title: Chronic administration of modafinil induces hyperalgesia in mice: reversal by L-NG-nitro-arginine methyl ester and 7-nitroindazole.
abstract: Modafinil [2-((diphenylmethyl) sulfinyl) acetamide] is a central nervous system stimulant. It has received considerable attention as a potential psychotropic agent in several psychiatric disorders. The current study was carried out to investigate the effect of modafinil after acute administration on animal models of pain in mice. Also, this study evaluated the effect of L-NG-nitroarginine methyl ester (L-NAME), 7-nitroindazole (7-NI) and naloxone following chronic administration of modafinil. Modafinil was administered in the doses of 50, 100 or 200 mg/kg once in acute study and it showed significantly increased tail-flick latency (tfl) and paw-licking latency. In formalin test modafinil (100 mg/kg) significantly reduced licking/biting time in both early and late phases in comparison to control. In chronic study, modafinil 100 mg/kg administered for 10 days, produced a progressive decrease in the reaction time (i.e., tfl/paw-licking latency) in comparison to day 1 values which started building up from day 4 and fully established at day 6, indicating hyperalgesic response. Prior administration of 7-NI (on day 7) and L-NAME (on day 10) prevented the hyperalgesic response while naloxone on day 10 did not have a significant effect on modafinil-induced hyperalgesia. These results demonstrate that modafinil has a potential role in pain as it exhibited antinociceptive effect after acute administration in a dose-dependent manner and on chronic administration it caused hyperalgesia. This hyperalgesia is reversed by nitric oxide synthase inhibitors, suggesting the possibility of involvement of nitric oxide pathway. Further studies are required to evaluate the role of modafinil in clinical pain.
authors.affiliation: Department of Pharmacology, University College of Medical Sciences and GTB Hospital, University of Delhi, Delhi 110095, India.
authors.forename: Rachna
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Department of Pharmacology, Lady Hardinge Medical College & Smt. S.K. Hospital, New Delhi 110001, India. Electronic address: lkg71@rediffmail.com.
authors.forename: Lalit Kumar
authors.initials: LK
authors.lastname: Gupta
authors.affiliation: Department of Pharmacology, University College of Medical Sciences and GTB Hospital, University of Delhi, Delhi 110095, India.
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Bhattacharya
mesh_terms: D000700:Analgesics / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use; D005557:Formaldehyde; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced* / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D000077408:Modafinil; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism
chemical_list: D000700:Analgesics; D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D007191:Indazoles; D005557:Formaldehyde; D009270:Naloxone; D019001:Nitric Oxide Synthase; D000077408:Modafinil; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester
keywords: 7-Nitroindazole; Hyperalgesia; Modafinil; Nitric oxide; l-NAME