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Pontine μ-opioid receptors mediate bradypnea caused by intravenous remifentanil infusions at clinically relevant concentrations in dogs. J Neurophysiol 2012 Nov;108(9):2430-41

Date

08/10/2012

Pubmed ID

22875901

Pubmed Central ID

PMC3545180

DOI

10.1152/jn.00185.2012

Scopus ID

2-s2.0-84868322892 (requires institutional sign-in at Scopus site)   72 Citations

Abstract

Life-threatening side effects such as profound bradypnea or apnea and variable upper airway obstruction limit the use of opioids for analgesia. It is yet unclear which sites containing μ-opioid receptors (μORs) within the intact in vivo mammalian respiratory control network are responsible. The purpose of this study was 1) to define the pontine region in which μOR agonists produce bradypnea and 2) to determine whether antagonism of those μORs reverses bradypnea produced by intravenous remifentanil (remi; 0.1-1.0 μg·kg(-1)·min(-1)). The effects of microinjections of agonist [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enkephalin (DAMGO; 100 μM) and antagonist naloxone (NAL; 100 μM) into the dorsal rostral pons on the phrenic neurogram were studied in a decerebrate, vagotomized, ventilated, paralyzed canine preparation during hyperoxia. A 1-mm grid pattern of microinjections was used. The DAMGO-sensitive region extended from 5 to 7 mm lateral of midline and from 0 to 2 mm caudal of the inferior colliculus at a depth of 3-4 mm. During remi-induced bradypnea (~72% reduction in fictive breathing rate) NAL microinjections (~500 nl each) within the region defined by the DAMGO protocol were able to reverse bradypnea by 47% (SD 48.0%) per microinjection, with 13 of 84 microinjections producing complete reversal. Histological examination of fluorescent microsphere injections shows that the sensitive region corresponds to the parabrachial/Kölliker-Fuse complex.

Author List

Prkic I, Mustapic S, Radocaj T, Stucke AG, Stuth EA, Hopp FA, Dean C, Zuperku EJ

Authors

Astrid G. Stucke MD Professor in the Anesthesiology department at Medical College of Wisconsin
Eckehard A. Stuth MD Professor in the Anesthesiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Analgesics, Opioid
Anesthetics, Intravenous
Animals
Brain Mapping
Diaphragm
Dogs
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
Hyperoxia
Infusions, Intravenous
Naloxone
Narcotic Antagonists
Phrenic Nerve
Piperidines
Pons
Receptors, Opioid, mu
Respiratory Rate