NEUROPHYSIOLOGIC ACTIONS AND NEUROLOGICAL CONSEQUENCES OF VERATRIDINEON THE RAT SCIATIC-NERVE

Background. The quest for a drug that would provide analgesia with min imal motor deficiency, through the selective inhibition of impulses in small-diameter fibers, was brightened by a previous report of veratri dine's C-fiber-selective actions on the isolated rabbit vagus nerve. T he goal of the present research was to demonstrate the same actions on rat sciatic nerve in vitro and to observe the functionally differenti al blockade in the rat in vivo. Methods: Sciatic nerves were removed f rom rats, mounted in a recording chamber, wherein a 1-cm length of the ensheathed nerve was superfused with the plant alkaloid veratridine ( 2 mu M) in bicarbonate-buffered Liley's solution, and the com pound ac tion potential (CAP) was stimulated supramaximally to give A- and C-fi ber elevations. Onset, steady-state, and recovery from veratridine eff ects were assayed for a range of stimulus frequencies. Open-field beha vior and quantitative neurological assessments of proprioception, moto r function, and nociception were tested in 15 trained rats after injec tion near the sciatic nerve of 0.1 ml veratridine at 0.5, 0.7, and 1.0 mM each plus epinephrine (1:200,000). Results: Veratridine inhibited the C-fiber component of the CAP in a frequency-dependent manner. At 0 .1 Hz the CAP was 65% of the control amplitude, 50% at 0.5 Hz, and 40% at 5 Hz. A-fiber elevations were unattenuated at stimulus frequencies as high as 50 Hz. Steady-state inhibition was reached 5 min after dru g administration, and recovery from the effects was 30% complete by 15 min of drug washout. Proprioception, measured as a ''hopping'' or ''p lacing'' reaction, was inhibited dose dependently by maximum degree an d for durations of, respectively, 0.5 mM, 61%, 180 min; 0.7 mM, 100%, 360 min; and 1 mM, 100%, 420 min. Extensor postural thrust, as a measu re of motor function, was inhibited by and for 0.5 mM, 77%, 240 min; 0 .7 mM, 99%, 390 min; and 1 mM, 100%, 420 min. Analgesia, as a prolonge d withdrawal latency to a noxious thermal stimulus, had the following profile: 0.5 mM, 10%, 30 min; 0.7 mM, 52%, 150 min; and 1 mM, 66%, 150 min. Conclusions: Despite the fact that veratridine gave a C-fiber pr eferential blockade in the isolated sciatic nerve, heightened analgesi a over motor block was not achieved in vivo. Indeed,just the opposite occurred If preferential C-fiber blockade also occurs in vivo, then it s traditionally expected correlation with analgesia must be reexamined .