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.
尽管癌性疼痛具有独特且复杂的性质，不同离子通道的激活可能与疼痛的发生和维持相关。瞬时受体电位香草素4（TRPV4）是一种在感觉传入神经元中广泛表达的阳离子通道，该通道能被多种刺激激活，介导与炎症性疼痛和神经病理性疼痛相关的痛觉感知。本文重点综述了TRPV4在癌症病因学及癌症诱发疼痛机制中的作用。多项研究表明，给予TRPV4拮抗剂或敲低TRPV4表达可减轻化疗诱导的周围神经病变（CIPN）中的伤害性感受。尽管TRPV4通道参与癌性疼痛的证据尚不充分，但据报道，在分别将肿瘤细胞接种至骨髓腔、坐骨神经和舌部建立的癌症诱导骨痛（CIBP）、神经周围癌及口面部癌模型中，这些受体的表达均有所增强。对于确诊癌症的患者而言，有效的疼痛管理始终是亟待解决的难题，而现有指南尚未能提供基于机制的治疗方案。因此，研究靶向TRPV4调控、具有潜在镇痛作用的新型分子具有重要意义。识别此类药物有望开发出比现有镇痛药镇痛效果更佳、不良反应更少的治疗策略。
肿瘤(癌症)患者之家