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

Gazerani, Parisa; Pedersen, Natalia Spicina; Staahl, Camilla; Drewes, Asbjørn Mohr; Arendt-Nielsen, Lars

doi:10.1016/j.pain.2008.10.005

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Volume 141, Issue 1 , Pages 60-69, January 2009

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

Parisa Gazerani
- Center for Sensory-Motor Interactions (SMI), Department of Health Sciences and Technology, Aalborg University, Fredrik Bajers Vej 7 D-3, DK-9220 Aalborg, Denmark
- Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada
Natalia Spicina Pedersen
- Center for Visceral Biomechanics and Pain, Department of Gastroenterology, Aalborg University Hospital, Denmark
Camilla Staahl
- Center for Sensory-Motor Interactions (SMI), Department of Health Sciences and Technology, Aalborg University, Fredrik Bajers Vej 7 D-3, DK-9220 Aalborg, Denmark
- Center for Visceral Biomechanics and Pain, Department of Gastroenterology, Aalborg University Hospital, Denmark
Asbjørn Mohr Drewes
- Center for Sensory-Motor Interactions (SMI), Department of Health Sciences and Technology, Aalborg University, Fredrik Bajers Vej 7 D-3, DK-9220 Aalborg, Denmark
- Center for Visceral Biomechanics and Pain, Department of Gastroenterology, Aalborg University Hospital, Denmark
Lars Arendt-Nielsen
- Center for Sensory-Motor Interactions (SMI), Department of Health Sciences and Technology, Aalborg University, Fredrik Bajers Vej 7 D-3, DK-9220 Aalborg, Denmark
- Corresponding author. Tel.: +45 9940 8830; fax: +45 9815 4008.

Received 4 March 2008; received in revised form 9 October 2008; accepted 14 October 2008. published online 12 November 2008.

Abstract

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 (22.5U) and isotonic saline in the mirror sides of their forehead. Pain and neurogenic inflammation was induced by four intradermal injections of capsaicin (100μg/μL) (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 Cfibers and probably TRPV1-receptors, block neurotransmitter release and subsequently reduce pain, neurogenic inflammation and cutaneous heat pain threshold.