Differences in sympathetic innervation of mouse DRG following proximal or distal nerve lesions.
Nerve injury leads to novel sympathetic innervation of the dorsal root ganglion (DRG). We have hypothesized previously that the degenerating nerve increases the sympathetic sprouting in the DRG and pain after chronic sciatic constriction injury (CCI) by virtue of its influence on sensory and sympathetic axons spared by the injury. However, L5 spinal nerve ligation and transection (SNL) results in the complete isolation of the L5 DRG from the degenerating stump, yet sympathetic axons invade the ganglion, and sympathetically dependent pain develops. We investigated the role of Wallerian degeneration in both sympathetic sprouting and neuropathic pain in these two models of painful peripheral neuropathy by comparing responses of normal C57B1/6J and C57B1/Wlds mice in which degeneration is impaired. After CCI, Wlds mice, unlike 6J mice, did not develop thermal or mechanoallodynia or sympathetic innervation of the L5 DRG. After SNL, both strains developed mechanoallodynia and sympathetic sprouts in L5, but only 6J mice developed thermal allodynia. Observation of the origins of the invading sympathetic axons revealed that after CCI, sympathetics innervating blood vessels and dura (probably intact) sprouted into the ganglion, but after SNL sympathetics (probably axotomized) invaded from the injured spinal nerve. Based on these findings, we hypothesize that there are two mechanisms for sympathetic sprouting into DRG, differentially dependent on Wallerian degeneration. Analysis of pain behavior in these animals reveals that (i) mechanoallodynia and sympathetic innervation of the DRG tend to coincide and (ii) thermal allodynia and Wallerian degeneration, but not sympathetic innervation of the DRG tend to coincide.
Department of Physiology, Queen's University, Kingston, Ontario, K7L 3N6, Canada.
M S
MS
Ramer
M A
MA
Bisby
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003250:Constriction; D005727:Ganglia, Spinal / Q000293:injuries*; D006651:Histocytochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000503:physiopathology*; D017288:Pain Threshold; D013314:Stress, Mechanical; D013564:Sympathetic Nervous System / Q000293:injuries*; D013696:Temperature; D014855:Wallerian Degeneration