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Neuroscience. 2018 Sep 1;387:4-12. doi: 10.1016/j.neuroscience.2018.03.006. Epub 2018 Mar 15.

Low-Frequency Stimulation of Silent Nociceptors Induces Secondary Mechanical Hyperalgesia in Human Skin.

Author information

1
Dept. Experimental Pain Research, CBTM, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Medical Faculty Mannheim, Heidelberg University, Germany; Dept. of Physiology & Experimental Pathophysiology, Universitaetsstr. 17, 91054 Erlangen, University of Erlangen, Nürnberg, Germany.
2
Dept. of Physiology & Experimental Pathophysiology, Universitaetsstr. 17, 91054 Erlangen, University of Erlangen, Nürnberg, Germany; Dept. Experimental Pain Research, CBTM, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Medical Faculty Mannheim, Heidelberg University, Germany.
3
Dept. of Clinical Neurophysiology, University Hospital Uppsala, S-75185 Uppsala, University of Uppsala, Sweden.
4
Dept. Experimental Pain Research, CBTM, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Medical Faculty Mannheim, Heidelberg University, Germany.
5
Dept. Experimental Pain Research, CBTM, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Medical Faculty Mannheim, Heidelberg University, Germany. Electronic address: martin.schmelz@medma.uni-heidelberg.de.

Abstract

Secondary mechanical hyperalgesia to punctate mechanical stimuli and light touch (allodynia) are prominent symptoms in neuropathic pain states. In a combined microneurographic and psychophysical study, we investigated the role of mechano-insensitive (silent) nociceptors regarding induction. Electrical thresholds of mechano-sensitive and silent nociceptors were assessed by microneurography with two closely spaced intracutaneous electrodes (i.c.) and a transcutaneous configuration (t.c.) in the foot dorsum. For t.c. stimulation there was a marked difference between silent (median, quartiles; 60, 50-70 mA, n = 63) and mechano-sensitive fibers (3, 2-5 mA, n = 107). In silent fibers, thresholds were lower for i.c. stimulation (16, 14-19 mA, n = 8), but higher in mechano-sensitive units (6, 5-6 mA, n = 13). Corresponding psychophysical tests showed no difference between the stimulation configuration for pain thresholds, but lower thresholds for the i.c. stimulation in axon reflex erythema (12 vs. 21 mA), punctate hyperalgesia (9 vs. 15 mA) and allodynia (15 vs. 18 mA). Punctate hyperalgesia was evoked at very low stimulation frequencies of 1/20 Hz (7/7 subjects), whereas the induction of an axon reflex flare required stimulation at 1/5 Hz. Electrical stimulation which is sufficient to excite mechano-insensitive C nociceptors can induce secondary mechanical hyperalgesia even at low frequencies supporting a role of such low-level input to clinical pain states. Thus, differential nociceptor class-specific input to the spinal cord adds to the complexity of modulatory mechanisms that determine nociceptive processing in the spinal cord.

KEYWORDS:

allodynia; flare; neurogenic inflammation; pain; punctate hyperalgesia; sensitization

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