Study On The Role Of Transient Receptor Potential Channel 8 With The Involvement Of Nuclear Factor Kappa B In Modulation Of Neuropathic Pain In Rats

Objective: To observe the effects of intrathecal injection of NF-?B inhibitor PDTC on the pain behavior and expression of TRPM8 and NF-?B p65 in dorsal root ganglion in rats with chronic constrictive injury(CCI).To explore the mechanism and the role oftransient receptor potential channel 8 with the involvement of nuclear factor kappa B in modulation of neuropathic pain in rats.Methods: Thirty-six special pathogen-free healthy adult male Sprague-Dawley rats with successful intrathecalcatheter implantation,weighing 180-200 g,aged 4-6 weeks old,were divided into 3 groups(n=12 each)by using a random number table,respectively,sham operation group(group S),neuropathic pain group(group NP)and NF-?B bocker PDTC group(group PDTC).The third day after intrathecal catheter was successfully implanted,neuropathic pain model was made from group NP and group PDTC based on chronic constriction injury(CCI),Group S was only isolated the trunk of sciatic nerve without ligation.PDTC 10?l(Concentration of 2mg/ml,dissolved with saline)was intrathecally injected twice a day fro m the 1st postoperative day and the injection lasted for the next 13 days.After the injection,10?l physiological saline was used to rinse.Group S and group NP were intrathecally injec ted equal 20?l of physiological saline and 30 minutes after intrathecal administration,the cold pain,thermal,and mechanical thresholds were measured on preoperative day 1 and postoperative days 1,3,7,10 and 14.The rats were dispatched and the dorsal root ganglions were removed on postoperative days 7 and 14 for determination of the expression of TRPM8 and NF-?B p65 using Western blot.Results: Compared with group S,The cold pain,thermal,and mechanical thresholds were significantly decreased on the postoperative 1 day?3 day?7 day?10 day?14 day in group NP(P<0.05).Compared with group S,the expression of TRPM8 and NF-?B p65 in dorsal root ganglions was significantly increased on postoperative days 7 and 14 in group NP(P<0.05).Compared with group NP,the cold pain,thermal,and mechanical thresholds were significantly on postoperative 3 day?7 day?10 day?14 day increased in group PDTC(P<0.05).Compared with group NP,the expression of TRPM8 and NF-?B p65 in dorsal root ganglions was significantly decreased on postoperative days 7 and 14 in group PDTC(P<0.05).Conclusion: The up-regulation of expression of TRPM8 and NF-?B in dorsal root ganglions correlates with the neuropathic pain and inhibiting the activation of NF-?B can relieve the up-regulation of the expression of TRPM8 as well as the hyperalgesia of rats.