Regulation of expression of the sensory neuron-specific sodium channel SNS in inflammatory and neuropathic pain.
Increased voltage-gated sodium channel activity may contribute to the hyperexcitability of sensory neurons in inflammatory and neuropathic pain states. We examined the levels of the transcript encoding the tetrodotoxin-resistant sodium channel SNS in dorsal root ganglion neurons in a range of inflammatory and neuropathic pain models in the rat. Local Freund's adjuvant or systemic nerve growth factor-induced inflammation did not substantially alter the total levels of SNS mRNA. When NGF-treated adult rat DRG neurons in vitro were compared with NGF-depleted control neurons, SNS total mRNA levels and the levels of membrane-associated immunoreactive SNS showed a small increase (17 and 25%, respectively), while CGRP levels increased fourfold. SNS expression is thus little dependent on NGF even though SNS transcript levels dropped by more than 60% 7-14 days after axotomy. In the streptozotocin diabetic rat SNS levels fell 25%, while in several manipulations of the L5/6 tight nerve ligation rat neuropathic pain model, SNS levels fell 40-80% in rat strains that are either susceptible or relatively resistant to the development of allodynia. Increased expression of SNS mRNA is thus unlikely to underlie sensory neuron hyperexcitability associated with inflammation, while lowered SNS transcript levels are associated with peripheral nerve damage.
Okuse
K
K
Department of Biology, University College, London, United Kingdom.
Chaplan
S R
SR
McMahon
S B
SB
Luo
Z D
ZD
Calcutt
N A
NA
Scott
B P
BP
Akopian
A N
AN
Wood
J N
JN
D000818:Animals; D019771:Axotomy; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D007279:Injections, Subcutaneous; D008026:Ligation; D008297:Male; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000494:pharmacology; D009475:Neurons, Afferent / Q000378:metabolism*; D010146:Pain / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015222:Sodium Channels / Q000096:biosynthesis* / Q000235:genetics; D013127:Spinal Nerves / Q000502:physiology; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics
D062559:NAV1.8 Voltage-Gated Sodium Channel; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C568319:Scn10a protein, rat; D015222:Sodium Channels; D005620:Freund's Adjuvant