Laboratorio de Dolor en Cáncer, Instituto de Investigaciones en Medicina Traslacional CONICET - Universidad Austral, Av. Pte. Perón 1500, B1629AHJ Pilar, Buenos Aires, Argentina.
Laboratorio de Dolor en Cáncer, Instituto de Investigaciones en Medicina Traslacional CONICET - Universidad Austral, Av. Pte. Perón 1500, B1629AHJ Pilar, Buenos Aires, Argentina; Facultad de Ciencias Biomédicas, Universidad Austral, Av. Pte. Perón 1500, B1629AHJ Pilar, Buenos Aires, Argentina.
Neurosci Lett. 2022 Sep 25;788:136863. doi: 10.1016/j.neulet.2022.136863. Epub 2022 Sep 5.
Transient receptor potential (TRP) channels are involved in the development of oxaliplatin-induced neuropathic pain, a frequent and debilitating side effect of cancer therapy. Here we explored whether oxaliplatin-induced changes in the expression of TRP channels, as well as the development of pain-related behaviours, differed between male and female animals. Adult rats were injected with oxaliplatin or saline and mechanical and cold allodynia were evaluated using Von Frey and Choi Tests. The mRNA levels of TRPV1, TRPM8 and TRPA1 were assessed in lumbar ganglia and spinal cord by using real time RT-PCR. Oxaliplatin administration induced mechanical and cold hypersensitivity and allodynia in both sexes, with more severe responses to cold stimulation detected in females. Oxaliplatin also induced a significant increase in the expression of TRPV1, TRPM8 and TRPA1 in lumbar dorsal root ganglia. Interestingly, while TRPV1 and TRPA1 upregulation showed no sex difference, the increase in TRPM8 mRNA levels was more pronounced in female ganglia, correlating with the increased sensitivity to innocuous cold stimuli observed in females. TRPV1 and TRPM8 were also found to be upregulated in the spinal cord of animals of both sexes. Our results reveal previously undescribed changes in the expression of TRP channels occurring in peripheral ganglia and spinal cord of both male and female oxaliplatin-treated animals, with some of these changes exhibiting sex-related differences that could underlie the development of sex-specific patterns of pain-related behaviours.
瞬时受体电位 (TRP) 通道参与奥沙利铂诱导的神经性疼痛的发展，这是癌症治疗中常见且使人虚弱的副作用。在这里，我们探讨了奥沙利铂诱导的 TRP 通道表达变化以及相关疼痛行为的发展是否在雄性和雌性动物之间存在差异。成年大鼠接受奥沙利铂或生理盐水注射，并使用 Von Frey 和 Choi 测试评估机械和冷感觉过敏。通过实时 RT-PCR 评估腰椎神经节和脊髓中 TRPV1、TRPM8 和 TRPA1 的 mRNA 水平。奥沙利铂给药诱导了两性的机械和冷感觉过敏和痛觉过敏，女性对冷刺激的反应更为严重。奥沙利铂还诱导 TRPV1、TRPM8 和 TRPA1 在腰椎背根神经节中的表达显著增加。有趣的是，虽然 TRPV1 和 TRPA1 的上调没有性别差异，但 TRPM8 mRNA 水平的增加在雌性神经节中更为明显，与女性观察到的对无害冷刺激的敏感性增加相关。TRPV1 和 TRPM8 也在两性动物的脊髓中上调。我们的研究结果揭示了奥沙利铂处理的雄性和雌性动物外周神经节和脊髓中以前未描述的 TRP 通道表达变化，其中一些变化表现出与性别相关的差异，这可能是导致特定性别疼痛相关行为模式发展的基础。
