ANTINOCICEPTIVE INTERACTION OF INTRATHECAL ALPHA(2)-ADRENERGIC AGONISTS, TIZANIDINE AND CLONIDINE, WITH LIDOCAINE IN RATS

Background: The intrathecal alpha(2)-adrenergic agonist, clonidine, ha s been shown to have considerable antinociceptive effect, although clo nidine causes hypotension and bradycadia. The combination of intrathec al clonidine and local anesthetics enhances analgesic effects, whereas the combination may cause marked hypotension and motor blockade, whic h may limit the clinical application of the combination. Tizanidine, a nother alpha(2)-adrenergic agonist, has also provided antinociception without producing pronounced hemodynamic changes, This study was desig ned to evaluate the antinociceptive and hemodynamic interactions of ti zanidine and clonidine with lidocaine. Methods: Male Sprague Dawley ra ts were chronically implanted with lumbar intrathecal catheters. The t ail-flick test was used to assess the thermal nociceptive threshold. T he ability of intrathecal tizanidine, clonidine, Lidocaine, or the com binations of alpha(2)-adrenergic agonist and lidocaine to alter the ta il-flick latency was examined. To characterize;he antinociceptive inte raction, the isobolographic analysis was applied, Additionally , the m otor function, blood pressure and heart rate after intrathecal adminis tration of drugs and combinations were also monitored. Results: intrat hecal tizanidine, clonidine, or the combinations increased the tail-fl ick latency in dose-and time-dependent fashion without affecting motor function. The order potencies (dose producing a 50% of peak effect, i n mu g) of tizanidine and clonidine were 1.8 and 0.75, respectively, W ith isobolographic analysis, tizanidine with Lidocaine and clonidine w ith lidocaine showed significantly synergistic antinociceptive interac tion. Potency ratio analysis and fractional analysis also confirmed th e synergistic interaction, At the doses in the combinations showing co mparable antinociception, tizanidine with Lidocaine, unlike clonidine with lidocaine, did not affect motor function or blood pressure. Concl usion: The authors' results show that intrathecal tizanidine and cloni dine synergistically interact with lidocaine so that the degree of ant inociception to somatic noxious stimuli are enhanced, The antinocicept ive synergistic interaction between tizanidine and lidocaine may be us eful in clinical practice without affecting blood pressure, heart rate , or motor function.