Interaction between intrathecal morphine and glutamate receptor antagonists in formalin test

The analgesic interaction between intrathecally administered morphine and t he NMDA receptor antagonist, ((+/-)-2-amino-5-phosphonopentanoic acid; AP-5 ), the NMDA receptor glycine site antagonist, (5-nitro-6,7-dichloro-2,3-qui noxaline dion; ACEA 1021), or the AMPA (alpha-amino-3-hydroxy-5-methylisoxa zole-4-propionic acid) receptor antagonist (ACEA 2752) in the formalin test was investigated with a rat model of chronic lumbar intrathecal catheteriz ation. After obtaining dose-response curves for each agent, combinations of morphine and AP-5, ACEA 1021 or ACEA 2752 were tested for their effect on the number of flinches in the formalin test and for associated side-effects , such as motor disturbances, flaccidity, and agitation/allodynia. Using is obolographic analyses, a potent analgesic synergy was observed with decreas ed side-effects between morphine and ACEA 2752 or AP-5. ACEA 1021 increased the analgesic effect of low-dose morphine. Spinal mu-opioid receptor activ ation and NMDA or AMPA receptor antagonism showed a synergistic antinocicep tion against tonic pain. These results suggest an important direction in th e management of inflammatory pain. (C) 2000 Elsevier Science B.V. All right s reserved.