Faculty Collaboration Database

Clinically relevant infusion rates of mu-opioid agonist remifentanil cause bradypnea in decerebrate dogs but not via direct effects in the pre-Bötzinger complex region. J Neurophysiol 2010 Jan;103(1):409-18

Date

11/13/2009

Pubmed ID

19906886

Pubmed Central ID

PMC2807229

DOI

10.1152/jn.00188.2009

Scopus ID

2-s2.0-74049097521 (requires institutional sign-in at Scopus site)   52 Citations

Abstract

Systemic administration of mu-opioids at clinical doses for analgesia typically slows respiratory rate. Mu-opioid receptors (MORs) on pre-Bötzinger Complex (pre-BötC) respiratory neurons, the putative kernel of respiratory rhythmogenesis, are potential targets. The purpose of this study was to determine the contribution of pre-BötC MORs to the bradypnea produced in vivo by intravenous administration of clinically relevant infusion rates of remifentanil (remi), a short-acting, potent mu-opioid analgesic. In decerebrate dogs, multibarrel micropipettes were used to record pre-BötC neuronal activity and to eject the opioid antagonist naloxone (NAL, 0.5 mM), the glutamate agonist D-homocysteic acid (DLH, 20 mM), or the MOR agonist [D-Ala(2), N-Me-Phe(4), gly-ol(5)]-enkephalin (DAMGO, 100 microM). Inspiratory and expiratory durations (T(I) and T(E)) and peak phrenic nerve activity (PPA) were measured from the phrenic neurogram. The pre-BötC was functionally identified by its rate altering response (typically tachypnea) to DLH microinjection. During intravenous remi-induced bradypnea (approximately 60% decrease in central breathing frequency, f(B)), bilateral injections of NAL in the pre-BötC did not change T(I), T(E), f(B), and PPA. Also, NAL picoejected onto single pre-BötC neurons depressed by intravenous remi had no effect on their discharge. In contrast, approximately 60 microg/kg of intravenous NAL rapidly reversed all remi-induced effects. In a separate group of dogs, microinjections of DAMGO in the pre-BötC increased f(B) by 44%, while subsequent intravenous remi infusion more than offset this DAMGO induced tachypnea. These results indicate that mu-opioids at plasma concentrations that cause profound analgesia produce their bradypneic effect via MORs located outside the pre-BötC region.

Author List

Mustapic S, Radocaj T, Sanchez A, Dogas Z, Stucke AG, Hopp FA, Stuth EA, 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
Edward J. Zuperku PhD Professor in the Anesthesiology department at Medical College of Wisconsin

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

Action Potentials
Analgesics, Opioid
Animals
Brain Stem
Decerebrate State
Dogs
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
Excitatory Amino Acid Agonists
Female
Functional Laterality
Homocysteine
Male
Microinjections
Naloxone
Narcotic Antagonists
Neurons
Phrenic Nerve
Piperidines
Respiratory Rate
Time Factors