Contribution of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 to sensory transmission and nociceptive behavior

BT Priest, BA Murphy, JA Lindia… - Proceedings of the …, 2005 - National Acad Sciences
BT Priest, BA Murphy, JA Lindia, C Diaz, C Abbadie, AM Ritter, P Liberator, LM Iyer, SF Kash…
Proceedings of the National Academy of Sciences, 2005National Acad Sciences
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 …
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.
National Acad Sciences