Introduction: Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide(CGRP) family.Preprointermedin can be cleavaged between Arg93 and Arg94, resulting in the productionof prepro-IMD95-147, namely IMD1-53.A fragment of IMD, IMD17-47, has been described as a functional antagonist of the peptide.This study aimed to investigate the effect of IMD and its receptors on neuropathic pain.Methods:Chronic constriction injury (CCI) rat model was used in this study.Sprague-Dawley rat were randomly divided into four groups: sham + saline group, CCI + saline group, CCI+ IMD1-53 group and CCI+ IMD17-47 group.Mechanical withdrawal threshold and thermal withdrawal latency were measured after operation for two weeks.On the day 14 after operation, the expression of the IMD and its receptors in dorsal root ganglion (DRG) of rats was detected by immunohistochemistry, Western-blotting and RT-PCR.At the same time the expression of P2X3 receptors in DRG of those rats was detected too.Results: The results showed mechanical withdrawal threshold and thermal withdrawal latency in CCI + saline group were lower than those in sham + saline group and CCI +IMD17-47 group (P<0.05), but was higher than those in CCI+ IMD1-53 group (P<0.05).And the expression of P2X3receptor, IMD and its receptor in DRG of CCI+ saline group and CCI+ IMD1-53 group are obviously higher than those in other two groups (P<0.05).After treatment of IMD17-47 in CCI rats, the expression of P2X3 receptor, IMD and its receptor was significantly decreased compared with that in CCI+ IMD1-53 group (P<0.05).Conclusion: In summary, IMD may facilitate the pain transmission of CCI rat, and its effect may involve the expression of P2X3receptors in DRG.