An oral TRPV1 antagonist attenuates laser radiant‐heat‐evoked potentials and pain ratings from UVB‐inflamed and normal skin

Aims 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. 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 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. Results 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. Conclusions TRPV‐1 antagonism appears promising in the management of clinical pain, but requires further investigation.