Electrical stimulation at distinct peripheral sites in spinal nerve injured rats leads to different afferent activation profiles

Abstract

The neurophysiological basis by which neuromodulatory techniques lead to relief of neuropathic pain remains unclear. We investigated whether electrical stimulation at different peripheral sites induces unique profiles of A-fiber afferent activation in nerve-injured rats. At 4–6 weeks after subjecting rats to L5 spinal nerve injury (SNL) or sham operation, we recorded the orthodromic compound action potential (AP) at the ipsilateral L4 dorsal root in response to (1) transcutaneous electrical nerve stimulation (TENS, a patch electrode placed on the dorsum of the foot), (2) subcutaneous electrical stimulation (SQS, electrode inserted subcutaneously along the dorsum of the foot), (3) peroneal nerve stimulation (PNS, electrode placed longitudinally abutting the nerve), and (4) sciatic nerve stimulation (SNS). The area under the Aα/β compound AP was measured as a function of the bipolar, constant-current stimulus intensity (0.02–6.0 mA, 0.2 ms). In both nerve-injured and sham-operated groups, the stimulus-response (S-R) functions of the Aα/β compound APs differed substantially with the stimulation site; SNS having the lowest threshold and largest compound AP waveform, followed by PNS, SQS, and TENS. The S-R function to PNS was shifted to the right in the SNL group, compared to that in the sham-operated group. The Aα/β-threshold to PNS was higher in the SNL group than in the sham-operated group. The S-R functions and Aα/β-thresholds to TENS and SQS were comparable between the two groups. Electrical stimulation of different peripheral targets induced distinctive profiles of A-fiber afferent activation, suggesting that the neuronal substrates for the various forms of peripheral neuromodulatory therapies may differ.