Sensitization of TRPV1 receptors by TNF‑α orchestrates the development of vincristine‑induced pain

Wang,Ying; Feng,Chenyang; He,Haoying; He,Jinjin; Wang,Jun; Li,Xiaomin; Wang,Shasha; Li,Wei; Hou,Jiuzhou; Liu,Tong; Fang,Dong; Xie,Song‑Qiang

doi:10.3892/ol.2018.7986

Sensitization of TRPV1 receptors by TNF‑α orchestrates the development of vincristine‑induced pain

Authors:
- Ying Wang
- Chenyang Feng
- Haoying He
- Jinjin He
- Jun Wang
- Xiaomin Li
- Shasha Wang
- Wei Li
- Jiuzhou Hou
- Tong Liu
- Dong Fang
- Song‑Qiang Xie
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Affiliations: Department of Medical Imaging, The First Affiliated Hospital of Henan University, Kaifeng, Henan 475001, P.R. China, Institute of Chemical Biology, College of Pharmacy, Henan University, Kaifeng, Henan 475004, P.R. China, Department of Clinic Pharmacy, The First Affiliated Hospital of Henan University, Kaifeng, Henan 475001, P.R. China
Published online on: February 7, 2018 https://doi.org/10.3892/ol.2018.7986
Pages: 5013-5019
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Vincristine is one of the most common anticancer drugs clinically employed in the treatment of various malignancies. A major side effect associated with vincristine is the development of neuropathic pain, which is not readily relieved by available analgesics. Although efforts have been made to identify the pathogenesis of vincristine‑induced neuropathic pain, the mechanisms underlying its pathogenesis have not been fully elucidated. In the present study, a neuropathic pain model was established in Sprague‑Dawley rats by intraperitoneal injection of vincristine sulfate. The results demonstrated that vincristine administration induced the upregulation of transient receptor potential cation channel subfamily V member 1 (TRPV1) protein expression and current density in dorsal root ganglion (DRG) nociceptive neurons. Consistently, inhibition of TRPV1 with capsazepine alleviated vincristine‑induced mechanical allodynia and thermal hyperalgesia in rats. Furthermore, vincristine administration induced the upregulation of tumor necrosis factor (TNF)‑α production in DRGs, and inhibition of TNF‑α synthesis with thalidomide in vivo reversed TRPV1 protein expression, as well as pain hypersensitivity induced by vincristine in rats. The present results suggested that TNF‑α could sensitize TRPV1 by promoting its expression, thus leading to mechanical allodynia and thermal hyperalgesia in vincristine‑treated rats. Taken together, these findings may enhance our understanding of the pathophysiological mechanisms underlying vincristine‑induced pain.

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