Temperature-dependent enhancement of the antinociceptive effects of opioids in combination with gabapentin in mice

Prescription opioids and anticonvulsants such as gabapentin are often used as combination therapeutics for chronic as well as acute post-operative pain conditions although the effectiveness of such combinations may be dependent on the intensity of the pain state. To test the capacity of gabapentin to enhance opioid effectiveness in the presence of different thermal stimulus intensities, morphine, oxycodone and gabapentin were examined alone and in combination for antinociception in Swiss-Webster male mice using a hot-plate set to one of three temperature intensities (48.5 °C, 50.5 °C, 52.5 °C). Morphine and oxycodone produced significant dose- and stimulus intensity-dependent antinociception whereas gabapentin produced only modest antinociception. However, in combination, gabapentin enhanced the effectiveness of sub-antinociceptive doses of morphine and oxycodone and the gabapentin and oxycodone combinations were both dose- and temperature intensity-dependent. These results provide evidence that the effectiveness and magnitude of the interactions between gabapentin and opioids are dependent on the intensity of the pain stimulus in acute thermal pain states.