Excitability changes in peripheral nerve fibers after repetitive electrical stimulation. Implications in pain modulation.

The Melzack-Wall gate control theory has been invoked to explain the peripheral analgesia resulting from repetitive electrical stimulation of peripheral nerve. This model emphasizes presynaptic inhibitory interactions among afferent fiber terminals in the spinal cord. An alternative explanation, that of velocity change in peripheral nerve fiber conduction, has been suggested by compound action potential studies from our laboratory. The present study was designed to extend this work, and to investigate the single fiber changes subsequent to brief (5- to 20-minute) periods of repetitive, high frequency (180 to 200/sec) electrical stimulation through an implantable peripheral nerve cuff device of the type used clinically for pain relief. Most fibers, regardless of their diameter (estimated from conduction velocity), show one or more of the following characteristics: a transient slowing of conduction velocity, an increase in electrical threshold and/or a decrease in response probability following a period of repetitive electrical stimulation. This supports the hypothesis that there are changes in direct peripheral nerve fiber excitability occurring under conditions simulating clinical electroanalgesia.

Direct effect of electrical stimulation on peripheral nerve evoked activity: implications in pain relief.

Experiments were performed with a peripheral neurostimulator, used clinically for pain relief, on isolated cat cutaneous peripheral nerve to determine the effect of electrical stimulation on components of the compound action potential. The results show that neurostimulation alters the conduction velocity and the amplitude of both the A-alpha and beta and the A-delta waves with the more slowly-conducting A-delta component showing the greatest changes. This direct alteration of peripheral nerve activity distal to the first synapse in the spinal cord might contribute to the mechanism of pain relief.

Repetitive electrical stimulation of peripheral nerve and spinal cord activity.

Spinal cord neuron and dorsal column fiber responses to electrical stimulation of the sciatic nerve in anesthetized cats were recorded before, during, and after periods of repetitive electrical stimulation of the sciatic nerve through an implantable nerve cuff stimulator device of the type and method used in human patients for pain relief. In previous publications from this laboratory using similar experimental conditions, we reported that repetitive electrical stimulation of the peripheral nerve suppressed all components of the compound action potential of nerves. The present study confirms that 5 percent of the spinal cord units studied showed facilitated discharge, 46 percent showed inhibited or depressed discharge, 36 percent underwent no change, and 13 percent showed equivocal responses to repetitive electrical stimulation. Inhibition of dorsal column fiber activity following repetitive electrical stimulation of peripheral nerve is not consistent with the Melzack-Wall gate hypothesis in which suppression of small fiber nociceptive input is mediated by large fiber activity. Our work suggests that the most commonly observed effect of electroanalgesia is to cause a more diffuse depression of nociceptive as well as nonnociceptive spinal cord activity.

Experimental cutaneous pain thresholds and tolerance in clinical analgesia with epidural morphine.

Ten patients experiencing significant analgesia from repeated low-dose morphine injections via an indwelling epidural catheter were studied. One group (n = 5) with acute, postoperative pain was tested for changes in experimental cutaneous pain thresholds with and without clinical morphine analgesia. Three of these patients received intravenous naloxone. The analgesia was reversed in two. There was no significant alteration in any cutaneous modality, including pain, although the postoperative deep pain was relieved. This discrepancy might be explained by the existence of separate subpopulations of opiate receptors at the spinal cord level, which differentiate nociceptive input from the skin and from deep body structures. The other group (n = 5) of cancer pain patients with a permanent epidural catheter was monitored for long-term changes in clinical pain. Signs of tolerance were not seen with an observation period up to 6 weeks.