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Susceptibility to Lidocaine of Impulses in Different Somatosensory Afferent Fibers of Rat Sciatic Nerve

1997; American Society for Pharmacology and Experimental Therapeutics; Volume: 282; Issue: 2 Linguagem: Inglês

10.1016/s0022-3565(24)36879-x

1521-0103

Jason H. Huang, Johann G. Thalhammer, Stephen A. Raymond, Gary R. Strichartz,

Botulinum Toxin and Related Neurological Disorders

Mechanosensitive A beta-fibers (n = 29) and nociceptive A delta- (n = 6) and C-fibers (n = 10) of the rat sciatic nerve were superfused with lidocaine (LID, 0.1-1.4 mM) in vivo. The [LID] to abolish single electrically stimulated impulses (tonic blockade) in axons was 0.2 to 0.8 mM for A beta-, 0.1 to 0.6 mM for A delta- and 0.1 to 1.4 mM for C-fibers. Within each of the fiber groups there was no dependence of blocking [LID] on conduction velocity; slower fibers were no more susceptible than faster ones. Mean blocking concentrations differed between groups, with C-fibers having an IC50 = 0.80 +/- 0.32 mM (+/- S.E.), significantly higher (P < .05, ANOVA) than A beta-fibers (IC50 = 0.41 +/- 0.15 mM) and A delta-fibers (IC50 = 0.32 +/- 0.18 mM). The [LID] causing 50% impulse failure in A beta-fibers during a 200-Hz, 10-stimulus train (phasic blockade) ranged from 0.2 mM to 0.7 mM; the mean IC50 equaled 0.28 mM (n = 17). Stimulation of nociceptive A delta-fibers (n = 4) and C-fibers (n = 5) at 5 or 10 Hz for 10 pulses produced no phasic block at [LID]s (0.1-0.5 mM) below those required for tonic blockade. Uptake of 14C-lidocaine by the nerve, measured in vivo under conditions identical with those for electrophysiology, showed that: a) little drug was in the segments of nerve beyond the superfusion chamber, b) lidocaine was uniformly distributed in the nerve within the chamber, c) the intraneural lidocaine content was identical with that in nerves equilibrated in vitro. The results show a lack of monotonic dependence of sensitivity to local anesthetic on fiber diameter, but do suggest that mean susceptibility to nerve block by lidocaine differs for fibers grouped by, and perhaps according to, function.