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Differential effect of Incobotulinumtoxin A on pain, neurogenic flare and hyperalgesia in human surrogate models of neurogenic pain

Diener, S.A., Breimhorst, M., Vogt, Th., Krämer, H.H., Drummond, P.D., Geber, C. and Birklein, F. (2017) Differential effect of Incobotulinumtoxin A on pain, neurogenic flare and hyperalgesia in human surrogate models of neurogenic pain. European Journal of Pain, 21 (8). pp. 1326-1335.

Link to Published Version: https://doi.org/10.1002/ejp.1031
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Abstract

Background: The effectiveness of Botulinum-neurotoxin A (BoNT/A) to treat pain in human pain models is very divergent. This study was conducted to clarify if the pain models or the route of BoNT/A application might be responsible for these divergent findings. Methods: Sixteen healthy subjects (8 males, mean age 27 ± 5 years) were included in a first set of experiments consisting of three visits: (1) Visit: Quantitative sensory testing (QST) was performed before and after intradermal capsaicin injection (CAPS, 15 μg) on one thigh and electrical current stimulation (ES, 1 Hz) on the contralateral thigh. During stimulation pain and the neurogenic flare response (laser-Doppler imaging) were assessed. (2) Four weeks later, BoNT/A (Xeomin®, 25 MU) was injected intracutaneously on both sides. (3) Seven days later, the area of BoNT/A application was determined by the iodine-starch staining and the procedure of the (1) visit was exactly repeated. In consequence of these results, 8 healthy subjects (4 males, mean age 26 ± 3 years) were included into a second set of experiments. The experimental setting was exactly the same with the exception that stimulation frequency of ES was increased to 4 Hz and BoNT/A was injected subcutaneously into the thigh, which was stimulated by capsaicin.

Results: BoNT/A reduced the 1 Hz ES flare size (p < 0.001) and pain ratings (p < 0.01), but had no effect on 4 Hz ES and capsaicin-induced pain, hyperalgesia, or flare size, regardless of the depth of BoNT/A injection (i.c./s.c). Moreover, i.c. BoNT/A injection significantly increased warm detection and heat pain thresholds in naive skin (WDT, Δ 2.2 °C, p < 0.001; HPT Δ 1.8 °C, p < 0.005).

Conclusion: BoNT/A has a moderate inhibitory effect on peptidergic and thermal C-fibers in healthy human skin.

Significance: The study demonstrates that BoNT/A (Incobotulinumtoxin A) has differential effects in human pain models: It reduces the neurogenic flare and had a moderate analgesic effects in low frequency but not high frequency current stimulation of cutaneous afferent fibers at C-fiber strength; BoNT/A had no effect in capsaicin-induced (CAPS) neurogenic flare or pain, or on hyperalgesia to mechanical or heat stimuli in both pain models. Intracutaneous BoNT/A increases warm and heat pain thresholds on naïve skin.

Publication Type: Journal Article
Murdoch Affiliation: School of Psychology and Exercise Science
Publisher: Blackwell Publishing Ltd
Copyright: © 2017 European Pain Federation - EFIC®
URI: http://researchrepository.murdoch.edu.au/id/eprint/38270
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