Differential nerve block. Direct measurements on individual myelinated and unmyelinated dorsal root axons.
BACKGROUND
Clinically, differential block is manifested by the loss of small fiber mediated sensation (e.g., temperature) two or more dermatomes beyond the sensory limit for large fiber mediated sensations. These observations support the belief that sensitivity to local anesthetics is inversely proportional to axon diameter. This study reports the first measurements of differential sensitivity to lidocaine in individual myelinated and unmyelinated mammalian dorsal root axons.


METHODS
Lumbar dorsal roots and vagus nerves were isolated from anesthetized adult rats and maintained in vitro in a perfusion/recording chamber at 37 +/- 0.3 degrees C. Using single fiber techniques, evoked action potentials in individual myelinated and unmyelinated axons were digitized and recorded for subsequent analysis. Axons were exposed to lidocaine at 150, 260, or 520 microM. Sensitivity to local anesthetic was assessed by measuring the incidence of conduction block and the magnitude of conduction velocity slowing under steady-state conditions.


RESULTS
Data were obtained from 77 dorsal root axons and 41 vagal axons. The estimated steady-state EC50 lidocaine concentration for myelinated dorsal root axons (232 microM) was comparable to that for unmyelinated axons (228 microM). Similarly, the incidence of conduction block was not significantly different among dorsal root axon groups. However, unmyelinated dorsal root axons were significantly less sensitive to the conduction velocity slowing effect of lidocaine than their myelinated counterparts (P < 0.01). The incidence of conduction block in short (mean length 13.5 mm) dorsal root axons was not significantly different from that in long (mean length 22.4 mm) axons. Compared with dorsal root axons, the estimated EC50s for vagal myelinated and unmyelinated axons (345 and 285 microM, respectively), while lower were not significantly different. However, the incidence of conduction block at 260 microM lidocaine was significantly lower (16.7% vs. 56.7%; P < 0.05) in vagal myelinated axons.


CONCLUSIONS
Although no difference in sensitivity to the conduction blocking effects of lidocaine could be demonstrated among dorsal root axons, myelinated axons were more sensitive to the conduction velocity slowing effects of lidocaine. This differential effect cannot explain clinical observations of differential nerve block. Differential sensory block with lidocaine may depend on factors (e.g., physiologic function) related only indirectly to individual axon conduction velocity (diameter).
Jaffe
R A
RA
Department of Anesthesia, Stanford University School of Medicine, California 94305-5115, USA. rajaffe@leland.stanford.edu
Rowe
M A
MA
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D009407:Nerve Block; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013126:Spinal Nerve Roots / Q000187:drug effects* / Q000502:physiology
D000779:Anesthetics, Local; D008012:Lidocaine