Fig. 2 Neural discharge of A-HTMRs and perception of mechanical pain in response to punctate forces. Neural discharge of A-HTMRs and perception of mechanical.

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Fig. 2 Neural discharge of A-HTMRs and perception of mechanical pain in response to punctate forces. Neural discharge of A-HTMRs and perception of mechanical pain in response to punctate forces. (A) Peak discharge rates of human A-HTMRs for monofilament stimulation. The data show individual and average (±SEM) responses of nine A-HTMRs (≥30 m/s) to 5-s monofilament stimulation at eight different indentation forces. A significant linear fit was displayed (R2 = 0.6981, P = 0.0098), and the response at the highest indentation force (3000 mN) was significantly higher than responses to all weaker indentation forces (at least P < 0.05, Dunnett’s test). Individual units are color-coded. (B) Psychophysical data for pain intensity to graded monofilament stimulation. Psychophysical pain ratings were collected from 16 healthy participants (dorsal foot: 8 participants, 12 trial sets; dorsal toe: 8 participants, 9 trial sets) from the microneurography sample. The monofilament force had a significant effect on psychophysical pain ratings [F(8,171) = 29.96; P < 0.0001, two-way ANOVA], with a significant pain of ~14 of 100 emerging at 260 mN, and higher pain ratings with increasing forces (Tukey’s multiple comparisons test). No difference in pain ratings was found between the foot and toe stimulation sites [F(1,171) = 0.1733; P = 0.6777, two-way ANOVA]; hence, the data were pooled for a subsequent analysis. (C) Psychophysical pain ratings as a function of neural discharge in A-HTMRs. A comparison of the average peak discharge rates of nine A-HTMRs and average psychophysical pain ratings for skin indentations (eight forces, 4 to 3000 mN) revealed a significant positive correlation (Pearson r = 0.8944, R2 = 0.8, P = 0.0027). (D) Number of spikes produced by monofilament stimulation in human A-HTMRs. Individual and average (±SEM) responses of nine A-HTMRs to 5-s monofilament stimulation at eight different indentation forces. A significant linear fit was displayed (R2 = 0.6361, P = 0.0177). Individual units are color-coded. (E) Spike activity of an A-HTMR during the first 0.5 s of monofilament stimulation (with force feedback). Top: Neural discharge rates. Middle: Spike markers and indentation force markers. Bottom: Neural recording. The first 0.5 s was selected as the onset period (dynamic phase) of monofilament stimulation (total duration, 5 s). (F) Mean discharge rates of human A-HTMRs for monofilament onset. Individual and average (±SEM) responses of nine A-HTMRs to the onset period (0.5 s) of monofilament stimulation at eight different indentation forces. A significant linear fit was displayed (R2 = 0.6784, P = 0.0120). Individual units are color-coded. Saad S. Nagi et al. Sci Adv 2019;5:eaaw1297 Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).