Isobolographic analysis of interaction between spinal endomorphin-1, a newly isolated endogenous opioid peptide, and lidocaine in the rat formalin test

Endomorphin-1, a newly isolated endogenous opioid ligand,;has a potential a ffinity with mu-opioid receptor. We investigated antinociception of intrath ecal endomorphin-1 and lidocaine in the rat formalin test and examined the interaction between the two agents using isobolographic analysis. Intrathec al endomorphin-1 caused dose-dependent suppression of the formalin-induced biphasic behavioral response. Intrathecal lidocaine produced dose-dependent inhibition of phase-2 behavioral response. Isobolographic analysis confirm ed that combination of intrathecal endomorphin-1 and lidocaine, given at a fixed dose ratio, produced synergistic suppression of phase-2 behavioral re sponse. These data demonstrate that spinal endomorphin-1 synergistically in teracts with local anesthetic lidocaine in producing antinociception in the formalin test. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.