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Pontine μ‐opioid receptors mediate the bradypnea caused by clinically relevant rates of intravenous remifentanil in dogs
Author(s) -
Prkic Ivana,
Mustapic Sanda,
Radocaj Tomislav,
Stucke Astrid G.,
Stuth Eckehard A.,
Hopp Francis A.,
Dean Caron,
Zuperku Edward J.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1088.10
Subject(s) - damgo , chemistry , anesthesia , opioid , medicine , enkephalin , receptor
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 mu‐opioid receptors (MORs) within the respiratory control network are responsible. The purpose of this study was 1) to define the pontine region in which MOR agonists produce bradypnea and 2) to determine whether antagonism of those MORs reverses bradypnea produced by IV remifentanil (remi; 0.1–1.0 μg/kg/min). The effects of microinjections of agonist [D‐Ala2, N‐Me‐Phe4, Gly‐ol5]‐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 5–7 mm lateral of midline and from 0–2 mm caudal of the inferior colliculus at a depth of 3–4 mm. During remi‐induced bradypnea (71.5±3.6% reduction in breathing rate; 21 dogs) NAL microinjections (860±69 nl each) within the region defined by the DAMGO protocol were able to reverse bradypnea (47.2±5.2%/injection) with 13 of 84 injections producing complete reversal. Histological examination of dye injections shows that the sensitive region corresponds to the parabrachial Kölliker‐Fuse complex. Supported by VA Medical Research Funds.