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Vol. 282, Issue 2, 802-811, 1997
Pain Research Group, Department of Anesthesia Research
Laboratories, Harvard Medical School, Brigham and Women's
Hospital, 75 Francis Street, Boston, Massachusetts
Mechanosensitive A
-fibers (n = 29) and nociceptive
A
- (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
-, 0.1 to 0.6 mM for A
- 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
-fibers (IC50 = 0.41 ± 0.15 mM) and A
-fibers
(IC50 = 0.32 ± 0.18 mM). The [LID]
causing 50% impulse failure in A
-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
-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.
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