Turnover changes of neuropeptide with chronic pain and its alteration by analgesics

我使用多关节炎大鼠作为慢性疼痛模型，并揭示了以下关于神经肽P物质的转换变化的观点，P物质参与脊髓背角的伤害性传递，结果：（1）大鼠海马神经元内P物质（iSP）含量明显增高，在L4和L5背根神经节中，多发性关节炎大鼠显著高于对照组大鼠。2）用轴突流阻断剂秋水仙碱治疗后，多发性关节炎大鼠背根神经节内iSP含量进一步增加，3）多发性关节炎大鼠脊髓背角iSP的自发释放增强。吗啡抑制脊髓背角iSP的释放，但仅在多发性关节炎大鼠脊髓背角增加iSP的含量。结果表明，多发性关节炎大鼠P物质的生物合成、轴突流动和初级传入终末的释放均增强，吗啡抑制P物质的释放。5）鞘内注射降钙素基因相关肽（CGRP）可使对照组和多发性关节炎大鼠对机械伤害性刺激产生痛觉过敏。但后者的痛觉过敏程度大于前者。CGRP的这种作用可被P物质拮抗剂所抑制。这些结果表明CGRP参与了大鼠脊髓背角慢性疼痛的传递。

I used polyarthritic rats as a model of chronic pain and reveaied the following points concerning the turnover change of a neuropeptide, substance P, which is involved in nociceptive transmission in the spinal dorsal horn, in the rats and an influence of an analgesic on the change.1) The content of immunoreactive substance P (iSP) in the dorsal root ganglia of L4 and L5 was significantly higher in polyarthritic rats than in control rats. On the contrary, that in the dorsal horn was lower in the former than in the latter.2) The treatment with colchicine, a blocker of axonal flow, produced a further increase in the content of iSP in the dorsal root ganglia of polyarthritic rats, but did not significantly change that of control rats.3) The spontaneous release of iSP from the spinal dorsal horn was enhanced in polyarthritic rats.4) Systemic administration of morphine which inhibits the release of iSP from the dorsal horn increased the content of iSP in the dorsal horn only in polyarthritic ratrs. These findings suggest that the biosynthesis, axonal flow and release from the primary afferent terminals of substance P are enhanced in polyarthritic arts, and that morphine inhibits the release of substance P.5) Intrathecal injection of calcitonin gene-related peptide (CGRP) produced a hyoperalgesia to mechanical noxious stimuli in control and polyarthritic rats. But the degree of the hyperalgesia was larger in the latter than in the former. Such an effect of CGRP was inhibited by a substance P antagonist. These results suggest an involvement of CGRP in the transmission of chronic pain in the rat spinal dorsal horn.