biostudies-literatureUnknown5(7)Nagi SSPain Relief FoundationALF Region ÖstergötlandDDIR Innovation AwardIntramural Research Program of the NIH, specifically the NCCIHNINDSSwedish Research Council FormasThe 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. TScience advanceseaaw1297https://www.ebi.ac.uk/biostudies/studies/S-EPMC6609212biostudies-literatureAn ultrafast system for signaling mechanical pain in human skin.PMC6609212Makdani AOlausson HRidderstrom MFoley ARTrulsson MShaikh SJarocka EO'Neill FSaade DBonnemann CGNagi SSCole JMcGlone FLiljencrantz JMinde JChesler ATMarshall AGDonkervoort SBushnell MCfalseAn ultrafast system for signaling mechanical pain in human skin.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. T2019-01-01T00:00:00Z2019 Jul2025-07-27T03:10:47.909Z2025-05-29T22:08:42.072ZS-EPMC66092123128188610.1126/sciadv.aaw1297