Effect Of NK-1 Receptor On P38MAPK Activasion In Spinal Cord Of The Formalin Test Rats

Objective:To assess the effect of NK-1 receptor on rat's behavior response and p38MAPK activasion in spinal cord.Methods:The experiment is divided into two parts.The first part is the peripheral test.Investigation of rat's behavior:24 male Wister rats were randomly divided into 4 groups(n=6 each).Including control group(DMSO) and three different dose of RP67580 groups:5nmol;20nmol;100nmol.All groups were injected medicine(or dissolvent) into the dorsal surface of the left hind paw,after 15 min,injected 5%formalin 50ul into the same site,then observed the behavior and calculated the time of licking or biting injected paw every 3 min for 1 hour.Western blot test:The groups were as the same as the test before,the spinal p38 MAPK identified by the Western Blot technique after the injection of formalin 20 min.The second part is the center test:Investigation of rat's behavior:24 male Wister rats which operated successfully were randomly divided into 4 groups(n=6 each).Including control group(DMSO) and three different dose of RP67580 groups:5nmol;20nmol;100nmol.All groups were injected medicine(or dissolvent) intrathecally,after 15 min,injected 5%formalin 50ul into the same site,then observed the behavior and calculated the time of licking or biting injected paw every 3 min for 1 hour.Western blot test:The groups were as the same as the test before,the spinal p38 MAPK identified by the Western Blot technique after the injection of formalin 20 min.Result1.Effect of peripheral NK-1 receptor on p38MAPK activation in spinal cord of the formalin test ratsInvestigation of rat's behavior:The group of 5nmol and 20nmol had no effect on the pain reaction in phaseⅠbut had effect in phaseⅡ,the time of licking or biting was shorter than the control group;The group of 100nmol had effect on it in phaseⅠandⅡ,the time of licking or biting was shorter than the control group(p＜0.05).Western blot test:Compared with the control group,the expression of phosphorylated p38MAPK(P-p38) in spinal cord in all experiment groups were decreased(P＜0.01). 2.Effect of spinal NK-1 receptor on p38MAPK activation in spinal cord of the formalin test ratsInvestigation of rat's behavior:The group of 5nmol had no effect on the pain reaction in phaseⅠbut had effect in phaseⅡ,the time of licking or biting was shorter than the control group;The group of 20nmol and 100nmol had effect on it in phaseⅠandⅡ,the time of licking or biting was shorter than the control group(p＜0.05).Western blot test:Compared with the control group,the expression of phosphorylated p38MAPK(P-p38) in spinal cord in all experiment groups were decreased(P＜0.01),and the difference between experiment groups was significant(P＜0.05).The expression of P-p38 was decreased significantly with the increase of medicine dosage.Conclusions:1.Peripheral or intrathecal administration of NK-1 receptor antagonist RP67580 could inhibit the rat's pain response induced by injection of formalin.2.Peripheral or intrathecal administration of NK-1 receptor antagonist RP67580 could inhibit the activation of p38MAPK in spinal cord induced by injection of formalin.3.The effect of NK-1 receptor on the rat's pain response at least partly mediated by the p38MAPK pathway.