title: Oxaliplatin treatment changes the function of sensory nerves in rats.
abstract: Oxaliplatin (L-OHP) is a platinum-based chemotherapy drug, used in standard treatment of colorectal cancer. L-OHP frequently causes acute peripheral neuropathies. These adverse effects limit cancer therapy with L-OHP. The present study was designed to reveal the changes in sensory nerve function in L-OHP-injected rats. Mechanical static allodynia, dynamic allodynia, and cold allodynia were evaluated using the von Frey test, brush test, and acetone test, respectively. Sensory nerve fiber responsiveness was measured using a Neurometer. The fifth lumbar ventral root was sectioned to record multi-unit efferent discharges. Single intraperitoneal administration of L-OHP induced mechanical static allodynia, dynamic allodynia, and cold allodynia in Wistar/ST rats. The thresholds for paw withdrawal induced by 2000 Hz (Aβ-fiber) and 5 Hz (C-fiber), but not 250 Hz (Aδ-fiber) sine-wave electrical stimulation were reduced in L-OHP-treated rats. Multi-unit efferent discharges were increased by mechanical stimulation using a von Frey filament applied to the plantar surface of the hindpaw. The discharges during and after stimulation were increased in the L-OHP-treated rats. Cold stimulation, but not brush stimulation, increased the discharges in L-OHP-treated rats. These results suggest that sensitization of Aβ- and C-fibers, but not Aδ-fibers, contributes to the development of L-OHP-induced mechanical and cold allodynia.
authors.affiliation: Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan; Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan; Laboratory of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ono
authors.affiliation: Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kume
authors.affiliation: Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan; Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan. Electronic address: ohsawa@phar.nagoya-cu.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ohsawa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D059225:Nociception / Q000187:drug effects / Q000502:physiology; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology; D010812:Physical Stimulation; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin
keywords: Efferent discharge; Neurometer; Neuropathic pain; Oxaliplatin (L-OHP); Sensory nerve