Activation Of Group â…¢ Metabotropic Glutamate Receptors Inhibits Formalin-induced Activation Of Spinal P38-MAPK In Rats

Objective:It is generally accepted that central nociception is based on the initiation of centripetal signals from peripheral nociceptors by peripheral nociceptors are transmitted into the spinal dorsal horn.Evidence from the last decades indicates that glutamate plays a significant role in nociceptive processing by activation of both iGluRs and mGluRs.In previous study,we showed that activation of mGluRsⅢcan strengthen both processes of generation of nociceptive signals in peripheral nociceptors and transmission of nociceptive information in spinal dorsal horn by observating of nociceptive behavior combined with Fos expression examinations produced by peripherally injection Formalin.The aim of the present study is to further confirmed GroupⅢmGluRs are involved in the processing of noxious signals in peripheral nociceptors and nociceptive transmission in spinal cord by using the same model,by observating of nociceptive behavior combined with p38MAPK activated examinations produced by peripherally injection Formalin.Methods:There were two parts of experiments.The first part of the experiment was designed for the examination of peripheral processing of noxious signals and fourty-eight male Wistar rats were divided randomly into four groups:control group or NS group and three different dose of L-SOP groups(100nmol,250nmol,500nmol).L-SOP group was experimental group with injection of selective GroupⅢmGluRs agonist L-SOP into the plantar aspect of the left hindpaw;and NS group was controlled with injection of normal saline.In all the four group,Formalin was injected 20 min after the pretreatment of agonist L-SOP or NS at the same site.For each group,6 rats used to observe flinching and licking time every as nociception behavior 3 minutes in 1 hour after formalin injected and the other 6 rots used to observe the activation of p38(P-p38) by western-blot.The second part of the experiment was carried out for the observations of spinal mechanisms of nociceptive processing.Fourty-eight male Wistar rats were divided randomly into four groups:control group or NS group and three different dose of L-SOP groups(100nmol,250nmol,500nmol).L-SOP group was experimental group with intrathecal injection of L-SOP;and NS group was controlled with intrathecal injection of normal saline.In all the four group,Formalin was injected at the site of the plantar aspect of the left hindpaw in the four group 20 min after the pretreatment of agonist L-SOP or NS.For each group,6 rats used to observe flinching and licking time every as nociception behavior 3 minutes in 1 hour after formalin injected and the other 6 rats used to observe the activation of p38 (P-p38) by western-blot.Results:1.In the examination of peripheral processing of noxious signal,all the three different groups of L-SOP can inhibit noeiception behavior in the Tonic phase,and 250nmol and 500nmol groups can suppress not only in the tonic phase but also in the acute phase.250nmol and 500nmol groups can reduce activated or phosphorylated p38MAPK in spinal cord(P＜0.05). 2.In the examination of spinal mechanisms of noeiceptive processing,all the three different groups of L-SOP can inhibit nociception behavior in the Tonic phase but with no effects on the acute phase.All the three different groups of L-SOP can reduce activated or phosphorylated p38MAPK in spinal cord(P＜0.05).Conclusion Periphery or intrathecal injection of L-SOP can reduce noeiceptive behavior and phosphorylated p38MAPK in the spinal cord in formalin-induced hyperalgia,it is suggested that there are functional expression of mGluRsⅢin the periphery and spinal and there are involved in the processing of peripheral noxious informations.