Analgesia by low-frequency nerve stimulation mediated by low-threshold afferents in rats

Several authors claim that analgesia by low-frequency peripheral nerve stimulation (transcutaneously or through inserted needles) depends on the activation of small-diameter A delta afferents. In the present study, a marked increase in pain threshold assessed by the squeak threshold test (vocalization to electric shocks delivered to the tail) was obtained by 2 Hz sciatic or radial nerve low-intensity stimulation, using single pulses. Conduction velocities of the activated nerve fibers ranged between 33.6 and 46.4 m/sec, which is consistent with activation of large afferent A fibers. This analgesic effect was reversed by naloxone (3 mg/kg i.v.). Thus, low-threshold afferents may contribute to the analgesic effect in addition to the previously reported high-threshold induced effect. High-intensity stimulation (5-6 times the threshold for visible muscular twitches), activating small-diameter afferents (A delta fibers) resulted in a decrease in pain threshold. Hyperalgesia also resulted from low-intensity stimulation using trains of pulses. The analgesic or hyperalgesic effects were correlated with the animal's behavior during stimulation. Analgesia was obtained in calm rats, who went to sleep regularly. When the rats showed signs of being distressed, hyperalgesia resulted. These findings may explain the occasional failure to obtain reduction in pain in anxious human patients by peripheral stimulation.