title: Neurotropin® relieves oxaliplatin-induced neuropathy via Gi protein-coupled receptors in the monoaminergic descending pain inhibitory system.
abstract: OBJECTIVE
  Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic peripheral neuropathies. We previously reported that repeated administration of neurotropin prevents oxaliplatin-induced mechanical allodynia by inhibiting axonal degeneration in rats. In the present study, we investigated the analgesic effect of a single administration of neurotropin on oxaliplatin-induced neuropathy in rats.
  
  
  METHODS
  Oxaliplatin (4mg/kg) was administered intraperitoneally twice a week for 4weeks. Cold hyperalgesia was assessed using the acetone test and mechanical allodynia was evaluated using the von Frey test.
  
  
  RESULTS
  Repeated injection of oxaliplatin induced cold hyperalgesia on day 5 and mechanical allodynia on day 28. A single administration of neurotropin transiently relieved both pain behaviors. The analgesic effect of neurotropin was inhibited by pretreatment with 5-HT1A, 5-HT2, 5-HT3, and α2 receptor antagonists and by monoamine depletion. Moreover, the analgesic effect of neurotropin was abolished by intrathecal injection of pertussis toxin, a Gi protein inhibitor.
  
  
  CONCLUSIONS
  These results suggest that neurotropin is effective in relieving oxaliplatin-induced neuropathy, and that Gi protein-coupled receptors in the monoaminergic descending pain inhibitory system may be involved in the analgesic effect of neurotropin. Neurotropin may have clinical potential for the treatment of oxaliplatin-induced neuropathies.
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Masuguchi
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Kawashiri
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ushio
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Ozawa
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Morita
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Ryozo
authors.initials: R
authors.lastname: Oishi
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: n-egashi@pharm.med.kyushu-u.ac.jp.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D008297:Male; D009437:Neuralgia / Q000139:chemically induced* / Q000188:drug therapy; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D011134:Polysaccharides / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000700:Analgesics; D009944:Organoplatinum Compounds; D011134:Polysaccharides; D043562:Receptors, G-Protein-Coupled; D000077150:Oxaliplatin; D012701:Serotonin; C010491:neurotropin
keywords: 6-Hydroxydopamine (PubChem CID: 4624); Allodynia; G(i) protein-coupled receptors; Ketanserin (PubChem CID: 3822); Monoamine; Neurotropin; Oxaliplatin; Oxaliplatin (PubChem CID: 5310940); Prazosin (PubChem CID: 4893); WAY100635 (PubChem CID: 5684); Yohimbine (PubChem CID: 8969); p-Chlorophenylalanine (PubChem CID: 26229)