SPINAL NERVE LESION-INDUCED MECHANOALLODYNIA AND ADRENERGIC SPROUTINGIN SENSORY GANGLIA ARE ATTENUATED IN INTERLEUKIN-6 KNOCKOUT MICE

Tight ligation and transection of the L5 spinal nerve (SNL) gives rise to pain which is dependent upon activity in the sympathetic nervous s ystem. It also results in novel adrenergic sympathetic innervation of the dorsal root ganglion (DRC) with the formation of pericellular axon al basket structures around some DRG neurons. Since the sympathetic sp routing and basket formation may represent an anatomical basis for pai n-generating interactions between the sympathetic efferent neurons and sensory afferent neurons, it is of great interest to determine possib le chemical mediators of this phenomenon. Previous findings have shown that IL-6 can contribute to sympathetically-independent pain, and can give rise to thermal hyperalgesia when injected intrathecally. We hav e now investigated a possible contributory role of the pleiotropic cyt okine interleukin-6 (IL-6) in sympathetically-mediated pain: we gave I L-6 knockout mice and mice of the parent strain c57B6/129 a SNL, asses sed their resulting pain behavior for 10 days post-surgery, and used t yrosine-hydroxylase immunohistochemistry to compare sympathetic sprout ing in the DRG at the end of the resting period. We found that thermal allodynia (as assessed by measuring the latency to withdrawal from ra diant heat) did not differ significantly between strains. On the other hand, in the IL-6 mice, mechanoallodynia (as assessed with von Frey f ilaments) was markedly delayed. Sympathetic invasion of the fiber trac t and cell layer of the DRG, and the formation of pericellular axonal baskets were all significantly reduced in the IL-6 knockout mice compa red to the control strain. These results imply a facilitatory role for IL-6 in pain and sympathetic sprouting induced by nerve injury, and a dd to the growing list of roles for IL-6 in neuropathological events. (C) 1998 International Association for the Study of Pain. Published by Elsevier Science B.V.