Subcutaneous Botulinum toxin type A reduces capsaicin-induced trigeminal pain and vasomotor reactions in human skin

The present human study aimed at investigating the effect of subcutaneous administration of Botulinum toxin type A (BoNT/A) on capsaicin-induced trigeminal pain, neurogenic inflammation and experimentally induced cutaneous pain modalities. Fourteen healthy males (26.3 +/- 2.6 years) were included in this double-blind and placebo-controlled trial. The subjects received subcutaneous BoNT/A (22.5 U) and isotonic saline in the mirror sides of their forehead. Pain and neurogenic inflammation was induced by four intradermal injections of capsaicin (100 mu g/mu L) (before, and days 1, 3 and 7 after treatments). The capsaicin-induced pain intensity, pain area, the area of secondary hyperalgesia, the area of visible flare and vasomotor reactions were recorded together with cutaneous heat, electrical and pressure pain thresholds. BoNT/A reduced the capsaicin-induced trigeminal pain intensity compared to saline (F=37.9, P<0.001). The perceived pain area was smaller for the BoNT/A-treated side compared to saline (F= 7.8. P < 0.05). BoNT/A reduced the capsaicin-induced secondary hyperalgesia (F= 5.3, P < 0.05) and flare area (F= 10.3, P < 0.01) compared to saline. BoNT/A reduced blood flow (F-1.26 = 109.5, P < 0.001) and skin temperature (F-1.26 = 63.1, P < 0.001) at the capsaicin injection sites compared to saline and its suppressive effect was maximal at days 3 and 7 (P < 0.05, post hoc test). BoNT/A elevated cutaneous heat pain thresholds (F = 17.1. P < 0.001) compared to saline; however, no alteration was recorded for electrical or pressure pain thresholds (P > 0.05). Findings from the present study suggest that BoNT/A appears to preferentially target Clibers and probably TRPV1-receptors, block neurotransmitter release and subsequently reduce pain, neurogenic inflammation and cutaneous heat pain threshold. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.