Opioid and cannabinoid synergy in a mouse neuropathic pain model.

BACKGROUND AND PURPOSE:

Clinical studies have reported that pan-cannabinoid receptor agonists may have efficacy in neuropathic pain states and that this might be enhanced by co-administration with opioids. While cannabinoid-opioid analgesic synergy has been demonstrated in animal models of acute pain, it has not been examined in neuropathic pain models. We examined the effect of combination treatment with cannabinoid and opioid receptor agonists on allodynia and side-effects in a nerve injury induced neuropathic pain model.

EXPERIMENTAL APPROACH:

C57BL/6 mice were subjected to chronic constriction injury (CCI) of the sciatic nerve. The effect of systemic administration of morphine and the pan-cannabinoid receptor agonist WIN55212 and allodynia and side effects was examined at 7 – 10 days post-CCI surgery. Isobolographic analysis was used to determine whether combination effects were synergistic.

KEY RESULTS:

The opioid agonist morphine reduced CCI-induced mechanical and cold allodynia, and produced motor incoordination, in a dose dependent manner. WIN55212 reduced CCI-induced allodynia, and produced motor incoordination, catalepsy and sedation, in a dose dependent manner, as we have observed previously. When administered together, WIN55212 and morphine reduced allodynia in a synergistic manner, but had only an additive effect on motor incoordination.

CONCLUSIONS AND IMPLICATIONS:

These findings indicate that combination administration of non-selective opioid and cannabinoid receptor agonists synergistically reduces nerve injury induced allodynia, while producing side-effects in an additive manner. This suggests that combination treatment has an improved anti-allodynic potency and therapeutic index in a neuropathic pain model.
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