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

Andras Garami, Mohab Ibrahim, Kerry Gilbraith, Rajesh Khanna, Eszter Pakai, Alexandra Miko, E. Pintér, Andrej A. Romanovsky, Frank Porreca, Amol M. Patwardhan

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)813-823
Number of pages11
JournalAnesthesiology
Volume127
Issue number5
DOIs
Publication statusPublished - Nov 1 2017

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Induced Hypothermia
Opioid Analgesics
Rodentia
Anesthesia
Isoflurane
General Anesthesia
Morphine
Hypersensitivity
Fever
Brown Adipose Tissue
Anesthesiology
Thermogenesis
Body Temperature Regulation
Hyperalgesia
Ketamine
Postoperative Pain
Hypothermia
Body Temperature
Knockout Mice
Oxygen Consumption

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Transient Receptor Potential Vanilloid 1 Antagonists Prevent Anesthesia-induced Hypothermia and Decrease Postincisional Opioid Dose Requirements in Rodents. / Garami, Andras; Ibrahim, Mohab; Gilbraith, Kerry; Khanna, Rajesh; Pakai, Eszter; Miko, Alexandra; Pintér, E.; Romanovsky, Andrej A.; Porreca, Frank; Patwardhan, Amol M.

In: Anesthesiology, Vol. 127, No. 5, 01.11.2017, p. 813-823.

Research output: Contribution to journalArticle

Garami, A, Ibrahim, M, Gilbraith, K, Khanna, R, Pakai, E, Miko, A, Pintér, E, Romanovsky, AA, Porreca, F & Patwardhan, AM 2017, 'Transient Receptor Potential Vanilloid 1 Antagonists Prevent Anesthesia-induced Hypothermia and Decrease Postincisional Opioid Dose Requirements in Rodents', Anesthesiology, vol. 127, no. 5, pp. 813-823. https://doi.org/10.1097/ALN.0000000000001812
Garami, Andras ; Ibrahim, Mohab ; Gilbraith, Kerry ; Khanna, Rajesh ; Pakai, Eszter ; Miko, Alexandra ; Pintér, E. ; Romanovsky, Andrej A. ; Porreca, Frank ; Patwardhan, Amol M. / Transient Receptor Potential Vanilloid 1 Antagonists Prevent Anesthesia-induced Hypothermia and Decrease Postincisional Opioid Dose Requirements in Rodents. In: Anesthesiology. 2017 ; Vol. 127, No. 5. pp. 813-823.
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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.",
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AU - Gilbraith, Kerry

AU - Khanna, Rajesh

AU - Pakai, Eszter

AU - Miko, Alexandra

AU - Pintér, E.

AU - Romanovsky, Andrej A.

AU - Porreca, Frank

AU - Patwardhan, Amol M.

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