Lack of colonic inflammation‐induced acute visceral hypersensitivity to colorectal distension in Na v 1.9 knockout mice

Tetrodotoxin‐resistant voltage‐gated sodium channels subtype 9 (Na v 1.9) are expressed in small‐diameter dorsal root ganglion neurons and have been involved in persistent somatic hyperalgesic responses associated with inflammation. We assessed the role of Na v 1.9 channels on acute colonic inflammation‐induced visceral hypersensitivity in conscious mice, using Na v 1.9 knockout (KO) mice. Colorectal distension (CRD)‐induced visceral pain was assessed in conscious wild‐type and Na v 1.9 KO mice (C57Bl/6 background). The mechanical activity of the abdominal muscles during isobaric colorectal distension was used as a measure of visceral pain. Acute colonic inflammation was induced by intracolonic administration of the toll‐like receptor (TLR) 7 activator, R‐848 (40μg/animal). CRD was performed 5h later, thereafter animals were euthanized and the colonic content of inflammatory mediators assessed. Normal pain responses were similar in Na v 1.9 KO and wild‐type mice. In wild‐type mice, R‐848 administration increased the response to phasic CRD by 62% compared with vehicle‐treated animals (vehicle: 0.16±0.04, R‐848: 0.26±0.03, n =6–7, P <0.05). However, in Na v 1.9 KO mice, intracolonic R‐848 did not affect the response to CRD (0.11±0.02, n =7) compared to animals treated with vehicle (0.17±0.03, n =5; P >0.05). After R‐848 administration, the colonic content of pro‐inflammatory cytokines was increased in similar proportion in wild type and Na v 1.9 KO mice, suggesting the presence of a similar acute inflammatory reaction in both groups of animals. These results suggest that Na v 1.9 channels do not significantly contribute to normal visceral pain responses to acute colonic mechanical stimulation but may be important for the development of inflammation‐related acute visceral hyperalgesic responses.