Involvement of Brn3a-positive spinal dorsal horn neurons in the transmission of visceral pain in inflammatory bowel disease model mice

Spinal dorsal horn plays crucial roles in the transmission and processing of somatosensory information. Although spinal neural circuits which process several distinct types of cutaneous sensation have been extensively studied, those responsible for visceral pain transmission remain poorly understood. In the present study, we analyzed the dextran sodium sulfate (DSS)-induced inflammatory bowel disease (IBD) model mice to characterize the spinal dorsal horn neurons involved in visceral pain transmission. DSS-treated mice exhibited increased abdominal licking behavior, suggestive of experiencing visceral pain. Immunostaining of c-fos, a marker indicating neuronal activity, demonstrated that numerous c-fos-positive cells were found bilaterally in the lumbosacral spinal dorsal horn, and their distribution was particularly abundant in the shallow dorsal horn. Neurochemical characterization of these neurons revealed that the percentage of the POU transcription factor Brn3a-positive neurons among the c-fos-positive neurons in the shallow dorsal horn was 30-40% in DSS-treated mice, which was significantly higher than that in the somatic pain model mice. We further demonstrated by neuronal tracing that within the shallow dorsal horn, Brn3a-positive neurons are represented more highly in spino-solitary projection neurons than in spino-parabrachial projection ones. These results raised the possibility that Brn3a-positive spinal dorsal horn neurons make a large contribution to visceral pain transmission, and part of which was mediated through spino-solitary pathway.