title: Blocking PAR2 attenuates oxaliplatin-induced neuropathic pain via TRPV1 and releases of substance P and CGRP in superficial dorsal horn of spinal cord.
abstract: Oxaliplatin (OXL) is a third-generation chemotherapeutic agent commonly used to treat metastatic digestive tumors; however, neuropathic pain is one of the main limiting complications of OXL. The purpose of this study was to examine the underlying mechanisms by which neuropathic pain is induced by OXL in a rat model. Our results demonstrated that blocking spinal proteinase-activated receptor 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) attenuated pain responses evoked by mechanical stimulation and decreased the releases of substance P and CGRP in the superficial dorsal horn of the spinal cord. The attenuating effect on mechanical pain was significantly smaller in OXL-rats than that in control rats. Blocking PAR2 also attenuated a heightened cold sensitivity evoked by OXL; whereas blocking TRPV1 had little effects on OXL-evoked hypersensitive cold response. Our data also showed that OXL increased the protein expressions of PAR2 and TRPV1 in the superficial dorsal horn. In addition, blocking PAR2 decreased TRPV1 expression in OXL-rats. Overall, our data suggest that upregulated expression of PAR2 in the superficial dorsal horn contributes to mechanical hyperalgesia and cold hypersensitivity; whereas amplified TRPV1 plays a role in regulating mechanical hyperalgesia, but not cold hypersensitivity after administration of OXL. We further suggest that TRPV1 is likely one of the signaling pathways for PAR2 to play a role in regulating OXL-induced neuropathic pain.
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China; Tongji Medical College, Wuhan, Hubei, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China; Tongji Medical College, Wuhan, Hubei, China.
authors.forename: Zhi-Fa
authors.initials: ZF
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China; Tongji Medical College, Wuhan, Hubei, China.
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Liao
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China; Tongji Medical College, Wuhan, Hubei, China.
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China; Tongji Medical College, Wuhan, Hubei, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China; Tongji Medical College, Wuhan, Hubei, China. Electronic address: wangxueren@hotmail.com.
authors.forename: Xue-Ren
authors.initials: XR
authors.lastname: Wang
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D056587:Cryopyrin-Associated Periodic Syndromes / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D009437:Neuralgia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009944:Organoplatinum Compounds / Q000009:adverse effects; D000077150:Oxaliplatin; D051381:Rats; D017208:Rats, Wistar; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D009944:Organoplatinum Compounds; D044464:Receptor, PAR-2; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D000077150:Oxaliplatin; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide
keywords: Neuropathic pain; Oxaliplatin; PAR2; TRPV1