Botulinum toxin type A reduces histamine-induced itch and vasomotor responses in human skin

Abstract
Clinical evidence has revealed the antipruritic effect of botulinum toxin type A (BoNT/A). BoNT/A is believed to be effective against itch as it inhibits the release of acetylcholine as well as some other substances that may be involved in itch. To investigate the effect of subcutaneous administration of BoNT/A on experimentally histamine-induced itch in human skin. In this double-blind, placebo-controlled study, 14 healthy men (mean +/- SD age 26.3 +/- 2.6 years) received BoNT/A (Botox; Allergan, Irvine, CA, U.S.A.; 5 U) and isotonic saline on the volar surface of either forearm. Histamine prick tests were performed four times at the treatment sites (before treatment, and days 1, 3 and 7 after treatment). The itch intensity (as rated on a 0-10 visual analogue scale), itch area, neurogenic inflammation (visible flare area), blood flow (laser Doppler) and cutaneous temperature (thermographic images) were measured over the course of the trials. BoNT/A reduced the histamine-induced itch intensity (F(1,39) = 30.2, P < 0.001) and itch area (F(1,39) = 8.8, P = 0.011) compared with saline at all time points after treatment. The duration of itch was also shorter for BoNT/A-treated areas (F(1,39) = 19.4, P < 0.001), with a peak effect at day 7. The flare area was smaller in the BoNT/A-treated arm compared with the saline-treated arm at all time points after treatment (F(1,39) = 15.4, P = 0.002). Findings from blood flow (F(1,26) = 177.3, P < 0.001) and temperature measurements (F(1,26) = 27.6, P < 0.001) clearly showed the suppressive effect of BoNT/A on vasomotor reactions, with the maximal effect on days 3 and 7. BoNT/A reduced the itch intensity, blood flow and neurogenic inflammation in response to the histamine prick test in human skin. The findings could be applicable in the treatment of some pruritic conditions that can be difficult to treat with conventional treatments.