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

作者以多发性关节炎大鼠为慢性疼痛模型，观察了参与脊髓背角伤害性传递的神经肽P物质在大鼠体内的周转变化及止痛剂对其的影响。1)多发性关节炎大鼠L4、L5背根节内免疫反应物质P含量显著高于对照组。2)应用轴突血流阻断剂秋水仙碱可进一步增加多发性关节炎大鼠背根神经节内isp的含量，但对对照组大鼠无明显影响。3)多发性关节炎大鼠脊髓背角的isp自发释放增加。4)全身应用抑制背角isp释放的吗啡仅增加多发性关节炎大鼠背角的isp含量。这些结果表明，多发性关节炎大鼠的P物质生物合成、轴突流动和初级传入终末释放增加，吗啡抑制P物质的释放。5)鞘内注射降钙素基因相关肽(CGRP)可产生对机械伤害性刺激的痛敏反应。但后者的痛觉过敏程度大于前者。降钙素基因相关肽的这种作用被P物质拮抗剂抑制。这些结果提示CGRP参与了慢性痛在大鼠脊髓背角的传递。

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.