An oral TRPV1 antagonist attenuates laser radiant‐heat‐evoked potentials and pain ratings from UV_B‐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 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 CO₂‐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.

DOI: 10.1111/j.1365-2125.2012.04377.x

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