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Investigation of the predictive validity of laser‐EPs in normal, UVB‐inflamed and capsaicin‐irritated skin with four analgesic compounds in healthy volunteers
Author(s) -
Schaffler Klaus,
Nicolas Laurent B.,
Borta Andreas,
Brand Tobias,
Reitmeir Peter,
Roebling Robert,
Scholpp Joachim
Publication year - 2017
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13247
Subject(s) - pregabalin , lacosamide , duloxetine , placebo , medicine , anesthesia , celecoxib , visual analogue scale , analgesic , nociception , duloxetine hydrochloride , crossover study , pharmacology , epilepsy , alternative medicine , receptor , pathology , psychiatry
Aims The aim of the present study was to assess the predictivity of laser‐(radiant‐heat)‐evoked potentials (LEPs) from the vertex electroencephalogram, using an algesimetric procedure, testing the anti‐nociceptive/anti‐hyperalgesic effects of single oral doses of four marketed analgesics (of different compound classes) vs. placebo, in healthy volunteers with three skin types. Methods This was a randomized, placebo‐controlled, single‐blind, five‐way‐crossover trial. Twenty‐five healthy male/female Caucasians were included (receiving celecoxib 200 mg, pregabalin 150 mg, duloxetine 60 mg, lacosamide 100 mg or placebo) in a Williams design, with CO 2 laser‐induced painful stimuli to normal, ultraviolet (UV) B‐inflamed and capsaicin‐irritated skin. LEPs and visual analogue scale ratings were taken at baseline and hourly for 6 h postdose from all three skin types. Results In normal skin, the averaged postdose LEP peak‐to‐peak‐(PtP)‐amplitudes were reduced by pregabalin (−2.68 μV; 95% confidence interval (CI) −4.16, 1.19) and duloxetine (−1.73 μV; 95% CI −3.21, −0.26) but not by lacosamide and celecoxib vs. placebo. On UVB‐irradiated skin, reflecting inflammatory pain, celecoxib induced a pronounced reduction in LEP PtP amplitudes vs. placebo (−6.2 μV; 95% CI −7.88, −4.51), with a smaller reduction by duloxetine (−4.54 μV; 95% CI −6.21, −2.87) and pregabalin (−3.72 μV; 95% CI −5.40, −2.04), whereas lacosamide was inactive. LEP PtP amplitudes on capsaicin‐irritated skin, reflecting peripheral/spinal sensitization, as in neuropathic pain, were reduced by pregabalin (−3.78 μV; 95% CI −5.31, −2.25) and duloxetine (−2.32 μV; 95% CI −3.82, −0.82) but not by celecoxib or lacosamide vs. placebo, which was in agreement with known clinical profiles. Overall, PtP amplitude reductions were in agreement with subjective ratings. Conclusions LEP algesimetry is sensitive to analgesics with different modes of action and may enable the effects of novel analgesics to be assessed during early clinical development.