Potentiation of PIEZO2 mechanically-activated currents in sensory neurons mediates vincristine-induced mechanical hypersensitivity

Mingli Duan; Yurui Jia; Lifang Huo; Yiting Gao; Jia Wang; Wei Zhang; Zhanfeng Jia

Acta Pharmaceutica Sinica B (Aug 2023)

Potentiation of PIEZO2 mechanically-activated currents in sensory neurons mediates vincristine-induced mechanical hypersensitivity

Mingli Duan,
Yurui Jia,
Lifang Huo,
Yiting Gao,
Jia Wang,
Wei Zhang,
Zhanfeng Jia

Affiliations

Mingli Duan: Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China; Center of Innovative Drug Research and Evaluation, Institute of Medical Science and Health, Hebei Medical University, Shijiazhuang 050017, China; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang 050017, China; The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang 050017, China; The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Shijiazhuang 050017, China
Yurui Jia: Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China; Center of Innovative Drug Research and Evaluation, Institute of Medical Science and Health, Hebei Medical University, Shijiazhuang 050017, China; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang 050017, China; The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang 050017, China; The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Shijiazhuang 050017, China
Lifang Huo: Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China; Center of Innovative Drug Research and Evaluation, Institute of Medical Science and Health, Hebei Medical University, Shijiazhuang 050017, China; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang 050017, China; The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang 050017, China; The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Shijiazhuang 050017, China; Department of Pharmacology, Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China
Yiting Gao: Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China; Center of Innovative Drug Research and Evaluation, Institute of Medical Science and Health, Hebei Medical University, Shijiazhuang 050017, China; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang 050017, China; The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang 050017, China; The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Shijiazhuang 050017, China
Jia Wang: Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China; Center of Innovative Drug Research and Evaluation, Institute of Medical Science and Health, Hebei Medical University, Shijiazhuang 050017, China; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang 050017, China; The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang 050017, China; The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Shijiazhuang 050017, China
Wei Zhang: Department of Pharmacology, Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China; Center of Innovative Drug Research and Evaluation, Institute of Medical Science and Health, Hebei Medical University, Shijiazhuang 050017, China; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang 050017, China
Zhanfeng Jia: Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China; Center of Innovative Drug Research and Evaluation, Institute of Medical Science and Health, Hebei Medical University, Shijiazhuang 050017, China; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang 050017, China; The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang 050017, China; The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Shijiazhuang 050017, China; Corresponding author. Tel.: +86 311 86266343.

Journal volume & issue: Vol. 13, no. 8
pp. 3365 – 3381

Abstract

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Vincristine, a widely used chemotherapeutic agent for treating different cancer, often induces severe peripheral neuropathic pain. A common symptom of vincristine-induced peripheral neuropathic pain is mechanical allodynia and hyperalgesia. However, mechanisms underlying vincristine-induced mechanical allodynia and hyperalgesia are not well understood. In the present study, we show with behavioral assessment in rats that vincristine induces mechanical allodynia and hyperalgesia in a PIEZO2 channel-dependent manner since gene knockdown or pharmacological inhibition of PIEZO2 channels alleviates vincristine-induced mechanical hypersensitivity. Electrophysiological results show that vincristine potentiates PIEZO2 rapidly adapting (RA) mechanically-activated (MA) currents in rat dorsal root ganglion (DRG) neurons. We have found that vincristine-induced potentiation of PIEZO2 MA currents is due to the enhancement of static plasma membrane tension (SPMT) of these cells following vincristine treatment. Reducing SPMT of DRG neurons by cytochalasin D (CD), a disruptor of the actin filament, abolishes vincristine-induced potentiation of PIEZO2 MA currents, and suppresses vincristine-induced mechanical hypersensitivity in rats. Collectively, enhancing SPMT and subsequently potentiating PIEZO2 MA currents in primary afferent neurons may be an underlying mechanism responsible for vincristine-induced mechanical allodynia and hyperalgesia in rats. Targeting to inhibit PIEZO2 channels may be an effective analgesic method to attenuate vincristine-induced mechanical hypersensitivity.

Published in Acta Pharmaceutica Sinica B

ISSN: 2211-3835 (Print); 2211-3843 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/acta-pharmaceutica-sinica-b

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