Baclofen and opioid interactions in mice could inform pain treatment methods.

With the current pressure to reduce opioid usage in the clinical setting, there is a call for the development of adjunct therapies. Although opioids remain the primary analgesic used in the treatment of moderate to severe pain, these drugs come with negative side effects, such as increased potential for abuse. The overlap in expression of opioid and GABA receptors suggests that the 2 systems may interact. Therefore, to investigate this interaction, our study used the GABAB receptor agonist, baclofen, because it has previously been used as a treatment for spasticity and addiction and has demonstrated weak analgesic properties. Our study focused on the interaction between baclofen and opioid analgesics regarding analgesic efficacy and abuse potential. Analgesia was assessed through hot plate testing and reward was assessed through conditioned place preference testing in outbred CD1 mice. These interactions were examined with morphine, methadone, oxycodone, and fentanyl using isobolographic analyses. All opioids tested with baclofen demonstrate synergism in analgesia and no consistent significant interactions in place preference conditioning. Together these data support the use of baclofen coupled with opioids to enhance the analgesia, with no concomitant increase in abuse liability and associated common side effects of opioid drugs. SIGNIFICANCE STATEMENT: The combination of the commonly prescribed drug, baclofen, and a variety of opioids exhibits a synergistic analgesic effect allowing for lower doses of opioids to be used for equivalent analgesic effect. Synergistic analgesia was seen without concomitant enhanced tolerance, constipation, or reward, and across species, suggesting a beneficial interaction for pain relief.