title: Paclitaxel-induced peripheral neuropathy increases substance P release in rat spinal cord.
abstract: Peripheral neuropathy is a common adverse effect of paclitaxel treatment. The major dose-limiting side effect of paclitaxel is peripheral sensory neuropathy, which is characterized by painful paresthesia of the hands and feet. To analyze the contribution of substance P to the development of paclitaxel-induced mechanical hyperalgesia, substance P expression in the superficial layers of the rat spinal dorsal horn was analyzed after paclitaxel treatment. Behavioral assessment using the von Frey test and the paw thermal test showed that intraperitoneal administration of 2 and 4mg/kg paclitaxel induced mechanical allodynia/hyperalgesia and thermal hyperalgesia 7 and 14 days after treatment. Immunohistochemistry showed that paclitaxel (4mg/kg) treatment significantly increased substance P expression (37.6±3.7% on day 7, 43.6±4.6% on day 14) in the superficial layers of the spinal dorsal horn, whereas calcitonin gene-related peptide (CGRP) expression was unchanged. Moreover, paclitaxel (2 and 4mg/kg) treatment significantly increased substance P release in the spinal cord on day 14. These results suggest that paclitaxel treatment increases release of substance P, but not CGRP in the superficial layers of the spinal dorsal horn and may contribute to paclitaxel-induced painful peripheral neuropathy.
authors.affiliation: Departments of Medicinal Pharmacology, Showa Pharmaceutical University, 3-3165 Higashitamagawagakuen, Machida, Tokyo 194-8543, Japan.
authors.forename: Terumasa
authors.initials: T
authors.lastname: Chiba
authors.affiliation: Departments of Medicinal Pharmacology, Showa Pharmaceutical University, 3-3165 Higashitamagawagakuen, Machida, Tokyo 194-8543, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oka
authors.affiliation: Departments of Pharmacology, Showa Pharmaceutical University, 3-3165 Higashitamagawagakuen, Machida, Tokyo 194-8543, Japan.
authors.forename: Toshie
authors.initials: T
authors.lastname: Kambe
authors.affiliation: Departments of Pharmaceutics and Biopharmaceutics Showa Pharmaceutical University, 3-3165 Higashitamagawagakuen, Machida, Tokyo 194-8543, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Koizumi
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Ohu University, 31-1 Tomitamachi, Koriyama, Fukushima 963-8611, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Abe
authors.affiliation: Department of Pharmacy, Cancer Institute Hospital, 3-10-6 Ariake, Koto-Ku, Tokyo 135-8550, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Departments of Developmental Education, Showa Pharmaceutical University, 3-3165 Higashitamagawagakuen, Machida, Tokyo 194-8543, Japan.
authors.forename: Iku
authors.initials: I
authors.lastname: Utsunomiya
authors.affiliation: Departments of Medicinal Pharmacology, Showa Pharmaceutical University, 3-3165 Higashitamagawagakuen, Machida, Tokyo 194-8543, Japan. Electronic address: taguchi_k@mac.com.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Taguchi
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D017239:Paclitaxel / Q000009:adverse effects*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*
chemical_list: D018015:Receptors, Calcitonin Gene-Related Peptide; D013373:Substance P; D017239:Paclitaxel
keywords: Calcitonin gene-related peptide; Paclitaxel; Peripheral neuropathic pain; Spinal cord; Substance P