Postoperative pain is a complex clinical condition that is still inadequately managed. Opioids remain the first line agents for the management of postoperative pain despite their side effects. Combination treatment with non-opioid agents that act at different sites within the central and peripheral nervous system might lead to synergistic effects, thus minimizing the necessary morphine dose and correspondingly its side effects.
In a blinded, randomized, 16 arms study, the pharmacodynamic interactions of morphine and gabapentin were evaluated. In the plantar incision model in the rat, a series of hindpaw withdrawal thresholds, after subcutaneous administration of morphine (0, 1, 3 and 7 mg/kg), gabapentin (0, 10, 30 and 100 mg/kg) or their combination (9 combinations of the above doses) were obtained using an electronic von Frey device. Surface of synergistic interaction (SSI) analysis was used to detect the synergistic effects.
Five combinations resulted in synergistic antihyperalgesic effects whereas four combinations produced additive antihyperalgesic effects. Increase of observed response in comparison to the theoretical additive response ranged between 46.7 and 85.8 % for the synergistic doses.
Combination of morphine and gabapentin resulted in synergistic antihyperalgesic effects in a preclinical model of postoperative pain. This might indicate that there is a high potential for gabapentin and morphine to be used in the clinic, in order to optimize postoperative pain management and minimize side effects of morphine.