Comparison of nalbuphine and naloxone for local cutaneous nociceptive blockade in rats

This study investigated the local inhibition of a reflexive cutaneous nociceptive response produced by nalbuphine and naloxone after subcutaneous administration and compared their pharmacological profiles with those of lidocaine. At the single equimolar dose tested (39.3 μmol/kg), nalbuphine produced significantly greater local cutaneous nociceptive blockade than naloxone. Dose-response analyses were subsequently performed for nalbuphine and lidocaine. Both nalbuphine and lidocaine produced dose-dependent local cutaneous nociceptive blockade, and no significant difference in ED 50 (50% effective dose) values was observed between the two drugs. Nalbuphine (65.5 μmol/kg) and lidocaine (52.4 μmol/kg) achieved complete cutaneous trunci muscle reflex (CTMR) blockade (100% of the maximal possible effect), with no statistically significant differences observed in complete block time, full recovery time, or area under the curve. Isobolographic analysis demonstrated that the experimentally derived ED 50 did not differ significantly from the theoretical additive ED 50 , indicating no evidence of departure from additivity under the conditions tested. Time-course analysis further confirmed no significant differences in the magnitude or duration of CTMR blockade between single drugs and their combination. These findings indicated that, at the single equimolar dose tested, nalbuphine produced greater local cutaneous nociceptive blockade than naloxone. No statistically significant difference in ED 50 values was observed between nalbuphine and lidocaine, and the interaction between nalbuphine and lidocaine was consistent with additivity.