Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy.
Department of Biology, Unit of Cell and Developmental Biology, University of Pisa, Pisa, Italy.
Br J Pharmacol. 2024 Dec;181(23):4859-4873. doi: 10.1111/bph.17318. Epub 2024 Sep 5.
The oxidant sensor transient receptor potential ankyrin 1 (TRPA1) channel expressed by Schwann cells (SCs) has recently been implicated in several models of neuropathic pain in rodents. Here we investigate whether the pro-algesic function of Schwann cell TRPA1 is not limited to mammals by exploring the role of TRPA1 in a model of chemotherapy-induced peripheral neuropathy (CIPN) in zebrafish larvae.
We used zebrafish larvae and a mouse model to test oxaliplatin-evoked nociceptive behaviours. We also performed a TRPA1 selective silencing in Schwann cells both in zebrafish larvae and mice to study their contribution in oxaliplatin-induced CIPN model.
We found that zebrafish larvae and zebrafish TRPA1 (zTRPA1)-transfected HEK293T cells respond to reactive oxygen species (ROS) with nociceptive behaviours and intracellular calcium increases, respectively. TRPA1 was found to be co-expressed with the Schwann cell marker, SOX10, in zebrafish larvae. Oxaliplatin caused nociceptive behaviours in zebrafish larvae that were attenuated by a TRPA1 antagonist and a ROS scavenger. Oxaliplatin failed to produce mechanical allodynia in mice with Schwann cell TRPA1 selective silencing (Plp1-Trpa1 mice). Comparable results were observed in zebrafish larvae where TRPA1 selective silencing in Schwann cells, using the specific Schwann cell promoter myelin basic protein (MBP), attenuated oxaliplatin-evoked nociceptive behaviours.
These results indicate that the contribution of the oxidative stress/Schwann cell/TRPA1 pro-allodynic pathway to neuropathic pain models seems to be conserved across the animal kingdom.
施旺细胞（SCs）表达的氧化剂传感器瞬时受体电位锚蛋白 1（TRPA1）通道最近被认为与啮齿动物几种神经病理性疼痛模型有关。在这里，我们通过研究 TRPA1 在斑马鱼幼虫化疗诱导的周围神经病（CIPN）模型中的作用，来探讨 Schwann 细胞 TRPA1 的致痛功能是否不仅限于哺乳动物。
我们使用斑马鱼幼虫和小鼠模型来测试奥沙利铂引起的痛觉行为。我们还在斑马鱼幼虫和小鼠中对 Schwann 细胞中的 TRPA1 进行了选择性沉默，以研究其在奥沙利铂诱导的 CIPN 模型中的作用。
我们发现，斑马鱼幼虫和转染了斑马鱼 TRPA1（zTRPA1）的 HEK293T 细胞分别对活性氧（ROS）产生痛觉行为和细胞内钙增加反应。TRPA1 与 Schwann 细胞标志物 SOX10 在斑马鱼幼虫中共同表达。奥沙利铂引起的斑马鱼幼虫痛觉行为可被 TRPA1 拮抗剂和 ROS 清除剂减弱。在 Schwann 细胞 TRPA1 选择性沉默（Plp1-Trpa1 小鼠）的小鼠中，奥沙利铂未能引起机械性痛觉过敏。在 Schwann 细胞中使用特异性 Schwann 细胞启动子髓鞘碱性蛋白（MBP）进行的 TRPA1 选择性沉默的斑马鱼幼虫中，也观察到了类似的结果，减轻了奥沙利铂引起的痛觉行为。
这些结果表明，氧化应激/ Schwann 细胞/TRPA1 致痛通路对神经病理性疼痛模型的贡献似乎在整个动物界都是保守的。
