Activation of C fibers by metabolic perturbations associated with tourniquet ischemia

Peripheral A-delta and C fibers are activated during the production of ischemic or tourniquet pain; however, individual metabolic or molecular factors responsible for neural activation are not known. To elucidate these mechanisms the in vitro corneal nerve preparation was used. Electrophysiologic effects of individual metabolic perturbations associated with ischemia (hypoxia, hypoglycemia, lactic acid, and decreased pH) were investigated on A-delta and C fiber nociceptors. Increased tonic action potential activity occurred in C fibers but not in A-delta fibers after ischemia. The conduction velocity of C fibers was 0.85 +/- 0.2 m/s (mean +/- SD). Under control conditions (n = 43) there was very little fluctuation in the baseline action potential frequency (+/- 3.2%). Hypoxia (n = 12) resulted in a 213 +/- 3.4% (mean +/- SD) increase in C fiber action potential frequency relative to control (P less than 0.001, ANOVA). L-glucose substitution for D-glucose (n = 8) increased C fiber discharge frequency by 653 +/- 28% relative to control (P less than 0.001) as did the combination of hypoxia and L-glucose substitution (n = 6) by 671 +/- 14%. Comparison of hypoxia versus hypoxia and hypoglycemia conditions did not show them to be statistically different (P greater than 0.5). Lactate (10-1000 micrograms/ml) at a pH of 6.9 or 7.4 did not alter the action potential discharge frequency in corneal C fibers (n = 5, P greater than 0.5).