Thalamic neural activation in the cyclophosphamide-induced visceral pain model in mice

The afferent nociceptive information from the lower urinary tract terminates in the dorsal horn of the spinal cord, and then projects to the thalamus. In the present study, we examined the effects of visceral nociception from the lower urinary tract on the neural activity of thalamic neurons using cyclophosphamide (CP)-induced cystitis, a model of visceral nociception. The levels of c-fos mRNA as well as protein, a marker of neural activation, were investigated in the thalamus using in situ hybridization histochemistry and immunohistochemistry. The effects of pretreatment with capsaicin were also examined. In the CP-treated group, the c-fos mRNA as well as protein was significantly induced predominantly in the paraventricular area of the thalamus. The induction of c-fos mRNA exhibited a dose-dependency. The induction of c-fos mRNA of CP-treated mice was significantly inhibited by capsaicin pretreatment to deplete C-fibers. Our results indicate that visceral nociception from the lower urinary tract activates thalamic neurons and this activation is mediated in part through the activation of the capsaicin-sensitive C-fiber afferents. The present findings suggest that the levels of c-fos in the paraventricular area of the thalamus may be a useful marker for evaluating the afferent nerve activity from the lower urinary tract.