Coding of mechanical pain by myelinated and unmyelinated nociceptors in human hairy skin

In humans, cutaneous Aβ afferents are traditionally linked to discriminative touch, while pain is attributed to Aδ and C fibers. However, we previously identified thickly myelinated high-threshold mechanoreceptors (Aβ-HTMRs) that encode noxious skin indentations and evoke painful percepts when selectively activated. These afferents also display finely grained receptive fields and resilience to fatigue during sustained stimulation.

To characterize the tuning properties of A-HTMRs under controlled mechanical stimulation and compare them with C-HTMRs.

We used a robotic stimulation system capable of delivering precise skin indentations across a wide force range (20-1000 mN). Single-unit axonal recordings (microneurography) were obtained from cutaneous afferents of the radial nerve in awake healthy participants. Both low- and high-threshold mechanoreceptors were recorded.

Among 39 recorded mechanoreceptive afferents, HTMRs were distinguished by high mechanical thresholds and lack of response to soft brushing, with conduction velocities in the Aβ- and C-fiber ranges. Both A- and C-HTMRs exhibited force-dependent increases in spike count and firing rate, with A-HTMRs showing significantly stronger responses. Principal component analysis revealed distinct separation between A- and C-HTMRs, driven by A-HTMRs' robust high-force responses. Psychophysical testing indicated painful stimuli were often described as "sharp," and selective intraneural microstimulation of a single A-HTMR evoked localized "sharp-stinging" pain projected to its receptive field.

Robot-controlled stimulation confirmed both A- and C-HTMRs' role in encoding painful mechanical stimuli. The fast conduction, high firing rates, fine receptive fields, and fatigue resilience of A-HTMRs suggest a specialized nociceptive system capable of conveying rich spatial-temporal information, potentially contributing to protective behaviors.