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Objective Previous work done has shown that colorectal distensions (CRD) in neonates can engender chronic visceral hypersensitivity in adult rats.Earlier studies have shown that acute visceral hyperalgesia produced by colon inflammation is attenuated by hyperpolarization-activated cyclic nucleotide gated cation (HCN) channel blocker-ZD7288.The present study is to assess the contribution of spinal HCN 1 and HCN2 to chronic visceral hypersensitivity.Methods Experiments were done on 48 male adult Sprague-Dawley rats: 24 neonates received CRD as models and the others served as controls.Model rats received 60 mmHg CRD once daily on post neonatal days 8-14.Abdominal withdrawal reflex and spikes of external oblique muscle of abdomen were tested to assess the visceral sensitivity of rats.ZD7288 at the dose of 25-100 nM was given to the control and model rats by intrathecal application; The expression and distribution of HCN1 and HCN2 channel protein in thoracolumbar and lunbosacral spinal cord were detected by immunohistochemical techniques in control and model rats.Results (1)The reaction to pain in rats with chronic visceral pain can be inhibited and the pain threshold can be increased by intrathecal application of ZD7288 in a dose-dependent manner.(2) The expression of HCNland HCN2 channel protein are significantly increased on thoracolumbar and lunbosacral spinal cord in chronic model rats than in control rats.Conclusion In summary, the results indicate that spinal HCN1 and HCN2 subunits could be involved in central mechanism of chronic visceral sensitization in model rats.