PDF(Pubmed)
Abstract：
Despite the unique and complex nature of cancer pain, the activation of different ion channels can be related to the initiation and maintenance of pain. The transient receptor potential vanilloid 4 (TRPV4) is a cation channel broadly expressed in sensory afferent neurons. This channel is activated by multiple stimuli to mediate pain perception associated with inflammatory and neuropathic pain. Here, we focused on summarizing the role of TRPV4 in cancer etiology and cancer-induced pain mechanisms. Many studies revealed that the administration of a TRPV4 antagonist and TRPV4 knockdown diminishes nociception in chemotherapy-induced peripheral neuropathy (CIPN). Although the evidence on TRPV4 channels\' involvement in cancer pain is scarce, the expression of these receptors was reportedly enhanced in cancer-induced bone pain (CIBP), perineural, and orofacial cancer models following the inoculation of tumor cells to the bone marrow cavity, sciatic nerve, and tongue, respectively. Effective pain management is a continuous problem for patients diagnosed with cancer, and current guidelines fail to address a mechanism-based treatment. Therefore, examining new molecules with potential antinociceptive properties targeting TRPV4 modulation would be interesting. Identifying such agents could lead to the development of treatment strategies with improved pain-relieving effects and fewer adverse effects than the currently available analgesics.
摘要：
尽管癌症疼痛具有独特而复杂的性质，不同离子通道的激活可能与疼痛的启动和维持有关。瞬时受体电位香草酸4（TRPV4）是在感觉传入神经元中广泛表达的阳离子通道。该通道被多种刺激激活以介导与炎性和神经性疼痛相关的疼痛感知。这里,我们重点总结了TRPV4在癌症病因和癌症诱发疼痛机制中的作用.许多研究表明，在化疗诱导的周围神经病变（CIPN）中，使用TRPV4拮抗剂和TRPV4敲低可减少伤害感受。虽然TRPV4通道参与癌痛的证据很少，据报道，这些受体的表达在癌症诱导的骨痛（CIBP）中增强，神经周,和将肿瘤细胞接种到骨髓腔后的口面癌症模型，坐骨神经,还有舌头,分别。有效的疼痛管理对于被诊断患有癌症的患者来说是一个持续的问题，目前的指南未能解决基于机制的治疗。因此,研究靶向TRPV4调节的具有潜在抗伤害感受特性的新分子将是有趣的。与目前可用的镇痛药相比，鉴定此类药物可导致开发具有改善的疼痛缓解效果和更少的不良反应的治疗策略。
