静脉或鞘内注射盐酸奈福泮对大鼠 甲醛炎性痛的影响及机制探讨

Effect of intrathecal or intravenous injection of Hydrochloride Nefopam on rat model of formalin induced pain

摘要:

目的 评估盐酸奈福泮静脉或鞘内注射的镇痛效果及脊髓多巴胺能神经传递在其中的作用。方法 复制大鼠甲醛炎性痛模型，然后进行微透析研究，检测盐酸奈福泮注射后大鼠脊髓背角细胞外多巴胺浓度变 化。通过预先注射舒必利，多巴胺D2 受体拮抗剂，观察多巴胺水平变化与盐酸奈福泮镇痛的关系。结果 静 脉注射盐酸奈福泮，可抑制甲醛诱导的Ⅰ期退缩反应，但对Ⅱ期退缩反应无影响。鞘内注射盐酸奈福泮可减 少Ⅰ和Ⅱ期退缩反应，并呈剂量依赖性。微透析研究发现，鞘内注射盐酸奈福泮引起大鼠脊髓多巴胺水平增加。 预处理舒必利不影响静脉或鞘内注射盐酸奈福泮的镇痛作用。结论 无论是静脉和鞘内注射盐酸奈福泮均有 效缓解大鼠炎性痛。盐酸奈福泮镇痛机制可能不涉及脊髓水平多巴胺能神经传递。

Abstract:

Objective To investigate the role of the spinal dopaminergic neurotransmission in Hydrochloride Nefopam mediated antinociceptive effect. Methods Rat model of formalin induced pain was established. Concentration of dopamine in spinal dorsal horn was measured after intravenous or intrathecal administration of Hydrochloride Nefopam. Pretreatment of Sulpiride, a dopaminergic D2 receptor antagonist, was performed to determine association of dopamine with Hydrochloride Nefopam mediated analgesia. Results Intravenous injection of Hydrochloride Nefopam inhibited the flinching responses in phase I but not in phase Ⅱ. Intrathecally injected Hydrochloride Nefopam reduced the flinching responses in both phase I and phase Ⅱ in a dose dependent manner. Micro-dialysis study revealed a significant increase of dopamine in the spinal cord by intrathecal administration of Hydrochloride Nefopam but not with intravenous injection. Analgesic effects of intrathecally injected Hydrochloride Nefopam was not affected by pretreatment with Sulpiride. Conclusions Administration of Hydrochloride Nefopam relieves inflammatory pain in rats; analgesic mechanism of Hydrochloride Nefopam may not involve the dopaminergic transmission at the spinal level.