PDF(Pubmed)
Abstract：
Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a shared burden for 68.1% of oncological patients undergoing chemotherapy with Paclitaxel (PTX). The symptoms are intense and troublesome, patients reporting paresthesia, loss of sensation, and dysesthetic pain. While current medications focus on decreasing the symptom intensity, often ineffective, no medication is yet recommended by the guidelines for the prevention of CIPN. Cannabinoids are an attractive option, as their neuroprotective features have already been demonstrated in neuropathies with other etiologies, by offering the peripheral neurons protection against toxic effects, which promotes analgesia. Methods: We aim to screen several new cannabinoids for their potential use as neuroprotective agents for CIPN by investigating the cellular toxicity profile and by assessing the potential neuroprotective features against PTX using a primary dorsal root ganglion neuronal culture. Results: Our study showed that synthetic cannabinoids JWH-007, AM-694 and MAB-CHMINACA and phytocannabinoids Cannabixir® Medium dried flowers (NC1) and Cannabixir® THC full extract (NC2) preserve the viability of fibroblasts and primary cultured neurons, in most of the tested dosages and time-points. The combination between the cannabinoids and PTX conducted to a cell viability of 70%-89% compared to 40% when PTX was administered alone for 48 h. When assessing the efficacy for neuroprotection, the combination between cannabinoids and PTX led to better preservation of neurite length at all tested time-points compared to controls, highly drug and exposure-time dependent. By comparison, the combination of the cannabinoids and PTX administered for 24 h conducted to axonal shortening between 23% and 44%, as opposed to PTX only, which shortened the axons by 63% compared to their baseline values. Discussion and Conclusion: Cannabinoids could be potential new candidates for the treatment of paclitaxel-induced peripheral neuropathy; however, our findings need to be followed by additional tests to understand the exact mechanism of action, which would support the translation of the cannabinoids in the oncological clinical practice.
摘要：
简介：化疗诱导的周围神经病变（CIPN）是68.1％接受紫杉醇（PTX）化疗的肿瘤患者的共同负担。症状强烈而麻烦，报告感觉异常的患者，失去感觉，和美感疼痛。虽然目前的药物专注于降低症状强度，往往是无效的,预防CIPN的指南还没有推荐药物治疗.大麻是一个有吸引力的选择,因为它们的神经保护特征已经在其他病因的神经病中得到证实，通过保护外周神经元免受毒性作用，促进镇痛。方法：我们旨在通过研究细胞毒性特征并通过使用原代背根神经节神经元培养物评估针对PTX的潜在神经保护特征，筛选几种新的大麻素作为CIPN的神经保护剂的潜在用途。结果：我们的研究表明，合成大麻素JWH-007，AM-694和MAB-CHMINACA和植物大麻素Cannabixir®中等干花（NC1）和Cannabixir®THC全提取物（NC2）保留成纤维细胞和原代培养神经元的活力，在大多数测试的剂量和时间点。大麻素和PTX之间的组合进行到70％-89％的细胞活力相比，当PTX单独施用48小时时，40％。当评估神经保护的功效时，与对照组相比，大麻素和PTX之间的组合在所有测试时间点都能更好地保留神经突长度，高度依赖药物和暴露时间。相比之下,大麻素和PTX的组合施用24小时，轴突缩短23％至44％，与仅PTX相反，与基线值相比，轴突缩短了63%。讨论与结论：大麻素可能是治疗紫杉醇引起的周围神经病变的潜在新候选药物；然而，我们的发现需要进行额外的测试以了解确切的作用机制，这将支持大麻素在肿瘤临床实践中的翻译。
