TY - JOUR
T1 - Augmented breaths ('sighs') are suppressed by morphine in a dose-dependent fashion via naloxone-sensitive pathways in adult rats
AU - Bell, Harold J.
AU - Pankuch, Glenn
N1 - Funding Information:
This study received internal financial support in the form of laboratory start-up funds from the Department of Medicine, Penn State University College of Medicine . We thank Philippe Haouzi, MD, PhD for many thoughtful discussions on topics contained in this manuscript.
PY - 2013/1/5
Y1 - 2013/1/5
N2 - Morphine treatment can eliminate augmented breaths (ABs; 'sighs') during spontaneous breathing. In the present study, unanesthetized rats were studied to: (1) determine the involvement of naloxone-sensitive receptor pathways, and (2) establish the dose-response relationship of this side effect. At a dosage of 5mg/kg (2-10mg/kg is recommended range for analgesia) morphine eliminated ABs from the breathing rhythm across nearly 100min post-administration (vs. 6.2±1.6 ABs in 15min, control condition, p<0.001). This occurred despite no apparent effect on indices of ventilation. By contrast, when naloxone was co-administered with morphine, the occurrence of ABs was not different compared to control. The suppression of ABs by morphine followed a sigmoidal pattern across the low-mid dosage range (R2=0.83), whereas tidal volume and breathing frequency were unaffected. We conclude that the opioid-induced suppression of ABs is mediated by naloxone-sensitive opioid receptor pathways, and that this side effect is potent across the low-mid dosage range, and cannot be simply avoided by restricting dosage.
AB - Morphine treatment can eliminate augmented breaths (ABs; 'sighs') during spontaneous breathing. In the present study, unanesthetized rats were studied to: (1) determine the involvement of naloxone-sensitive receptor pathways, and (2) establish the dose-response relationship of this side effect. At a dosage of 5mg/kg (2-10mg/kg is recommended range for analgesia) morphine eliminated ABs from the breathing rhythm across nearly 100min post-administration (vs. 6.2±1.6 ABs in 15min, control condition, p<0.001). This occurred despite no apparent effect on indices of ventilation. By contrast, when naloxone was co-administered with morphine, the occurrence of ABs was not different compared to control. The suppression of ABs by morphine followed a sigmoidal pattern across the low-mid dosage range (R2=0.83), whereas tidal volume and breathing frequency were unaffected. We conclude that the opioid-induced suppression of ABs is mediated by naloxone-sensitive opioid receptor pathways, and that this side effect is potent across the low-mid dosage range, and cannot be simply avoided by restricting dosage.
KW - Dose-response
KW - Opioids
KW - Sighs
UR - http://www.scopus.com/inward/record.url?scp=84871919776&partnerID=8YFLogxK
U2 - 10.1016/j.resp.2012.09.014
DO - 10.1016/j.resp.2012.09.014
M3 - Article
C2 - 23043875
AN - SCOPUS:84871919776
VL - 185
SP - 296
EP - 303
JO - Respiratory Physiology and Neurobiology
JF - Respiratory Physiology and Neurobiology
SN - 1569-9048
IS - 2
ER -