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

Pain Rep. 2026 Jan 30;11(2):e1398. doi: 10.1097/PR9.0000000000001398. eCollection 2026 Apr.

ABSTRACT

INTRODUCTION: 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.

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

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

PMID:41635478 | PMC:PMC12863872 | DOI:10.1097/PR9.0000000000001398