Chronic intractable pain affects a large proportion of cancer patients, especially those with metastatic bone disease. Blocking sensory afferents for cancer pain relief represents an attractive alternative to opioids and other drugs acting in the CNS in that sensory nerve blockers are not addictive and do not affect the mental state of the patient. A distinct subpopulation of sensory afferents expresses the capsaicin receptor TRPV1. Intrathecal resiniferatoxin, an ultrapotent capsaicin analog, ablates TRPV1-expressing nerve endings exposed to the cerebrospinal fluid, resulting in permanent analgesia in women with cervical cancer metastasis to the pelvic bone. High-dose capsaicin patches are effective pain killers in patients with chemotherapy-induced peripheral neuropathic pain. However, large gaps remain in our knowledge since the mechanisms by which cancer activates TRPV1 are essentially unknown. Most important, it is not clear whether or not sensory denervation mediated by TRPV1 agonists affects cancer progression. In a murine model of breast cancer, capsaicin desensitization was reported to accelerate progression. By contrast, desensitization mediated by resiniferatoxin was found to block melanoma growth. These observations imply that TRPV1 blockade for pain relief may be indicated for some cancers and contraindicated for others. In this review, we explore the current state of this field and compare the analgesic potential of TRPV1 antagonism and sensory afferent desensitization in cancer patients.
慢性顽固性疼痛影响着相当比例的癌症患者，尤其是那些伴有骨转移的患者。阻断感觉传入神经以缓解癌痛，相较于阿片类药物及其他作用于中枢神经系统的药物，展现出显著优势，因为感觉神经阻滞剂不会导致成瘾，也不会影响患者的精神状态。辣椒素受体TRPV1在特定的感觉传入神经亚群中表达。鞘内注射超强效辣椒素类似物树脂毒素，可消融暴露于脑脊液的TRPV1阳性神经末梢，从而为宫颈癌盆腔骨转移的女性患者带来持久镇痛效果。高剂量辣椒素贴片对于化疗引起的周围神经病理性疼痛患者是有效的镇痛手段。然而，我们对该领域的认知仍存在巨大空白，因为癌症激活TRPV1的机制基本上尚属未知。最重要的是，目前尚不清楚由TRPV1激动剂介导的感觉神经去神经化是否会影响癌症进展。在乳腺癌小鼠模型中，有报道称辣椒素脱敏会加速疾病进展。相反，树脂毒素介导的脱敏则被发现能够抑制黑色素瘤的生长。这些观察结果表明，为缓解疼痛而进行的TRPV1阻断可能适用于某些癌症，而对另一些癌症则可能禁忌。在本综述中，我们探讨了该领域的现状，并比较了TRPV1拮抗与感觉传入神经脱敏在癌症患者中的镇痛潜力。
肿瘤(癌症)患者之家