Faculty Collaboration Database

Neurotrophin-3 significantly reduces sodium channel expression linked to neuropathic pain states. Exp Neurol 2008 Oct;213(2):303-14

Date

07/08/2008

Pubmed ID

18601922

Pubmed Central ID

PMC2751854

DOI

10.1016/j.expneurol.2008.06.002

Scopus ID

2-s2.0-51349109964 (requires institutional sign-in at Scopus site)   39 Citations

Abstract

Neuropathic pain resulting from chronic constriction injury (CCI) is critically linked to sensitization of peripheral nociceptors. Voltage gated sodium channels are major contributors to this state and their expression can be upregulated by nerve growth factor (NGF). We have previously demonstrated that neurotrophin-3 (NT-3) acts antagonistically to NGF in modulation of aspects of CCI-induced changes in trkA-associated nociceptor phenotype and thermal hyperalgesia. Thus, we hypothesized that exposure of neurons to increased levels of NT-3 would reduce expression of Na(v)1.8 and Na(v)1.9 in DRG neurons subject to CCI. In adult male rats, Na(v)1.8 and Na(v)1.9 mRNAs are expressed at high levels in predominantly small to medium size neurons. One week following CCI, there is reduced incidence of neurons expressing detectable Na(v)1.8 and Na(v)1.9 mRNA, but without a significant decline in mean level of neuronal expression, and similar findings observed immunohistochemically. There is also increased accumulation/redistribution of channel protein in the nerve most apparent proximal to the first constriction site. Intrathecal infusion of NT-3 significantly attenuates neuronal expression of Na(v)1.8 and Na(v)1.9 mRNA contralateral and most notably, ipsilateral to CCI, with a similar impact on relative protein expression at the level of the neuron and constricted nerve. We also observe reduced expression of the common neurotrophin receptor p75 in response to CCI that is not reversed by NT-3 in small to medium sized neurons and may confer an enhanced ability of NT-3 to signal via trkA, as has been previously shown in other cell types. These findings are consistent with an analgesic role for NT-3.

Author List

Wilson-Gerwing TD, Stucky CL, McComb GW, Verge VM

Author

Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Constriction
Down-Regulation
Ganglia, Spinal
Male
NAV1.8 Voltage-Gated Sodium Channel
NAV1.9 Voltage-Gated Sodium Channel
Nerve Tissue Proteins
Neuralgia
Neurons
Neuropeptides
Neurotrophin 3
RNA, Messenger
Rats
Rats, Wistar
Sodium Channels