The Role Of Peripheral 5-HT_2A Receptors In Neuropathic Pain

Neuropathic pain is a major challenge that has been the distress of patients and doctors in the world. Previousely studies have confirmed that 5-HT2A receptors in peripheral are pay an important role in acute inflammatory pain. Our lab study had found that peripheral 5-HT2A receptors are also responsible for musculeskeletal involved-pain syndrome that caused by chronic inflammation and neuropathic pain. However, the mechanism of action of 5-HT2Areceptor in neuropathic pain is still unclear. Through the establishment of L5 spinal nerve ligation model, we investigate the role of neuropathic pain in peripheral 5-HT2A receptor. And moreover we find out the possible mechanism on how ketanserin alleviate neuropathic pain after the administation of 5-HT2A receptor antagonist (ketanserin) to cervical part of rat subcutaneous.The behavior results showed that blocking peripheral 5-HT2A receptors can significantly alleviate the neuropathic pain induced by thermal hyperalgesia and mechanical hyperalgesia. From the cellular level, further research found that large quantities of neuropeptide Y was expression in large and medium-sized cells in dorsal root ganglia after the spinal nerve ligation, however in normal state, NPY never or little express in DRG cells; NPY and calcitonin gene-related protein (CGRP) was also increased significantly in spinal dorsal horn. But the expression levels of NPY and calcitonin gene-related protein (CGRP) significanes discrease after the administation of 5-HT2A receptor antagonist (ketanserin) in cervical part of rat subcutaneous. These results indicate that peripheral 5-HT2A receptors is involved in neuropathic pain and its mecanism is relatve to the release of NPY and CGRP. And the synthesis of NPY and CGRP.Our research demostrate:blocking the peripheral 5-HT2A receptor can significantly reduce hyperalgesia caused by the L5 spinal nerve ligation. This stamement will providing a new theory that could be use in the therapy for the clinical disorders.