Antinociceptive interaction between spinal clonidine and lidocaine in the rat formalin test: An isobolographic analysis

Clinical and basic science studies suggest that spinal alpha -2-adrenergic receptor agonists and local anesthetics produce analgesia, but interaction between alpha -2-adrenergic receptor agonists and local anesthetics in the persistent pain model has not been examined. In the present study, using is obolographic analysis, we investigated the antinociceptive interaction of i ntrathecal clonidine and lidocaine in the rat formalin test. Sprague-Dawley rats were implanted with chronic lumbar intrathecal catheters, and were te sted for paw flinch by formalin injection. Biphasic painful behavior was co unted. Intrathecal clonidine (3-12 nmol) was administered 15 min before for malin, and intrathecal lidocaine (375-1850 nmol) was administered 5 min bef ore formalin. To examine the interaction of intrathecal clonidine and lidoc aine, an isobolographic design was used. Spinal administration of clonidine produced dose-dependent suppression of the biphasic responses in the forma lin test. Spinal lidocaine resulted in dose-dependent transient motor dysfu nction and the motor dysfunction recovered to normal at 10-15 min after adm inistration. Spinal lidocaine produced dose-dependent suppression of phase- 2 activity in the formalin test. Isobolographic analysis showed that the co mbination of intrathecal clonidine and lidocaine synergistically reduced Ph ase-2 activity. We conclude that intrathecal clonidine synergistically inte racts with lidocaine in reducing the nociceptive response in the formalin t est.