Combined systemic administration of the glycine/NMDA receptor antagonist, (+)-HA966 and morphine attenuates pain-related behaviour in a rat model of trigeminal neuropathic pain

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Abstract
E to the poor opioid sensitivity of this syndrome. We evaluated the effect of combined systemic administration of the functional antagonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor complex, (+)-(1-Hydroxy-3-aminopyrrolodine-2-one) ((+)-HA966) with morphine on mechanical allodynia-like behaviour in CCI-ION rats. Two weeks after surgery rats with a CCI-ION displayed mechanical hyperresponsiveness to von Frey filament stimulation of the vibrissal pad with a median at 0.217 g (95% confidence limits, 0.217–0.224) versus ≥ 12.5 g pre-operative. Administration of either (+)-HA966 (2.5 mg/kg s.c.) alone or morphine (1 mg/kg i.v.) alone was devoid of effects on the mechanical hyperresponsiveness. By contrast, combined administration of (+)-HA966 and morphine (0.25, 0.5 and 1 mg/kg i.v.) dose-dependently increased the mechanical response thresholds (peak-effects 0.745 g (0.745–0.745), 4.64 (3.3–8.7) and 12.5 g (8.4–12.5), respectively). This effect was prevented and reversed by naloxone (0.1 mg/kg i.v.). The drug combination produced no motor deficits in animals using the rotarod test. The present results indicate that combination therapy with NMDA/glycine receptor antagonists and morphine may be a useful approach for the clinical management of trigeminal neuropathic pain disorders....

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