2007, Number 5
Anti-hyperalgesic effect of one combination of morphine and gabapentin in neuropathic pain induced by chronic constriction injury in rat
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ABSTRACTBackground: Neuropathic pain is associated with disease or injury to the peripheral or central nervous system, which is considered particularly difficult to treat due to its diverse etiology and underlying physiopathological mechanisms. Recent experimental and clinical data support the potential of pharmacotherapy using a combination of drugs for neuropathic pain.
Methods: In order to assess a possible synergistic anti-hyperalgesic interaction, the anti-hyperalgesic effects of morphine and gabapentin, single-dose administered either separately or in combination, were determined using the von Frey test in a rat model of neuropathic pain (Bennett model).
Results: Time course analysis showed that morphine (3.2 mg/kg SC) and gabapentin (17.8 mg/kg SC) individually reached their maximum effect at 60 min after treatment, producing an anti-hyperalgesic effect of 51.7 ± 10.5 % and 55.0 ± 11.7 %, respectively, whereas the combination morphine + gabapentin (3.2 + 17.8 mg/kg SC) produced an almost total anti-hyperalgesic effect at 30 min (96.7 ± 2.1 %) and at 60 min showed 100 % anti-hyperalgesia. This anti-hyperalgesic effect remained during 180 min of observation. Analysis of global effects as area under the curve of time course showed that the nature of the anti-hyperalgesic interaction of the analyzed dose had an additive effect. There was no significant difference observed in the theoretical sum of anti-hyperalgesic effect produced by each drug alone (225.4 ± 29.1 area units, au) compared with the corresponding effects produced by the combination of drugs (263.33 ± 3.3 au).
Conclusions: These findings are useful in determining the type of interaction that these drugs produce using this combination ratio in neuropathic pain.
Hasson PT, Lacerenza M, Marchettini P. Aspects of clinical and experimental neuropathic pain: the clinical perspective. In: Hasson PT, Fields HL, Hill RG, Marchettini P, eds. Neuropathic Pain: Pathophysiology and Treatment. Progress in Pain Research and Management, Vol. 21. Seattle: IASP Press;2001. pp 1-18.