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

我以多发性关节炎大鼠作为慢性疼痛模型，揭示了大鼠脊髓背角中参与伤害性传递的P物质神经肽的转换变化以及镇痛药对其变化的影响。1)多发性关节炎大鼠L4、L5背根神经节免疫反应性物质P （iSP）含量显著高于对照组。相反，前者在背角处比后者低。2)轴突血流阻滞剂秋水仙碱处理可使多发性关节炎大鼠背根神经节内iSP含量进一步升高，但与对照组相比无明显变化。3)多关节炎大鼠脊髓背角的iSP自发释放增强。4)全身注射吗啡，抑制多关节炎大鼠背角iSP的释放，仅增加多关节炎大鼠背角iSP的含量。这些结果提示，在多发性关节炎中P物质的生物合成、轴突流动和初级传入末端的释放增强，吗啡抑制P物质的释放。5)鞘内注射降钙素基因相关肽（CGRP）可使对照大鼠和多发性关节炎大鼠对机械有害刺激产生痛觉减退。但后者的痛觉过敏程度大于前者。CGRP的这种作用被P物质拮抗剂抑制。这些结果提示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.