Reflex neurogenic inflammation. I. Contribution of the peripheral nervous system to spatially remote inflammatory responses that follow injury

Abstract

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.