Contribution of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 to sensory transmission and nociceptive behavior
Journal - PNAS
Accepted for publication May 5, 2005.
The transmission of pain signals after injury or inflammationdepends in part on increased excitability of primary sensoryneurons. Nociceptive neurons express multiple subtypes of voltage-gatedsodium channels (NaV1s), each of which possesses unique featuresthat may influence primary afferent excitability. Here, we examinedthe contribution of NaV1.9 to nociceptive signaling by studyingthe electrophysiological and behavioral phenotypes of mice witha disruption of the SCN11A gene, which encodes NaV1.9. Our resultsconfirm that NaV1.9 underlies the persistent tetrodotoxin-resistantcurrent in small-diameter dorsal root ganglion neurons but suggestthat this current contributes little to mechanical thermal responsivenessin the absence of injury or to mechanical hypersensitivity afternerve injury or inflammation. However, the expression of NaV1.9contributes to the persistent thermal hypersensitivity and spontaneouspain behavior after peripheral inflammation. These results suggestthat inflammatory mediators modify the function of NaV1.9 tomaintain inflammation-induced hyperalgesia.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: DRG, dorsal root ganglion; NaV1, voltage-gatedsodium channel; TTX, tetrodotoxin; IRES, internal ribosome entrysite; CFA, complete Freund's adjuvant; PGE2, prostaglandin E2.© 2005 by The National Academy of Sciences of the USA
|Keywords : ||hyperalgesia • pain • mouse • inflammation • C-fibers|