An ultrafast system for signaling mechanical pain in human skin

Abstract

The canonical view is that touch is signaled by fast-conducting, thickly myelinated afferents, whereas pain is signaled by slow-conducting, thinly myelinated (“fast” pain) or unmyelinated (“slow” pain) afferents. While other mammals have thickly myelinated afferents signaling pain (ultrafast nociceptors), these have not been demonstrated in humans. Here, we performed single-unit axonal recordings (microneurography) from cutaneous mechanoreceptive afferents in healthy participants. We identified A-fiber high-threshold mechanoreceptors (A-HTMRs) that were insensitive to gentle touch, encoded noxious skin indentations, and displayed conduction velocities similar to A-fiber low-threshold mechanoreceptors. Intraneural electrical stimulation of single ultrafast A-HTMRs evoked painful percepts. Testing in patients with selective deafferentation revealed impaired pain judgments to graded mechanical stimuli only when thickly myelinated fibers were absent. This function was preserved in patients with a loss-of-function mutation in mechanotransduction channel PIEZO2. These findings demonstrate that human mechanical pain does not require PIEZO2 and can be signaled by fast-conducting, thickly myelinated afferents.

High prevalence of carpal tunnel syndrome in individuals with rare nerve growth factor-beta mutation

“…Several of these had foot deformities including Charcot joints. In a recent study, we screened for thermal function and found two patients in this cohort who had no cold (<20°C) or heat pain (>50°C) perception and yet their mechanical pain perception was intact, a feature that from convergent evidence is likely signalled by the large-diameter (A-beta) nociceptors ( Nagi et al , 2019 ).…”

Tapping Into the Language of Touch: Using Non-invasive Stimulation to Specify Tactile Afferent Firing Patterns

“…This enables computational processing of the sensor signals to optimise the sensory experience by stimulating each afferent with input from appropriate sensors in appropriate patterns. For some afferents, this mapping should prove straight-forward, as it seems that in general single FAI and FAII afferents can give rise to a clear and localised percept (Ochoa and Torebjörk, 1983;Vallbo and Johansson, 1984) and SAI from the dorsum of the foot and hand can evoke conscious sensation (Nagi et al, 2019). In contrast, single SAII afferents (Ochoa and Torebjörk, 1983), and SAI afferents from the hairy skin of the forearm (Vickery et al, 1993), do not appear to give rise to a conscious percept.…”

Pain, Touch, and Decision Making : Behavioral and Brain Responses to Affective Somatosensory Stimulation

“…C fibers are small, unmyelinated, and have slow conduction velocity. In humans, Ab afferents are thought to mainly signal discriminative aspects of touch (although a small fraction of them transmit pain, see Nagi et al, 2019), whereas Ad fibers signal pain and C fibers signal pain and affective aspects of touch.…”