Group Ⅲ Metabotropic Glutamate Receptors Are Involved In The Activation Of Peripheral Nociceptors And The Modulation Of Spinal Nociceptive Signals

It is generally accepted that central nociception is based on the initiation of centripetal signals from peripheral nociceptors activated by peripheral noxious stimulation. Nociceptive inputs produced by peripheral nociceptors are transmitted into the spinal dorsal horn and also modulated by multiple substrates in 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 Groupâ… mGluRs can strengthen both processes of generation of nociceptive signals in peripheral nociceptors and transmission of nociceptive information in spinal dorsal horn by using Formalin test. The aim of the present study is to investigate if Group â…¢ mGluRs are involved in the processing of noxious signals in peripheral nociceptors and nociceptive transmission in spinal cord as Groupâ… mGluRs do by using the same model, e.g. observation of nociceptive behavior combined with Fos expression examinations produced by peripherally injection Formalin. There were two parts of experiments. The first part of the experiment was designed for the examination of peripheral processing of noxious signals and animals were divided into auto-control and iso-control groups. In the iso-control group animals were further divided into two groups (n=5): one of them was experimental group with injection of selective Group â…¢ mGluRs agonist L-SOP into the plantar aspect of the left hindpaw; and the other group was controlled with injection of normal saline(NS). In both groups, Formalin was injected 15 min after the pretreatment of agonist L-SOP or NS at the same site, and then carried out behavioral observation by examining the total time for licking and biting towards the injected hindpaw by rats, and then examined Fos expression in spinal dorsal horn one hour late after Formalin injection. In the auto-control group, Formalin was injected in both hindpaws and one of them was administered with L-SOP. In this case, only Fos expression in both sides of the spinal cord were examined by immunohistochemical procedures. The second part of the experiment was carried out for the observations of spinal mechanisms of nociceptive processing. Animals were divided into two groups (n=5): one of them was experimental group with intrathecal injection of L-SOP; and the other was controled with intrathecal injection of NS. Formalin was injected at the site of the plantar aspect of the left hindpaw in the two groups 15 min after the pretreatment of L-SOP or NS. The behavioral observation of nociceptive responses were carried out immediately after Formalin administration, and one hour later after Formalin injection, rats were killed for immunohistochemical procedures for Fos expression in the dorsal horn. Behavioral observation in control group showed that injection of Formalin into one plantar aspect of hindpaw resulted in biphasic behavioral responses of licking and biting towards the injected paw named first or acute phase and second or tonic phase. Whether peripheral or intrathecal administration of L-SOP produced significant suppression in the tonic phase of nociceptive responses with no effects on the acute phase responses. In the immunohistochemical examination of Fos expression, subcutaneous injection of Formalin induced significant increase of Fos-like immunoreactive (FLI) neurons which could be found mainly in the dorsal horn ipsilateral to the injection of Formalin, while combined pretreatment of L-SOP significantly suppressed the Fos expression in spinal dorsal horn in the drug-injected group or in ipsilateral side of drug pretreated in both parts of experiments.These results indicated that: Group â…¢ mGluRs may be expressed in terminals of peripheral primary afferent fibers and involved in the peripheral processing of noxious signals; they are also involved in the modulation of nociceptive information in spinal cord; activation Group â…¢ mGluRs in turn suppress both the generation of noxious signals in perip...