An oral TRPV 1 antagonist attenuates laser radiant‐heat‐evoked potentials and pain ratings from UV B ‐inflamed and normal skin

• Published in: British journal of clinical pharmacology Vol. 75; no. 2; pp. 404 - 414
• Main Authors: Schaffler, Klaus, Reeh, Peter, Duan, W. Rachel, Best, Andrea E., Othman, Ahmed A., Faltynek, Connie R., Locke, Charles, Nothaft, Wolfram
• Format: Journal Article
• Language: English
• Published: 01.02.2013
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/j.1365-2125.2012.04377.x

Aims Laser (radiant‐heat) evoked potentials ( LEP s) from vertex‐ EEG p eak‐to‐ p eak ( PtP ) amplitude were used to determine acute antinociceptive/antihyperalgesic efficacy of ABT ‐102, a novel TRPV 1 antagonist efficacious in preclinical pain models, compared with active controls and placebo in normal and UV B ‐inflamed skin. Methods 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 CO 2 ‐laser on normal and UV B ‐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. Results Compared with placebo, significant mean decreases in the primary variable of LEP PtP ‐amplitude from UV B ‐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. Conclusions TRPV ‐1 antagonism appears promising in the management of clinical pain, but requires further investigation.