Synergistic interaction between butorphanol and dexmedetomidine in antinociception

Opioid analgesics and the α₂-adrenergic receptor (α₂AR) agonists are found to produce synergistic antinociception when administered in combination. In this study interactions between butorphanol and dexmedetomidine were investigated in the thermal pain and autonomous locomotor activity. Butorphanol and dexmedetomidine were administered subcutaneously alone and in combination in a fixed-dose ratio (3:1) to assess the antinociceptive and sedative responses. Butorphanol produced antinociception in the hot-plate test via three major opioid receptor subtypes, i.e. MORs, KORs and DORs, while in the tail-immersion test the antinociception was produced by MORs and KORs, whereas dexmedetomidine exhibited antinociception by α₂ARs in both tests. They exhibited dose- and time-dependent antinociception and inhibition of locomotor activity when administered alone, while their combination displayed enhanced therapeutic effects. Isobolographic analysis revealed that combined butorphanol and dexmedetomidine produced synergistic interactions in the hot-plate, tail-immersion and locomotor activity tests. Furthermore, the analgesic synergy was also approved to be modulated by MORs, KORs, DORs and α₂ARs. Hence we concluded from this study that combined butorphanol and dexmedetomidine produced synergistic antinociception that may be helpful in facilitating clinical management of acute nociceptive pain.