TY - JOUR
T1 - Physiological and pathological characterization of capsaicin-induced reversible nerve degeneration and hyperalgesia
AU - Chiang, H.
AU - Chang, K. C.
AU - Kan, H. W.
AU - Wu, S. W.
AU - Tseng, M. T.
AU - Hsueh, H. W.
AU - Lin, Y. H.
AU - Chao, C. C.
AU - Hsieh, S. T.
N1 - Funding Information:
This work was supported by National Science Council, Taiwan, and Ministry of Science and Technology, Taiwan (NSC 101-2314-B-002-163-MY3 and MOST 104-2314-B-002-046-MY3 to C-C.C., and MOST 104-2320-B-002-019-MY3 and MOST 105-2321-B-002-024 to S-T.H.).
Publisher Copyright:
© 2018 European Pain Federation - EFIC®
PY - 2018/7
Y1 - 2018/7
N2 - Background: The study aimed to investigate the physiology, psychophysics, pathology and their relationship in reversible nociceptive nerve degeneration, and the physiology of acute hyperalgesia. Methods: We enrolled 15 normal subjects to investigate intraepidermal nerve fibre (IENF) density, contact heat-evoked potential (CHEP) and thermal thresholds during the capsaicin-induced skin nerve degeneration–regeneration; and CHEP and thermal thresholds at capsaicin-induced acute hyperalgesia. Results: After 2-week capsaicin treatment, IENF density of skin was markedly reduced with reduced amplitude and prolonged latency of CHEP, and increased warm and heat pain thresholds. The time courses of skin nerve regeneration and reversal of physiology and psychophysics were different: IENF density was still lower at 10 weeks after capsaicin treatment than that at baseline, whereas CHEP amplitude and warm threshold became normalized within 3 weeks after capsaicin treatment. Although CHEP amplitude and IENF density were best correlated in a multiple linear regression model, a one-phase exponential association model showed better fit than a simple linear one, that is in the regeneration phase, the slope of the regression line between CHEP amplitude and IENF density was steeper in the subgroup with lower IENF densities than in the one with higher IENF densities. During capsaicin-induced hyperalgesia, recordable rate of CHEP to 43 °C heat stimulation was higher with enhanced CHEP amplitude and pain perception compared to baseline. Conclusions: There were differential restoration of IENF density, CHEP and thermal thresholds, and changed CHEP–IENF relationships during skin reinnervation. CHEP can be a physiological signature of acute hyperalgesia. Significance: These observations suggested the relationship between nociceptive nerve terminals and brain responses to thermal stimuli changed during different degree of skin denervation, and CHEP to low-intensity heat stimulus can reflect the physiology of hyperalgesia.
AB - Background: The study aimed to investigate the physiology, psychophysics, pathology and their relationship in reversible nociceptive nerve degeneration, and the physiology of acute hyperalgesia. Methods: We enrolled 15 normal subjects to investigate intraepidermal nerve fibre (IENF) density, contact heat-evoked potential (CHEP) and thermal thresholds during the capsaicin-induced skin nerve degeneration–regeneration; and CHEP and thermal thresholds at capsaicin-induced acute hyperalgesia. Results: After 2-week capsaicin treatment, IENF density of skin was markedly reduced with reduced amplitude and prolonged latency of CHEP, and increased warm and heat pain thresholds. The time courses of skin nerve regeneration and reversal of physiology and psychophysics were different: IENF density was still lower at 10 weeks after capsaicin treatment than that at baseline, whereas CHEP amplitude and warm threshold became normalized within 3 weeks after capsaicin treatment. Although CHEP amplitude and IENF density were best correlated in a multiple linear regression model, a one-phase exponential association model showed better fit than a simple linear one, that is in the regeneration phase, the slope of the regression line between CHEP amplitude and IENF density was steeper in the subgroup with lower IENF densities than in the one with higher IENF densities. During capsaicin-induced hyperalgesia, recordable rate of CHEP to 43 °C heat stimulation was higher with enhanced CHEP amplitude and pain perception compared to baseline. Conclusions: There were differential restoration of IENF density, CHEP and thermal thresholds, and changed CHEP–IENF relationships during skin reinnervation. CHEP can be a physiological signature of acute hyperalgesia. Significance: These observations suggested the relationship between nociceptive nerve terminals and brain responses to thermal stimuli changed during different degree of skin denervation, and CHEP to low-intensity heat stimulus can reflect the physiology of hyperalgesia.
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U2 - 10.1002/ejp.1189
DO - 10.1002/ejp.1189
M3 - Article
C2 - 29392825
AN - SCOPUS:85041184079
SN - 1090-3801
VL - 22
SP - 1043
EP - 1056
JO - European Journal of Pain (United Kingdom)
JF - European Journal of Pain (United Kingdom)
IS - 6
ER -