Abstract
Nicotinic acetylcholine receptors can regulate inflammation primarily through the vagus nerve via the cholinergic anti-inflammatory pathway. alpha 9 alpha 10 nicotinic receptors (nAChRs) are a new promising target for chronic pain and inflammation. Recently, alpha 9 alpha 10 selective alpha-conotoxin antagonists were shown to have antinociception effect in neuropathic and tonic inflammatory pain animal models. However, limited data available on the role of alpha 9 alpha 10 nAChRs in experimental colitis. In this study, we report for the first time, the role of alpha 9 alpha 10 nAChRs in the dextran sodium sulfate (DSS) experimental animal colitis model. We determined the effect of the alpha 9 alpha 10 nAChRs antagonist, alpha-conotoxin RgIA (alpha-RgIA) in DSS-induced colitis model in adult male and female C57BL/6 J mice. DSS solution was freely given in the drinking water for seven consecutive days, and tap water was given on the 8th day. We then sacrificed mice on day 8 to examine the entire colon. Disease severity, colon tissue histology, and tumor necrosis factor-alpha (TNF-alpha) were evaluated. The lower doses (0.02 and 0.1 nmol/mouse, s.c.) of alpha-RgIA treatment in DSS-treated mice were inactive, whereas the higher dose (0.2 nmol/mouse, s.c.) reversed the disease activity index (DAI) score, loss of body weight, total histological damage score, as well as the colonic level of TNF-alpha compared to the DSS-control group. Moreover, the highest dose of alpha-RgIA (0.2 nmol/mouse, s.c.) significantly rescued the colon length shortening in DSS-treated mice compared to the DSS-control mice. The availability of alpha 9*-selective conotoxins has opened new avenues in pharmacology research and potential targets in inflammatory disorders.