期刊
PAIN
卷 152, 期 5, 页码 1192-1200出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.pain.2011.01.051
关键词
ABT-102; TRPV1; Thermosensation; Heat pain threshold
资金
- Abbott [NCT: 00854659]
The capsaicin receptor (TRPV1) antagonist ABT-102 demonstrates efficacy in multiple preclinical pain models. However, evolving clinical data for this compound class suggest potentially profound drug-induced thermosensory impairment. Safety and tolerability of ABT-102 were assessed in a multiple-dose, double-blind, placebo-controlled, randomized healthy volunteer trial. Thirty-six participants were randomized in a 2: 1 ratio to ABT-102: placebo in 3 dose groups (1 mg, 2 mg, and 4 mg twice a day) and confined to an inpatient research unit for a 7-day treatment period and 3 follow-up days. Outcome measures included: oral and cutaneous cold detection, warm detection (WDT), and heat pain thresholds (HPT); oral perceived heat intensity (oral liquid test); time to hand withdrawal (water bath test); and cutaneous pain intensity (long thermal stimulus). Significant dose-dependent (placebo-and baseline-adjusted) increases in HPT and reduced painfulness of suprathreshold heat were present from days 1-7. For ABT-102 4 mg twice a day, model-based mean differences from placebo (95% confidence interval) were as follows: oral HPT, day 1 = 2.5 degrees C (0.6-4.4), day 5 = 4.4 degrees C (2.5-6.3); cutaneous HPT, day 2 = 3.3 degrees C (1.4-5.3), day 5 = 5.3 degrees C (3.3-7.2); oral WDT, day 1 = 2.6 degrees C (0.5-4.7), day 5 = 2.7 degrees C (0.6-4.9); cutaneous WDT, day 2 = 1.3 (0.0-2.6), day 5 = 1.6 (0.3-2.8) (all P < 0.05). Oral liquid test and water bath test results followed a similar pattern. There was no effect on cutaneous cold detection. All effects were fully reversed by day 10. There were no other relevant safety findings. Core body temperature remained below 39 degrees C in all participants. In conclusion, ABT-102 potently and reversibly increased HPT and reduced painfulness of suprathreshold oral/cutaneous heat. (C) 2011 Published by Elsevier B.V. on behalf of International Association for the Study of Pain.
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