CHARACTERISTICS OF THE ANALGESIC EFFECTS AND DRUG-INTERACTIONS OF INTERACTIONS OF INTRATHECAL CARBACHOL IN RATS

Background: Intrathecal carbachol produces consistent analgesia in ani mals without appreciable adverse effects. Little is known about the ab ility of this drug to provide analgesia as stimulus intensity is incre ased. Likewise, there are few data regarding interactions between carb achol and other intrathecal analgesics. Methods: Using two different n oxious radiant heat intensities, one applied to each hind limb, analge sic effects of 1, 3, 10, and 30 mu g intrathecal carbachol on paw with drawal latencies were measured, Similar testing was done for intrathec al morphine and clonidine. ED(50) fractions (1/2, 1/4, 1/8, 1/16) of d rug combinations of carbachol-morphine and carbachol-clonidine were ad ministered, responses to the low intensity stimulus were recorded, and the ED(50) of each combination was established and isobolographic ana lysis of the drug interactions was carried out. Results: The 30-mu g d ose of carbachol was associated with transient agitation, salivation, and hind limb weakness. No other adverse effects were noted. The ED(50 ) (95% confidence interval) of intrathecal carbachol was 2.34 mu g (1. 34-4.04) for low intensity stimulation and 12.64 mu g (4.18-38.25) for high intensity. There was no significant difference between high- and low-intensity ED(50) values for intrathecal morphine and clonidine. T he analgesic effect of the carbachol-morphine and carbachol-clonidine combinations were significantly greater than the calculated additive e ffects. The ED(50) for the carbachol-morphine combination was 12% of t he expected additive value and the ED(50) for the carbachol-clonidine combination was 30% of the expected additive value. Conclusions: Intra thecal carbachol provides analgesia to noxious thermal stimulation of the hind paw in rats. It is relatively less effective at providing ana lgesia than intrathecal morphine or clonidine when stimulus intensity is raised. Intrathecal carbachol is synergistic when combined with int rathecal morphine or clonidine.