The Contribution Of Peripheral 5-hydroxytryptamine 2A Receptors To Carrageenan-evoked Inflammatory Pain And Its Mechanisms

Nitro oxide(NO)and protein kinase C(PKC)are important intracellular messenger molecules and involved in the pathological process of inflammatory pain.The present study was designed to investigate the cellular mechanisms of peripheral 5-HT_2Areceptors in the matainence of carrageenan-evoked hyperalgesia.This study was conducted by using behavioral,immunohistochemical,histochemistry and Western blot techniques to investigate the effects of blockade of 5-HT_2Areceptors on hyperalgesia induced by intraplantar(i.pl)injection of carrageenan.We found that post-treatment with i.pl injection of ketanserin,a selective antagonist of 5-HT_2Areceptor,in the hindpaw produced hypoalgesia in the late phase of carrageenan-evoked inflammation and inhibited the expression of nitric oxide synthase(NOS)in the spinal dorsal horn.Consistentlly,exogenous administration of 5-HT increased the expression of NOS.Furthermore,ketanserin inhibited the formalin-induced pain response and expression of NOS and PKCv in the spinal dorsal horn at segments L4-5.Subcutaneous administration naloxone methiodide,an nonselective opioid receptors antagonist which doesn't across the blood-brain barrier(BBB),reversed the hyporalgesia and the expression of Fos and NOS in the spinal dorsal horn. The present study provided evidence supporting that periphe.ral 5-HT plays an role in the matainence of inflammatory hyperalgesia via activation of peripheral 5-HT2A receptor.It is propose,d that endogenous opioids may mediate the effects of blockade of 5-HT2A receptors and NO or PKC signal pathways are involved in inflammatory hyperalgesia.