Newly Published
Perioperative Medicine  |   June 2017
A Subregion of the Parabrachial Nucleus Partially Mediates Respiratory Rate Depression from Intravenous Remifentanil in Young and Adult Rabbits
Author Notes
  • From the Department of Biology, Carthage College, Kenosha, Wisconsin (J.R.M.); Departments of Anesthesiology (J.R.M., E.J.Z., E.A.E.S., A.G.S.) and Biostatistics (A.B.), Medical College of Wisconsin, Milwaukee, Wisconsin; Children’s Hospital of Wisconsin, Milwaukee, Wisconsin (E.A.E.S., A.G.S.); and Zablocki VA Medical Center, Milwaukee, Wisconsin (E.J.Z., F.A.H.).
  • Submitted for publication August 30, 2016. Accepted for publication May 1, 2017.
    Submitted for publication August 30, 2016. Accepted for publication May 1, 2017.×
  • Acknowledgments: The authors thank Jack Tomlinson (biological laboratory technician) and Jennifer Callison, B.S., of the Medical College of Wisconsin, Milwaukee, Wisconsin, for excellent technical assistance.
    Acknowledgments: The authors thank Jack Tomlinson (biological laboratory technician) and Jennifer Callison, B.S., of the Medical College of Wisconsin, Milwaukee, Wisconsin, for excellent technical assistance.×
  • Research Support: Support was provided by the Foundation for Anesthesia Education and Research, Schaumburg, Illinois (FAERMRTG-BS-02-15-2010 to Dr. Stucke), the National Institutes of Health, Bethesda, Maryland (R01GM112960-02 to Dr. Stucke), and the Department of Veterans Affairs, Washington, DC (VA Merit Review Biomedical Laboratory Research and Development Award No. 2 I01 BX000721-05 to Dr. Zuperku). This publication was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, through grant No. UL1TR001436.
    Research Support: Support was provided by the Foundation for Anesthesia Education and Research, Schaumburg, Illinois (FAERMRTG-BS-02-15-2010 to Dr. Stucke), the National Institutes of Health, Bethesda, Maryland (R01GM112960-02 to Dr. Stucke), and the Department of Veterans Affairs, Washington, DC (VA Merit Review Biomedical Laboratory Research and Development Award No. 2 I01 BX000721-05 to Dr. Zuperku). This publication was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, through grant No. UL1TR001436.×
  • Competing Interests: The authors declare no competing interests.
    Competing Interests: The authors declare no competing interests.×
  • Correspondence: Address correspondence to Dr. Stucke: Department of Anesthesiology, Medical College of Wisconsin, 8700 W. Watertown Plank Road, Milwaukee, Wisconsin 53201. astucke@mcw.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 / Central and Peripheral Nervous Systems / Pain Medicine / Pharmacology
Perioperative Medicine   |   June 2017
A Subregion of the Parabrachial Nucleus Partially Mediates Respiratory Rate Depression from Intravenous Remifentanil in Young and Adult Rabbits
Anesthesiology Newly Published on June 8, 2017. doi:10.1097/ALN.0000000000001719
Anesthesiology Newly Published on June 8, 2017. doi:10.1097/ALN.0000000000001719
Abstract

Background: The efficacy of opioid administration to reduce postoperative pain is limited by respiratory depression. We investigated whether clinically relevant opioid concentrations altered the respiratory pattern in the parabrachial nucleus, a pontine region contributing to respiratory pattern generation, and compared these effects with a medullary respiratory site, the pre-Bötzinger complex.

Methods: Studies were performed in 40 young and 55 adult artificially ventilated, decerebrate rabbits. We identified an area in the parabrachial nucleus where α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid microinjections elicited tachypnea. Two protocols were performed in separate sets of animals. First, bilateral microinjections of the μ-opioid receptor agonist [D-Ala,2 N-MePhe,4 Gly-ol]-enkephalin (100 μM) into the “tachypneic area” determined the effect of maximal μ-opioid receptor activation. Second, respiratory rate was decreased with continuous IV infusions of remifentanil. The opioid antagonist naloxone (1 mM) was then microinjected bilaterally into the “tachypneic area” of the parabrachial nucleus to determine whether the respiratory rate depression could be locally reversed.

Results: Average respiratory rate was 27 ± 10 breaths/min. First, [D-Ala,2 N-MePhe,4 Gly-ol]-enkephalin injections decreased respiratory rate by 62 ± 20% in young and 45 ± 26% in adult rabbits (both P < 0.001). Second, during IV remifentanil infusion, bilateral naloxone injections into the “tachypneic area” of the parabrachial nucleus reversed respiratory rate depression from 55 ± 9% to 20 ± 14% in young and from 46 ± 20% to 18 ± 27% in adult rabbits (both P < 0.001). The effects of bilateral [D-Ala,2 N-MePhe,4 Gly-ol]-enkephalin injection and IV remifentanil on respiratory phase duration in the “tachypneic area” of the parabrachial nucleus was significantly different from the pre-Bötzinger complex.

Conclusions: The “tachypneic area” of the parabrachial nucleus is highly sensitive to μ-opioid receptor activation and mediates part of the respiratory rate depression by clinically relevant administration of opioids.