“疼痛感受性”施万细胞中TRPV4通道在机械痛感知中的作用和调控机制的研究

目前临床上缺乏针对病理性疼痛的有效治疗手段，主要原因在于疼痛的发生和传递机制仍不明确。近期有文章发现，有一类非成髓施万细胞包裹在痛觉神经末梢周围，可最先感受伤害性机械刺激从而引发疼痛，而此过程中施万细胞对机械性刺激的感受机制和痛觉信息传递机制都尚不知晓。前期研究中，我们已明确机械敏感性通道TRPV4通道在非成髓施万细胞中功能性表达，且在神经损伤后TRPV4通道的表达量和活性都显著增加。本课题拟结合免疫荧光三维成像技术和膜片钳技术，详细解析“疼痛感受性”施万细胞中TRPV4通道在机械性疼痛感受中的作用。并进一步利用扫描电镜技术、转录组学、免疫学技术和膜片钳技术，深入研究痛觉信息由“疼痛感受性”施万细胞传递给初级神经的分子机制。在此基础上，我们拟初步探索TRPV4是否参与由外周敏化引起的神经病理性疼痛，为治疗由外周敏化引起的神经病理性疼痛提供新的切入点，为临床疼痛治疗药物研发提供新思路。

In current clinical treatment, effectiveness of pain management for patients with pathological pain is limited, mainly because the mechanisms of pain initiation and transmission are unclear. A recent report found that there is a type of non-myelinating Schwann cells that surround the nociceptive sensory nerve endings are capable of detect the noxious mechanical stimuli at the first time and initiate pain sensation. However, the mechanisms underlying the detection and transmission of noxious mechanical stimulus in Schwann cells are still unknown. In preliminary studies, we have confirmed that TRPV4 channel is the functionally expressed in non-myelinating Schwann cells, and the expression and activation of TRPV4 channel are both significantly increased in response to nerve injury. In this project, we intend to identify the functions of TRPV4 channel of Schwann cells in detection of noxious mechanical stimulus in details by synthetical application of three-dimensional immunofluorescence imaging and patch clamp recording. In addition, by using the method of scanning electron microscopy, RNA sequencing, immunostaining and patch clamp recording, we intend to further study the molecular mechanisms of nociceptive signal transmission from nociceptive Schwann cells to sensory neurons. Based on this, we would try to find whether TRPV4 in Schwann cells is involved in peripheral sensitization-mediated neuropathic pain sensation. Our results could provide a new view for the treatment of neuropathic pain caused by peripheral sensitization, and could provide new ideas for developing anti-analgesic drugs in pain therapies.