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

Background The effectiveness of Botulinum‐neurotoxin A (Bo NT /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 Bo NT /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, Bo NT /A (Xeomin ® , 25  MU ) was injected intracutaneously on both sides. (3) Seven days later, the area of Bo NT /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 Bo NT /A was injected subcutaneously into the thigh, which was stimulated by capsaicin. Results Bo NT /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 Bo NT /A injection (i.c./s.c). Moreover, i.c. Bo NT /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 Bo NT /A has a moderate inhibitory effect on peptidergic and thermal C‐fibers in healthy human skin. Significance The study demonstrates that Bo NT /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; Bo NT /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 Bo NT /A increases warm and heat pain thresholds on naïve skin.