• Andras Garami, Mohab Ibrahim, Kerry Gilbraith, Rajesh Khanna, Eszter Pakai, Alexandra Miko, Erika Pinter, Andrej A Romanovsky, Frank Porreca, and Amol M Patwardhan.
• From the Institute for Translational Medicine (A.G., E. Pakai, A.M.) and Department of Pharmacology and Pharmacotherapy (E. Pinter), Medical School, University of Pecs, Pecs, Hungary; Departments of Anesthesiology (M.I., K.G., F.P., A.M.P.), Pharmacology (M.I., K.G., R.K., F.P., A.M.P.), and Neuroscience (R.K.), University of Arizona, Tucson, Arizona; Systemic Inflammation Laboratory (FeverLab), Trauma Research, St. Joseph's Hospital and Medical Center, Phoenix, Arizona (A.A.R.).
• Anesthesiology. 2017 Nov 1; 127 (5): 813-823.

BackgroundIntraoperative hypothermia and postoperative pain control are two important clinical challenges in anesthesiology. Transient receptor potential vanilloid 1 has been implicated both in thermoregulation and pain. Transient receptor potential vanilloid 1 antagonists were not advanced as analgesics in humans in part due to a side effect of hyperthermia. This study tested the hypothesis that a single, preincision injection of a transient receptor potential vanilloid 1 antagonist could prevent anesthesia-induced hypothermia and decrease the opioid requirement for postsurgical hypersensitivity.MethodsGeneral anesthesia was induced in rats and mice with either isoflurane or ketamine, and animals were treated with transient receptor potential vanilloid 1 antagonists (AMG 517 or ABT-102). The core body temperature and oxygen consumption were monitored during anesthesia and the postanesthesia period. The effect of preincision AMG 517 on morphine-induced reversal of postincision hyperalgesia was evaluated in rats.ResultsAMG 517 and ABT-102 dose-dependently prevented general anesthesia-induced hypothermia (mean ± SD; from 1.5° ± 0.1°C to 0.1° ± 0.1°C decrease; P < 0.001) without causing hyperthermia in the postanesthesia phase. Isoflurane-induced hypothermia was prevented by AMG 517 in wild-type but not in transient receptor potential vanilloid 1 knockout mice (n = 7 to 11 per group). The prevention of anesthesia-induced hypothermia by AMG 517 involved activation of brown fat thermogenesis with a possible contribution from changes in vasomotor tone. A single preincision dose of AMG 517 decreased the morphine dose requirement for the reduction of postincision thermal (12.6 ± 3.0 vs. 15.6 ± 1.0 s) and mechanical (6.8 ± 3.0 vs. 9.5 ± 3.0 g) withdrawal latencies.ConclusionsThese studies demonstrate that transient receptor potential vanilloid 1 antagonists prevent anesthesia-induced hypothermia and decrease opioid dose requirements for the reduction of postincisional hypersensitivity in rodents.

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