Spinal cord plasticity and acid-sensing ion channels involvement in a rodent model of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common functional gastro-intestinal disorder characterized by intractable chronic abdominal pain. In this study, we examined the possible spinal mechanisms underlying colonic hypersensitivity (CHS) using a non-inflammatory rat model of IBS induced by rectal enemas of butyrate, a short-chain fatty acid. We hypothesized that spinal plasticity could be responsible for CHS and that ASIC channels, which are known to support pain-elicited currents in the spinal cord, could contribute to central sensitization in our model of IBS. First, in order to determine if visceral pain relies on changes in spinal activity, we analyzed Fos expression in the spinal cord of rats treated with butyrate following a challenge with repetitive noxious colorectal distension. We found that Fos immunoreactivity was increased in thoracic T10-11-12, lumbar L1-2-6 and sacral S1 spinal segments. In control rats treated with saline, noxious repetitive colorectal distensions evoked Fos expression only in L1-2-6 and S1 spinal segments. Secondly, intrathecal injection of PcTx1, a specific ASIC1A antagonist, in the lumbar spinal cord completely prevented the development of CHS induced by butyrate. ASIC1 and 2 mRNAs, especially ASIC1A, were upregulated in the lumbar spinal cord. ASIC1A could thus contribute to spinal sensitization in our model of IBS, as it is supported by spinal colocalization of ASIC1A and Fos proteins. The whole data pinpoint a potential critical role of thoracic spinal cord in non-inflammatory pain states such as IBS and suggest that ASIC channels are part of the molecular effectors of central sensitization leading to visceral pain.