Contribution of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 to sensory transmission and nociceptive behavior.
The transmission of pain signals after injury or inflammation depends in part on increased excitability of primary sensory neurons. Nociceptive neurons express multiple subtypes of voltage-gated sodium channels (NaV1s), each of which possesses unique features that may influence primary afferent excitability. Here, we examined the contribution of NaV1.9 to nociceptive signaling by studying the electrophysiological and behavioral phenotypes of mice with a disruption of the SCN11A gene, which encodes NaV1.9. Our results confirm that NaV1.9 underlies the persistent tetrodotoxin-resistant current in small-diameter dorsal root ganglion neurons but suggest that this current contributes little to mechanical thermal responsiveness in the absence of injury or to mechanical hypersensitivity after nerve injury or inflammation. However, the expression of NaV1.9 contributes to the persistent thermal hypersensitivity and spontaneous pain behavior after peripheral inflammation. These results suggest that inflammatory mediators modify the function of NaV1.9 to maintain inflammation-induced hyperalgesia.
Priest
Birgit T
BT
Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065.
Murphy
Beth A
BA
Lindia
Jill A
JA
Diaz
Carmen
C
Abbadie
Catherine
C
Ritter
Amy M
AM
Liberator
Paul
P
Iyer
Leslie M
LM
Kash
Shera F
SF
Kohler
Martin G
MG
Kaczorowski
Gregory J
GJ
MacIntyre
D Euan
DE
Martin
William J
WJ
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D005786:Gene Expression Regulation; D006930:Hyperalgesia / Q000188:drug therapy; D007249:Inflammation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008957:Models, Genetic; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism / Q000502:physiology*; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012964:Sodium / Q000737:chemistry; D015222:Sodium Channels / Q000378:metabolism / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology*
D000779:Anesthetics, Local; D017931:DNA Primers; D018076:DNA, Complementary; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C491885:Scn11a protein, mouse; C113705:Scn11a protein, rat; D015222:Sodium Channels; D013779:Tetrodotoxin; D012964:Sodium