The effects of Botulinum Toxin type A on capsaicin-evoked pain, flare, and secondary hyperalgesia in an experimental human model of trigeminal sensitization

The trigeminovascular system is involved in migraine. Efficacy of Botulinum Toxin type A (BoNT-A) in migraine has beef) investigated in clinical studies but the mechanism of action remains unexplored. It is hypothesized that BoNT-A inhibits peripheral sensitization of nociceptive fibers and indirectly reduces central sensitization. We examined the effect of intramuscular injection of BoNT-A on an experimental human model of trigeminal sensitization induced by intradermal capsaicin injection to the forehead. BoNT-A (BOTOX (R)) or saline was injected intramuscularly in precranial. neck and shoulder muscles to 32 healthy male volunteers in a double blind-randomized manner. Intradermally capsaicin-induced pain. flare and secondary hyperalgesia were obtained before and 1, 4 and 8 weeks after the above treatments. A significant suppressive effect of BoNT-A on pain, flare and hyperalgesia area was observed. The pain intensity area was significantly smaller in BoNT-A group (9.16 +/- 0.83 cm x s) compared to saline group (15.41 +/- 0.83 cm x s) (P = 0.011). The flare area was also reduced significantly in BoNT-A group (29.81 +/- 0.69 cm(2)) compared to saline group (39.71 +/- 0.69 cm(2)) (p < 0.001). Similarly, the mean area of secondary hyperalgesia was significantly Smaller in BoNT-A group (4.25 +/- 0.91 cm(2)) compared to saline group (7.03 +/- 0.91 cm(2)) (P = 0.040). Post hoc analysis showed significant differences across the trials with a remarkable suppression effect of BoNT-A off capsaicin-induced sensory and vasomotor reactions as early as week 1 (P < 0.001). BoNT-A presented suppressive effects on the trigeminal/cervical nociceptive system activated by intradermal injection of capsaicin to the forehead. The effects are suggested to be caused by a local peripheral effect of BoNT-A on cutaneous nociceptors. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.