OBJECTIVE To explore the relationship between hyperpolarization-activated cyclic nucleotidegated channels (HCN) and the comorbid neuropathic pain and mental disorder.METHODS Rat spared nerve injury (SNI) model was setup and ZD7288, an antagonist of HCN channel, was administrated by intracerebroventricular injection.The touch threshold and paw withdrawallatency of SNI rats were measured.The open field, elevated plus maze and forced swimming test were performed.The expression level of HCN channel was tested.RESULTS After SNI surgery, the pain threshold and paw withdrawal latency decreased.The expression level of HCN was increased in hippocampus and thalamus.ZD7288 (5 μg· kg-1) could increase the touch threshold significantly and partial ameliorate anxiety as well as depression like behavior.CONCLUSION ZD7288 plays an analgesic effect and ameliorate anxiety as well as depression like behaviors in SNI rats by blocking HCN channels.HCN channel is possibly involve in the comorbid neuropathic pain and mental disorder.