| Objective: To investigate the effect of intermedin (IMD) and its receptor of dorsalroot ganglia on chronic neuropathic pain of chronic constriction injury (CCI) rats.Method: The CCI rats were used as the neuropathic pain model. Adult maleSprague-Dawley rats were randomly assigned to five goups for varied purpose: blankcontrol group (Control), sham operation group (Sham), CCI rats treated with normalsaline group (CCI+NS),CCI rats treated with IMD1-53group(CCI+IMD1-53), CCI ratstreaed with IMD inhabitor IMD14-47group(CCI+IMD14-47). Mechanical withdrawalthreshold(MWT) was tested by von Frey, and thermal withdrawal latency(TWL) wastested by automatic thermal stimulus instrument.The change of expression of P2X3receptor, IMD and its receptor of rat L4/L5DRG were detected with immunoflurescence,RT-PCR, Western Blotting, immunohistochemistry, co-immunoprecipitation, and thephosphorylation of P38and ERK1/2was detected by Western Blotting.Result: On day14after CCI surgery, MWT and TWL in the surgery side limbs ofCCI+NS and CCI+IMD1-53and CCI+IMD14-47were lower than those in Control andSham group (p<0.01), indicating that we made the CCI model successfully.7days afterthe intrathecal catheter, CCI+NS and CCI+IMD1-53still maintained obvious mechanicaland thermal hyperalgesia, but CCI+IMD14-47had an obvious increase of MWT and TWL,which indicated a relief of mechanical and thermal hyperalgesia. Meanwhile the results ofimmunoflurescence, RT-PCR, Western Blotting, immunohistochemistry showed that therewas a significant increase of the expression of P2X3receptor, IMD and its receptor inL4/L5DRG in CCI+NS and CCI+IMD1-53compared with those in Control and Shamgroup(P<0.05), and much obvious in CCI+IMD1-53. After application of IMD inhibitorIMD14-47, in group CCI+IMD14-47,there were a decrease in expression of P2X3receptor,IMD and its receptor of L4/L5DRG(P<0.05). The result of immunoflurescence showedthat P2X3receptor and IMD co-expressed in the neuron of DRG. And the result ofco-immunoprecipitation indicated that P2X3receptor interacted with IMD. Furthermore,the results of Western Blotting showed that the phosphorylation of p38and ERK1/2inCCI+NS group was stronger than that in Control and Sham group (p<0.05), however, the phosphorylation of p38and ERK in CCI+IMD14-47group was much lower than that inCCI+NS group(p<0.05)Conclusion: IMD and its receptor may play a key role in the pain transmission ofneuropathic pain mediated by P2X3receptor in CCI rats, and IMD inhibitor IMD14-47could have inhibitory effects on neuropathic pain by suppressing the expression andactivation of P2X3receptor of DRG. |
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