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Microneurography was used in healthy human subjects to record action potentials from unmyelinated nerve fibers (C units) in cutaneous fascicles of the peroneal nerve. Activity-dependent slowing (n = 96) and transcutaneous electrical thresholds (n = 67) were determined. Eight units were sympathetic efferents according to their responses to sympathetic reflex provocations. Mechano-heat-responsive C units (CMH) (n = 56) had thresholds to von Frey hair stimulation ≤90 mN (6.5 bar). Mechano-insensitive C units (n = 32) were unresponsive to 750 mN (18 bar). Twenty-six mechano-insensitive units responded to heat (CH), and the remaining six units did not respond to physical stimuli but were proven to be afferent by their response to intracutaneous capsaicin (CMiHi). Mechano-insensitive units had significantly slower conduction velocity (0.81 ± 0.03 m/sec), and CH units had higher heat thresholds (48.0 ± 0.6°C) compared with CMH units (1.01 ± 0.01 m/sec; 40.7 ± 0.4°C). Transcutaneous electrical thresholds were <9 mA for CMH units and >35 mA for CH and CMiHi units. Activity-dependent slowing was much more pronounced in mechano-insensitive than in mechano-responsive units, without overlap. Sympathetic efferent C units showed intermediate slowing, significantly different from CMH, and completely separate from CH and CMiHi units. The activity-dependent slowing of conduction provides evidence for different membrane attributes of different classes of C fibers in humans.

Functional Attributes Discriminating Mechano-Insensitive and Mechano-Responsive C Nociceptors in Human Skin