Levine J D, Moskowitz M A, Basbaum A I
J Immunol. 1985 Aug;135(2 Suppl):843s-847s.
The release of the peptide neurotransmitter substance P from the peripheral terminals of nociceptive afferent neurons and the release of catecholamines from postganglionic sympathetic efferent neurons produce physiologic changes associated with acute inflammation. The contribution of these neurogenic mechanisms to inflammatory diseases has not been determined. Activation of central neural circuits elicits similar physiologic changes, and lesions of the peripheral and central nervous system are associated with alteration in activity of inflammatory diseases. We have evaluated the contribution of neurogenic inflammation to the severity of joint injury in experimentally induced arthritis in the rat. The finding of a greater density of substance P-containing nociceptive afferents in a joint that develops more severe arthritis (ankle) suggests a role of substance P in joint injury. Direct evidence that the proinflammatory factor released from these nociceptors is substance P is provided by the finding that the injection of substance P into a joint which normally develops less severe arthritis (knee) increases the severity of arthritis in that joint. A contribution of catecholamines to the severity of joint injury was suggested by the finding that both guanethidine-induced sympathectomy and reserpine-induced depletion of catecholamines attenuated the severity of joint injury. Finally, a contribution of central neural circuits to inflammatory processes was studied in a model in which activation of nociceptive afferents elicited swelling and tenderness at a remote site. This reflex neurogenic inflammation was inhibited by intracerebroventricular injections of morphine, which also attenuated the severity of arthritis. These studies provide evidence that elements of the peripheral afferent and sympathetic efferent neurons and of descending supraspinal, opioid-mediated, circuits in the central nervous system modulate the severity of joint injury in experimental arthritis in the rat.
伤害性传入神经元外周终末释放肽类神经递质P物质，节后交感传出神经元释放儿茶酚胺，会产生与急性炎症相关的生理变化。这些神经源性机制对炎症性疾病的作用尚未确定。中枢神经回路的激活会引发类似的生理变化，而外周和中枢神经系统的损伤与炎症性疾病活动的改变有关。我们评估了神经源性炎症对大鼠实验性诱导关节炎中关节损伤严重程度的作用。在发生更严重关节炎的关节（踝关节）中，含P物质的伤害性传入纤维密度更高，这一发现表明P物质在关节损伤中发挥作用。将P物质注入通常发生不太严重关节炎的关节（膝关节）会增加该关节的关节炎严重程度，这一发现提供了直接证据，证明这些伤害感受器释放的促炎因子是P物质。胍乙啶诱导的交感神经切除术和利血平诱导的儿茶酚胺耗竭均减轻了关节损伤的严重程度，这一发现提示儿茶酚胺对关节损伤严重程度有作用。最后，在一个模型中研究了中枢神经回路对炎症过程的作用，在该模型中，伤害性传入纤维的激活会在远处部位引发肿胀和压痛。脑室内注射吗啡可抑制这种反射性神经源性炎症，同时也减轻了关节炎的严重程度。这些研究提供了证据，表明外周传入神经元、交感传出神经元以及中枢神经系统中下行的脊髓上阿片类介导回路的组成部分，可调节大鼠实验性关节炎中关节损伤的严重程度。
