(P<0.01),TWL明显延长(P<0.01)。鞘内注射Fc6h后,降低脊髓背角GFAP和OX-42表达。结论脊髓胶质细胞可能参与炎性痛敏的发生和维持,氟代柠檬酸可能通过抑制其生物活性而发挥镇痛作用。

The antinociceptive effect of intrathecal administration of fluorocitrate in a rat model of inflammatory pain

Aim To investigate the effect of intrathecal injection of fluorocitrate(Fc)on mechanical and thermal hyperalgesia induced by complete Freund's adjuvant(CFA)injection in rats.Methods The mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)were measured before and after CFA or Fc treatment.The changes of glial fibrillary acidic protein(GFAP)and OX-42(a microglial marker)expression in the spinal cord dorsal horn were evaluated by immunohistochemistry analysis.Results Rats with CFA-induced arthritis showed mechanical allodynia and thermal hyperalgesia,which was correlated with the increased GFAP and OX-42 expression in the spinal cord dorsal horn.Intrathecal injection of Fc markedly suppressed CFA-induced thermal hyperalgesia and mechanical allodynia.Fc significantly attenuated the activation of GFAP and OX-42 in the spinal cord dorsal horn.Conclusions The glia activation in spinal cord is closely related to the progress of CFA-induced peripheral hyperalgesia.Fc may exert antihyperalgesic effect by inhibiting the activation of astrocyte and microglia.