Model of methadone-induced hyperalgesia in rats and effect of memantine

Justin Hay, Jahangir Kaboutari, Jason White, Abdallah Salem, Rodney Irvine

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    15 Citations (Scopus)


    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 1 mg/kg/day methadone (n = 6), or saline placebo (n = 6) (0.51 μl/h). A separate cohort of rats received either methadone 1 mg/kg/day (n = 8) or methadone 1 mg/kg/day with 20 mg/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.

    Original languageEnglish
    Pages (from-to)229-233
    Number of pages5
    JournalEuropean Journal of Pharmacology
    Issue number2-3
    Publication statusPublished - 25 Jan 2010


    • Hyperalgesia
    • Memantine
    • Methadone
    • Pain


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