Electrophysiologic analysis of preemptive effects of spinal opioids on N- methyl-D-aspartate receptor-mediated events

V. Chapman, J.E. Haley, A.H. Dickenson

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background: Spinal N-methyl-D-aspartate (NMDA) receptor-mediated mechanisms may contribute to reduced opioid sensitivity in conditions of pain. The effectiveness of spinal opioids in inhibiting NMDA-mediated nociceptive events was assessed with two models. In addition, opioid dose- response curves with preemptive administration were compared with early and late postadministrations. Methods: Dorsal horn nociceptive neuronal responses were recorded in the intact halothane anesthetized rat to acute repetitive C- fiber electrical stimulation (0.1 and 0.5 Hz) and to the peripheral injection of 5% formalin. At 0.5 Hz but not at 0.1 Hz, there was an enhanced C-fiber evoked response of dorsal horn neurons elicited by repetitive C-fiber stimulation (wind-up), which is mediated by the NMDA receptor. Formalin produced a biphasic response; the late protracted inflammatory phase was NMDA receptor-mediated. Results: With 0.5-Hz stimulation a large degree of wind- up was elicited; it was less sensitive to 5 μg morphine compared with the effect of the same dose on the residual wind-up elicited at 0.1 Hz. Preadministration and early postadministration of morphine were equieffective at inhibiting the second-phase formalin response. In contrast, administration of the fast-acting μ opioid, D-Ala-Gly-MePhe-Gly-ol, given late postadministration (during the second phase) was less effective than preadministration. Increasing the dose of D-Ala-Gly-MePHe-Gly-ol produced complete inhibitions. Conclusions: NMDA receptor-mediated neuronal responses, such as wind-up and the established second phase of the formalin response, are poorly responsive to opioids. Dose increases and preemptive opioids effectively inhibit these NMDA receptor-mediated events.
Original languageEnglish
Pages (from-to)1429-1435
Number of pages7
Issue number6
Publication statusPublished - 1 Jan 1994


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