title: Effect of paclitaxel on transient receptor potential vanilloid 1 in rat dorsal root ganglion.
abstract: Peripheral neuropathy is a common adverse effect of paclitaxel treatment. To analyze the contribution of transient receptor potential vanilloid 1 (TRPV1) in the development of paclitaxel-induced thermal hyperalgesia, TRPV1 expression in the rat dorsal root ganglion (DRG) was analyzed after paclitaxel treatment. Behavioral assessment using the tail-flick test showed that intraperitoneal administration of 2 and 4 mg/kg paclitaxel induced thermal hyperalgesia after days 7, 14, and 21. Paclitaxel-induced thermal hyperalgesia after day 14 was significantly inhibited by the TRP antagonist ruthenium red (3 mg/kg, s.c.) and the TRPV1 antagonist capsazepine (30 mg/kg, s.c.). Paclitaxel (2 and 4 mg/kg) treatment increased the expression of TRPV1 mRNA and protein in DRG neurons. Immunohistochemistry showed that paclitaxel (4 mg/kg) treatment increased TRPV1 protein expression in small and medium DRG neurons 14 days after treatment. Antibody double labeling revealed that isolectin B4-positive small DRG neurons co-expressed TRPV1. TRPV1 immunostaining was up-regulated in paw skin day 14 after paclitaxel treatment. Moreover, in situ hybridization histochemistry revealed that most of the TRPV1 mRNA-labeled neurons in the DRG were small or medium in size. These results suggest that paclitaxel treatment increases TRPV1 expression in DRG neurons and may contribute to functional peripheral neuropathic pain.
authors.affiliation: Department of Medicinal Pharmacology, Showa Pharmaceutical University, Machida, Tokyo, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hara
authors.forename: Terumasa
authors.initials: T
authors.lastname: Chiba
authors.forename: Kenji
authors.initials: K
authors.lastname: Abe
authors.forename: Akiko
authors.initials: A
authors.lastname: Makabe
authors.forename: Souichi
authors.initials: S
authors.lastname: Ikeno
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
authors.forename: Iku
authors.initials: I
authors.lastname: Utsunomiya
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Hama
authors.forename: Kyoji
authors.initials: K
authors.lastname: Taguchi
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D012430:Ruthenium Red; D017239:Paclitaxel