title: Model of methadone-induced hyperalgesia in rats and effect of memantine.
abstract: Methadone used for opioid dependence therapy is associated with increased pain sensitivity. This study aimed to investigate whether methadone administration lowers nociceptive threshold in adult male Sprague-Dawley (SD) rats, and if this threshold could be altered by the NMDA receptor antagonist memantine. Rats were implanted with osmotic pumps delivering 1mg/kg/day methadone (n=6), or saline placebo (n=6) (0.51 microl/h). A separate cohort of rats received either methadone 1mg/kg/day (n=8) or methadone 1mg/kg/day with 20mg/kg/day memantine (n=8). Nociception was measured by the Hargreave's paw withdrawal test. Baseline nociception was measured on day 0 prior to osmotic pump implantation and was measured daily for the following 21 days. Osmotic pumps were removed following nociceptive testing on day 14. Methadone only treated rats had a mean paw withdrawal latency significantly lower than the corresponding values for saline on days 8, 9, 10, 11, 12, 14, and 17 (P<0.05). At all other time points the mean paw withdrawal latency was not significantly different from saline (P>0.05). Paw withdrawal latency of rats treated with methadone co-administered with memantine did not differ significantly compared to methadone only (P>0.05). This demonstrates that methadone induces hyperalgesia in the SD rat yet this hyperalgesia resolves following discontinuation of methadone administration. Furthermore, memantine does not alter the development of methadone-induced hyperalgesia.
authors.affiliation: Discipline of Pharmacology, Level 5, Medical School North, University of Adelaide, SA 5005, Australia. justin.hay@alumni.adelaide.edu.au
authors.forename: Justin L
authors.initials: JL
authors.lastname: Hay
authors.forename: Jahangir
authors.initials: J
authors.lastname: Kaboutari
authors.forename: Jason M
authors.initials: JM
authors.lastname: White
authors.forename: Abdallah
authors.initials: A
authors.lastname: Salem
authors.forename: Rod
authors.initials: R
authors.lastname: Irvine
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008559:Memantine / Q000494:pharmacology* / Q000627:therapeutic use; D008691:Methadone / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D008691:Methadone; D008559:Memantine