Modulation Effect Of Mas-related Gene Receptors On Neuropathic Pain And The Role Of Adrenomedulline In Pain

Mas-related gene receptors (Mrg receptors) is uniquely located in trigeminal ganglia (TG) and the small diameter neurons dorsal root ganglia (DRG). It has been demonstrated that intermittent administration of bovine adrenal medulla8-22(BAM8-22), a selective Mrg receptors agonist, can inhibit the sciatic nerve ligation-induced hyperalgesia. Studies have shown that glial cells, Fractalkine, IL-1β and adrenomedullin are involved in the formation and maintenance of pain.This study was presented by testing the rats’ mechanical threshold and Immuno histochemical techniques to examine:(1) Effects of intrathecal injection BAM8-22on the mechanical hyperalgesia induced by ligation L5spinal nerve and SNL-induced change of astrocytes in the spinal dorsal horn of rat.(2) Effects of intrathecal injection BAM8-22on the SNL-induced change of fractalkine, IL-1β in DRG.(3) Effects of intrathecal injection AM and H89on the thermal hyperalgesia. Results showed that:(1) the paw withdraw pressure threshold dropped to about50%of the baseline latency on10th day after spinal nerve ligation (2) The expression of GFAP in the spinal dorsal horn and fractalkine, IL-1β in dorsal root ganglion were increased following the surgery of SNL. Applying BAM8-22to activate the Mrg receptors can inhibit the increase of GFAP, fractalkine and IL-1β, so as to reduce the hyperalgesia of the spinal nerve ligation rats.(3) Applying AM can reduce the tail-flick latency. However, co-administration of AM with H89everyday will keep the tail-flick latency steadily.This study indicates that the activation of Mrg receptors may be involved in inhibiting the maintenance of neuropathic pain. It is possible that inhibit the expression of GFAP, Fractalkine and IL-1β can relieve SNL-induced hyperalgesia in pain. AM can participate in the regulation of pain, and its mechanism may be transmit pain signals through the activation of cAMP/PKA pathway.