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The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, a nociceptor and heat sensor) and melastatin 8 (TRPM8, a cold sensor) in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, and calcium imaging revealed that the expression and functional activity of TRPV1 were upregulated in rat dorsal root ganglion (DRG) neurons in PIPNP. Behavioral assessments using the von Frey and brush tests demonstrated that mechanical hyperalgesia in PIPNP was significantly inhibited by intraperitoneal or intrathecal administration of the TRPV1 antagonist capsazepine, indicating that TRPV1 played a key role in PIPNP. Conversely, the expression of TRPM8 protein decreased and its channel activity was reduced in DRG neurons. Furthermore, activation of TRPM8 via topical application of menthol or intrathecal injection of WS-12 attenuated the mechanical pain. Mechanistically, the TRPV1 activity triggered by capsaicin (a TRPV1 agonist) was reduced after menthol application in cultured DRG neurons, especially in the paclitaxel-treated group. These findings showed that upregulation of TRPV1 and inhibition of TRPM8 are involved in the generation of PIPNP, and they suggested that inhibition of TRPV1 function in DRG neurons via activation of TRPM8 might underlie the analgesic effects of menthol.<\/jats:p>","DOI":"10.3390\/ijms25115813","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T10:14:07Z","timestamp":1716804847000},"page":"5813","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Roles of Thermosensitive Transient Receptor Channels TRPV1 and TRPM8 in Paclitaxel-Induced Peripheral Neuropathic Pain"],"prefix":"10.3390","volume":"25","author":[{"given":"Wen-Wen","family":"Li","sequence":"first","affiliation":[{"name":"Department of Human Anatomy, Histology & Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Chun","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Histology & Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Histology & Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Wang","sequence":"additional","affiliation":[{"name":"Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, Peking University Health Science Center, Beijing 100191, China"},{"name":"PKU-IDG\/McGovern Institute for Brain Research, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5008-739X","authenticated-orcid":false,"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Histology & Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1529-8027.2008.00156.x","article-title":"Chemotherapy-induced neuropathy","volume":"13","author":"Windebank","year":"2008","journal-title":"J. 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