Experimental nerve block study on painful withdrawal reflex responses in humans

Abstract

The nociceptive withdrawal reflex (NWR) is a protective limb withdrawal response triggered by noxious stimuli, used to assess spinal nociceptive excitability. Conventionally, the NWR is understood as having two reflex responses: a quick (short-latency) response mediated by Aβ fibers, considered tactile, and a delayed (long-latency) response mediated by Aδ fibers, considered nociceptive. Yet, some studies challenge this distinction, suggesting a nociceptive component in the quick response. Further, high-threshold mechanoreceptors with conduction velocities similar to Aβ tactile afferents have been identified in human skin. In this study, we investigated the contribution of Aβ-fiber inputs to pain perception and NWR signaling using intradermal electrical stimulation before, during, and following recovery from a preferential Aβ-fiber ischemic block. We recorded a total of 198 NWR responses. No dual reflex responses occurred. The current intensity required to evoke the NWR was manifold higher than the perceptual pain threshold, indicating that NWR did not occur before pain was felt. During the preferential Aβ-fiber block, neither pain nor reflex could be evoked at the pre-block thresholds. Although delayed pain could be evoked at higher stimulus intensities, the reflex could not be evoked despite a two-fold increase in the pre-block current intensity and a five-fold increase in the pre-block pulse duration. Our findings underscore the importance of very fast-conducting cutaneous afferents in pain perception and NWR signaling during intradermal electrical stimulation. While pain perception involves multiple afferent classes, the absence of NWR during the block suggests an important contribution of cutaneous Aβ inputs in driving our nocifensive behaviors.