Newly Published
Perioperative Medicine  |   August 2017
Transient Receptor Potential Vanilloid 1 Antagonists Prevent Anesthesia-induced Hypothermia and Decrease Postincisional Opioid Dose Requirements in Rodents
Author Notes
  • 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.).
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • A.G. and M.I. contributed equally to this article.
    A.G. and M.I. contributed equally to this article.×
  • Submitted for publication December 7, 2016. Accepted for publication July 11, 2017.
    Submitted for publication December 7, 2016. Accepted for publication July 11, 2017.×
  • Acknowledgments: The authors thank Jessica Hansen, B.S., Department of Pharmacology, University of Arizona, Tucson, Arizona, for her help conducting the experiments.
    Acknowledgments: The authors thank Jessica Hansen, B.S., Department of Pharmacology, University of Arizona, Tucson, Arizona, for her help conducting the experiments.×
  • Research Support: Supported by a Foundation for Anesthesia Education and Research grant (Schaumburg, Illinois; to Dr. Patwardhan), a University of Arizona Career Development grant (Tucson, Arizona; to Dr. Patwardhan), and in part by the Research Fund of the Medical School, University of Pecs (Pecs, Hungary; grant No. KA-2016-15) and the New National Excellence Program of the Hungarian Ministry of Human Capacities (Budapest, Hungary; UNKP-16-4-III).
    Research Support: Supported by a Foundation for Anesthesia Education and Research grant (Schaumburg, Illinois; to Dr. Patwardhan), a University of Arizona Career Development grant (Tucson, Arizona; to Dr. Patwardhan), and in part by the Research Fund of the Medical School, University of Pecs (Pecs, Hungary; grant No. KA-2016-15) and the New National Excellence Program of the Hungarian Ministry of Human Capacities (Budapest, Hungary; UNKP-16-4-III).×
  • Competing Interests: Drs. Patwardhan and Porreca declare a financial interest in Catalina Pharmaceuticals (Tucson, Arizona), which licenses the intellectual property involved in this research. Drs. Patwardhan, Porreca, and Romanovsky are founders of Catalina Pharma Inc. (Tucson, Arizona) and hold a provisional patent for the use of transient receptor potential vanilloid 1 antagonists in the prevention of anesthesia-induced hypothermia. Dr. Romanovsky has consulted for Abbott Laboratories (Chicago, Illinois), AbbVie (Chicago, Illinois), Amgen Inc. (Thousand Oaks, California), Japan Tobacco Inc. (Geneva, Switzerland), Teva Pharmaceutical Industries Ltd. (North Wales, Pennsylvania), and other pharmaceutical companies, and his research has been supported by Abbott Laboratories, AbbVie, and Amgen Inc. The other authors declare no competing interests.
    Competing Interests: Drs. Patwardhan and Porreca declare a financial interest in Catalina Pharmaceuticals (Tucson, Arizona), which licenses the intellectual property involved in this research. Drs. Patwardhan, Porreca, and Romanovsky are founders of Catalina Pharma Inc. (Tucson, Arizona) and hold a provisional patent for the use of transient receptor potential vanilloid 1 antagonists in the prevention of anesthesia-induced hypothermia. Dr. Romanovsky has consulted for Abbott Laboratories (Chicago, Illinois), AbbVie (Chicago, Illinois), Amgen Inc. (Thousand Oaks, California), Japan Tobacco Inc. (Geneva, Switzerland), Teva Pharmaceutical Industries Ltd. (North Wales, Pennsylvania), and other pharmaceutical companies, and his research has been supported by Abbott Laboratories, AbbVie, and Amgen Inc. The other authors declare no competing interests.×
  • Correspondence: Address correspondence to Dr. Patwardhan: Departments of Anesthesiology and Pharmacology, University of Arizona, 1501 North Campbell Avenue, Tucson, Arizona 85724. apatwardhan@anesth.arizona.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Pain Medicine / Patient Safety / Pharmacology
Perioperative Medicine   |   August 2017
Transient Receptor Potential Vanilloid 1 Antagonists Prevent Anesthesia-induced Hypothermia and Decrease Postincisional Opioid Dose Requirements in Rodents
Anesthesiology Newly Published on August 17, 2017. doi:10.1097/ALN.0000000000001812
Anesthesiology Newly Published on August 17, 2017. doi:10.1097/ALN.0000000000001812
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.