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Anesthesiology. 2017 Nov;127(5):813-823. doi: 10.1097/ALN.0000000000001812.

Transient Receptor Potential Vanilloid 1 Antagonists Prevent Anesthesia-induced Hypothermia and Decrease Postincisional Opioid Dose Requirements in Rodents.

Author information

1
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.).

Abstract

BACKGROUND:

Intraoperative 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.

METHODS:

General 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.

RESULTS:

AMG 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.

CONCLUSIONS:

These 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.

PMID:
28806222
DOI:
10.1097/ALN.0000000000001812
[Indexed for MEDLINE]

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