Trinitrobenzenesulphonic acid colitis alters Nav 1.8 channel expression in mouse dorsal root ganglia neurons

Visceral inflammation evokes hyperexcitability in nociceptive dorsal root ganglia (DRG) neurons and these changes are associated with increased voltage‐gated sodium channel (Nav) 1.8 current density, but the molecular determinants of these changes are unclear. This study used Western blotting to measure changes in Nav 1.7, 1.8 and 1.9 protein expression during trinitrobenzenesulphonic acid (TNBS) colitis and quantitative polymerase chain reaction (PCR) to examine corresponding changes in mRNA. Colonic neurons were labelled with the retrograde tracer Fast Blue injected into the wall of the distal colon and quantitative PCR performed on laser‐captured labelled colonic neurons from ganglia at T9‐13 or unlabelled DRG neurons from the upper spinal cord. Immunohistochemistry and western blots were performed on whole DRG from the same sites. Fast Blue‐labelled neurons demonstrated Nav 1.7, 1.8 and 1.9 immunoreactivity. On day 7 of colitis, which correlated with electrophysiological studies, there was a threefold increase in Nav 1.8 protein in ganglia from T9 to 13, but Nav 1.7 and 1.9 levels were unchanged. There was no corresponding change in the Nav 1.8 α‐subunit mRNA levels. However, on days 2 and 4, Nav 1.8 mRNA was decreased 10‐fold. Nav 1.8 protein and mRNA levels were unchanged in neurons isolated from ganglia in the upper spinal cord, where colonic neurons are not found. These findings suggest that the TNBS evoked increase in Nav 1.8 currents is associated with increased numbers of channels. The absence of corresponding changes in transcript suggests a translational or post‐translational mechanism, but the 10‐fold recovery of transcript preceding this time point also demonstrates a complex transcriptional regulation.