Regulation of TRPV2 by axotomy in sympathetic, but not sensory neurons.
Neuropathic pain results from traumatic or disease-related insults to the nervous system. Mechanisms that have been postulated to underlie peripheral neuropathy commonly implicate afferent neurons that have been damaged but still project centrally to the spinal cord, and/or intact neurons that interact with degenerating distal portions of the injured neurons. One pain state that is observed following peripheral nerve injury in the rat is thermal hyperalgesia. The noxious heat-gated ion channel TRPV1 may be responsible for this increased sensitivity, as it is up-regulated in L4 dorsal root ganglion (DRG) neurons following L5 spinal nerve lesion (SpNL). The TRPV1 homologue TRPV2 (or VRL-1) is another member of the TRPV subfamily of TRP ion channels. TRPV2 is a nonselective cation channel activated by high noxious temperatures (>52 degrees C) and is present in a subset of medium- to large-diameter DRG neurons. To establish whether TRPV2 is endogenous to the spinal cord, we examined its expression in the dorsal horn following rhizotomy. We found no significant decrease in TRPV2 immunoreactivity, suggesting that TRPV2 is endogenous to the spinal cord. In order to determine whether TRPV2, like TRPV1, is regulated by peripheral axotomy, we performed L5 SpNL and characterized TRPV2 distribution in the DRG, spinal cord, brainstem, and sympathetic ganglia. Our results show that peripheral axotomy did not regulate TRPV2 in the DRG, spinal cord, or brainstem; however, TRPV2 was up-regulated in sympathetic postganglionic neurons following injury, suggesting a potential role for TRPV2 in sympathetically mediated neuropathic pain.
Gaudet
Andrew D
AD
Department of Zoology, International Collaboration on Repair Discoveries (ICORD), University of British Columbia, 2469-6270 University Boulevard, Vancouver, BC, Canada V6T 1Z4.
Williams
Sarah J
SJ
Hwi
Lucy P-R
LP
Ramer
Matt S
MS
D000818:Animals; D019771:Axotomy; D015220:Calcium Channels / Q000378:metabolism*; D048429:Cell Size / Q000502:physiology; D005727:Ganglia, Spinal / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009475:Neurons, Afferent / Q000145:classification / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000378:metabolism*; D050052:TRPC Cation Channels
D015220:Calcium Channels; D009478:Neuropeptide Y; D050052:TRPC Cation Channels