We used pharmacological and surgical methods to determine the contribution of several neural components to joint injury in rats with adjuvant-induced arthritis. Both neonatal administration of capsaicin, which eliminates small-diameter afferents, and peripheral sympathectomy, which depletes catecholamines, attenuated joint injury. In contrast, the arthritis was more severe in spontaneously hypertensive rats, which have increased sympathetic tone. To address the contribution of the central vs peripheral afferent terminal selectively, a group of rats underwent unilateral dorsal rhizotomy. These rats developed a more severe arthritis in the deafferented limb. The increase in arthritis severity produced by dorsal rhizotomy could be reduced by prior sympathectomy or, less effectively, by prior treatment with capsaicin. The latter observation suggests that large-diameter afferents that are cut during dorsal rhizotomy also influence inflammation. Finally, intracerebroventricular injection of morphine attenuated the severity of arthritis, possibly through activation of bulbospinal sympathoinhibitory circuits. Taken together, these data indicate that no one class of nerve fiber is wholly responsible for the neurogenic component of inflammation in experimental arthritis but that large- and small-diameter afferents, sympathetic efferents, and CNS circuits that modulate those fiber systems all influence the severity of joint injury in arthritic rats.

Recent studies of the mechanism of neurogenic inflammation have focused on the contribution of neuropeptides released from peripheral terminals of primary afferent sensory neurons. In this study we addressed the contribution of humoral and neural factors to the hyperalgesia and swelling that are produced contralateral to an injured hindpaw, a phenomenon which we refer to as reflex neurogenic inflammation. The contralateral inflammatory response develops gradually, over a period of hours, and shows no tachyphylaxis with repeated application of the same stimulus. Denervation of either limb significantly attenuated the contralateral responses. Selective lesions of small-diameter, presumed nociceptive afferent fibers with capsaicin, or of sympathetic postganglionic efferents by immunosympathectomy, also reduced swelling and hyperalgesia of the uninjured paw. Interruption of venous circulation to the injured limb by vein ligation did not alter the response in the contralateral paw. Taken together, these data suggest that reflex neurogenic inflammation is neurally mediated, via connections across the spinal cord.