Spinal nerve lesion-induced mechanoallodynia and adrenergic sprouting in 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 system. It also results in novel adrenergic sympathetic innervation of the dorsal root ganglion (DRG) with the formation of pericellular axonal basket structures around some DRG neurons. Since the sympathetic sprouting and basket formation may represent an anatomical basis for pain-generating interactions between the sympathetic efferent neurons and sensory afferent neurons, it is of great interest to determine possible 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 have now investigated a possible contributory role of the pleiotropic cytokine interleukin-6 (IL-6) in sympathetically-mediated pain: we gave IL-6 knockout mice and mice of the parent strain c57B6/129 a SNL, assessed their resulting pain behavior for 10 days post-surgery, and used tyrosine-hydroxylase immunohistochemistry to compare sympathetic sprouting in the DRG at the end of the testing period. We found that thermal allodynia (as assessed by measuring the latency to withdrawal from radiant heat) did not differ significantly between strains. On the other hand, in the IL-6 mice, mechanoallodynia (as assessed with von Frey filaments) was markedly delayed. Sympathetic invasion of the fiber tract and cell layer of the DRG, and the formation of pericellular axonal baskets were all significantly reduced in the IL-6 knockout mice compared to the control strain. These results imply a facilitatory role for IL-6 in pain and sympathetic sprouting induced by nerve injury, and add to the growing list of roles for IL-6 in neuropathological events.
Ramer
Matt S
MS
Department of Physiology, Queen's University, Kingston, Ontario, K7L 3N6 Canada Division of Neurosurgery, McGill University and Montreal General Hospital, Montreal, Quebec, H3G 1A4 Canada.
Murphy
Patricia G
PG
Richardson
Peter M
PM
Bisby
Mark A
MA
D000818:Animals; D005260:Female; D017950:Ganglia, Sensory / Q000503:physiopathology*; D005728:Ganglia, Sympathetic / Q000503:physiopathology*; D006930:Hyperalgesia / Q000209:etiology* / Q000503:physiopathology; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009416:Nerve Regeneration / Q000502:physiology*; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000150:complications* / Q000503:physiopathology; D013127:Spinal Nerves; D013314:Stress, Mechanical; D013564:Sympathetic Nervous System
D015850:Interleukin-6