Study of morphine tolerance at spinal level-approach to spinal plasticity-

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Male Sprague-Dawley rats were implanted lumber intrathecal catheters. Intrathecal injection of morphine 20 μg /10μl was repeated twice a day for 5 days. To measure withdrawal responses to noxious stimuli, radiant heating (RH) and paw pressure (PP) were applied to rat's paws. The threshold to non-noxious stimulus was measured using Semmes-Weinstein monofilament (SWM). Chronic morphine administration increased the responses to noxious and non-noxious stimuli, suggesting the spinal sensitization.Second study was designed to investigate the effect of ketamine, an NMDA receptor antagonist, on hypersensitive state induced by chronic morphine treatment. Morphine with/without ketamine was administered two times a day for 5 days. Combined ketamine reduced the hypersensitive state induced by morphine, suggesting that the NMDA receptor activation was involved in the spinal sensitization induced by chronic morphine.Third study was designed to investigate the effect of pretreatment of lidocaine to the hypersensitive responses induced by chronic morphine. The group injected lidocaine 10min before the morphine was compared to the group injected morphine alone. The pretreatment of lidocaine did not affect the hypersensitive responses to noxious and non-noxious stimuli.After the final measurement, rats were euthanized and taken spinal cords for electrophysiological study. A sliced spinal cord was placed on the MED probe for recording electric responses. It was difficult to compare the neuronal activities precisely between saline and morphine treated group, because of the poor recording from a sliced spinal cord.