title: Possible involvement of the Sigma-1 receptor chaperone in chemotherapeutic-induced neuropathic pain.
abstract: Previous studies have shown that ligands of the sigma-1 receptor chaperone (Sig-1R) regulate pain-related behaviors. Clinical use of chemotherapeutics is often compromised due to their adverse side effects, particularly those related to neuropathy. Previous studies have shown that repeated administration of oxaliplatin and paclitaxel produces neuropathy in rodents. Therefore, the aim of the present study was to clarify the involvement of the Sig-1R in chemotherapeutic-induced neuropathy by examining the effects of oxaliplatin and paclitaxel on the Sig-1R levels in the spinal cord, and by examining the effects of Sig-1R agonist and antagonist on oxaliplatin- and paclitaxel-induced neuropathy in rats. Chemotherapeutic-induced neuropathic pain was accompanied by a significant reduction of the Sig-1R level in the spinal cord. Furthermore, the administration of paclitaxel to CHO cells that stably overexpressed Sig-1Rs induced the clustering of Sig-1Rs. We also found that the Sig-1R agonist SA4503 potently inhibited the neuropathy induced by oxaliplatin- and paclitaxel, whereas this action was abolished by the Sig-1R antagonist NE-100. These results suggest that the reduction of Sig-1R activity is involved in chemotherapeutic-induced neuropathy, and the Sig-1R agonist SA4503 could serve as a potential candidate for the treatment of chemotherapeutic-induced neuropathy.
authors.affiliation: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors.forename: Mori
authors.initials: M
authors.lastname: Tomohisa
authors.affiliation: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors.forename: Ohya
authors.initials: O
authors.lastname: Junpei
authors.affiliation: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors.forename: Masumoto
authors.initials: M
authors.lastname: Aki
authors.affiliation: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors.forename: Harumiya
authors.initials: H
authors.lastname: Masato
authors.affiliation: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors.forename: Fukase
authors.initials: F
authors.lastname: Mika
authors.affiliation: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors.forename: Yoshizawa
authors.initials: Y
authors.lastname: Kazumi
authors.affiliation: Seiwakai Nishikawa Hospital, Shimane, Japan.
authors.forename: Hayashi
authors.initials: H
authors.lastname: Teruo
authors.affiliation: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors.forename: Suzuki
authors.initials: S
authors.lastname: Tsutomu
mesh_terms: D000818:Animals; D000840:Anisoles / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000633:toxicity*; D015153:Blotting, Western; D016466:CHO Cells; D003412:Cricetulus; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D009437:Neuralgia / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000633:toxicity*; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000633:toxicity*; D010879:Piperazines / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018689:Sensory System Agents / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014110:Touch; D014162:Transfection; D000097605:Sigma-1 Receptor
chemical_list: D000840:Anisoles; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D017239:Paclitaxel; D010879:Piperazines; D011437:Propylamines; D017480:Receptors, sigma; D018689:Sensory System Agents; D000097605:Sigma-1 Receptor; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; C101789:SA 4503
keywords: SA4503; chemotherapeutic; neuropathic pain; sigma-1 receptor chaperone