Exploring the role of nociceptor-specific sodium channels in pain transmission using Nav1.8 and Nav1.9 knockout mice.
Two voltage gated sodium channels, Na(v)1.8 and Na(v)1.9, are exclusively expressed in primary sensory neurons and are suggested to play a role in different pain conditions, including chronic inflammatory and neuropathic pain states. Since no selective pharmacological tools are available, we investigated the involvement of Na(v)1.8 and Na(v)1.9 in pain transmission by the phenotypic characterization of Na(v)1.8 and Na(v)1.9 knockout mice and their wild-type littermates in models of acute nociception, peripheral inflammation and neuropathic pain. The present study provides evidence for a modulatory role of Na(v)1.9, and to a lesser extent Na(v)1.8 in the development of cold, but not mechanical allodynia in neuropathic pain conditions. Moreover, our results also indicate that Na(v)1.9 signaling might be involved in visceral pain. In contrast, the presumed critical role of these two sodium channel subtypes to inflammatory pain hypersensitivity seem, according to our results, to be limited and temporarily.
Leo
Sandra
S
Johnson & Johnson Pharmaceutical Research and Development, Janssen Pharmaceutica, Turnhoutseweg 30, B- 2340 Beerse, Belgium. sandra.leo@psy.kuleuven.be
D'Hooge
Rudi
R
Meert
Theo
T
D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides / Q000172:deficiency*; D009619:Nociceptors / Q000502:physiology*; D010146:Pain / Q000145:classification / Q000209:etiology* / Q000235:genetics*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D010812:Physical Stimulation / Q000009:adverse effects; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D015222:Sodium Channels / Q000172:deficiency*
D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C568318:Scn10a protein, mouse; C491885:Scn11a protein, mouse; D015222:Sodium Channels