Data previously presented at 13th World Congress on Pain, August 29–September 2, 2010, Montreal, Quebec, Canada
An oral TRPV1 antagonist attenuates laser radiant-heat-evoked potentials and pain ratings from UVB-inflamed and normal skin
Article first published online: 10 JAN 2013
© 2012 Abbott. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 75, Issue 2, pages 404–414, February 2013
How to Cite
Schaffler, K., Reeh, P., Duan, W. R., Best, A. E., Othman, A. A., Faltynek, C. R., Locke, C. and Nothaft, W. (2013), An oral TRPV1 antagonist attenuates laser radiant-heat-evoked potentials and pain ratings from UVB-inflamed and normal skin. British Journal of Clinical Pharmacology, 75: 404–414. doi: 10.1111/j.1365-2125.2012.04377.x
- Issue published online: 10 JAN 2013
- Article first published online: 10 JAN 2013
- Accepted manuscript online: 10 JUL 2012 05:44AM EST
- Manuscript Accepted: 25 JUN 2012
- Manuscript Received: 23 AUG 2011
- laser evoked potentials;
- phase 1;
- UV-inflamed skin;
- visual analogue scale
Laser (radiant-heat) evoked potentials (LEPs) from vertex-EEG peak-to-peak (PtP) amplitude were used to determine acute antinociceptive/antihyperalgesic efficacy of ABT-102, a novel TRPV1 antagonist efficacious in preclinical pain models, compared with active controls and placebo in normal and UVB-inflamed skin.
This was a randomized, placebo- and active-controlled, double-blind, intra-individual, crossover trial. Twenty-four healthy subjects received six sequences of single doses of ABT-102 (0.5, 2, 6 mg), etoricoxib 90 mg, tramadol 100 mg and placebo. Painful stimuli were induced by CO2-laser on normal and UVB-inflamed skin. LEPs and visual analogue scale (VAS-pain) ratings were taken at baseline and hourly up to 8 h post-dose from both skin types.
Compared with placebo, significant mean decreases in the primary variable of LEP PtP-amplitude from UVB-inflamed skin were observed with ABT-102 6 mg (P < 0.001), ABT-102 2 mg (P = 0.002), tramadol 100 mg (P < 0.001), and etoricoxib 90 mg (P = 0.001) over the 8 h period; ABT-102 0.5 mg was similar to placebo. ABT-102 6 mg was superior to active controls over the 8 h period (P < 0.05) whereas ABT-102 2 mg was comparable. Improvements in VAS scores compared with placebo were observed with ABT-102 6 mg (P < 0.001) and ABT-102 2 mg (P = 0.002). ABT-102 average plasma concentrations were 1.3, 4.4 and 9.4 ng ml−1 for the 0.5, 2 and 6 mg doses, respectively. There were no clinically significant safety findings.
TRPV-1 antagonism appears promising in the management of clinical pain, but requires further investigation.