title: Neuromodulatory effect of endogenous opioids on the intensity and unpleasantness of breathlessness during resistive load breathing in COPD.
abstract: BACKGROUND
  Endogenous opioids are naturally occurring peptides released by the brain in response to noxious stimuli. Although these naturally occurring peptides modulate pain, it is unknown whether endogenous opioids affect the perception of breathlessness associated with a specific respiratory challenge. The hypothesis is that intravenous administration of naloxone, used to block opioid signaling and inhibit neural pathways, will increase ratings of breathlessness during resistive load breathing (RLB) in patients with chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  Fourteen patients with COPD (age, 64 ± 9 years) inspired through resistances during practice sessions to identify an individualized target load that caused ratings of intensity and/or unpleasantness of breathlessness ≥ 50 mm on a 100 mm visual analog scale. At two intervention visits, serum beta-endorphins were measured, naloxone (10 mg/25 ml) or normal saline (25 ml) was administered intravenously, and patients rated the two dimensions of breathlessness each minute during RLB.
  
  
  RESULTS
  Patient ratings of intensity (p = 0.0004) and unpleasantness (p = 0.024) of breathlessness were higher with naloxone compared with normal saline. Eleven patients (79%) reported that it was easier to breathe during RLB with normal saline (p = 0.025). RLB led to significant increases in serum beta-endorphin immunoreactivity and decreases in inspiratory capacity. There were no significant differences in physiological responses between interventions.
  
  
  CONCLUSIONS
  Endogenous opioids modulate the intensity and the unpleasantness of breathlessness in patients with COPD. Differences in breathlessness ratings between interventions were clinically relevant based on the patients' global assessment.
authors.affiliation: Section of Pulmonary & Critical Care Medicine, Dartmouth Medical School, Lebanon, New Hampshire 03756-0001, USA.
authors.forename: Alex H
authors.initials: AH
authors.lastname: Gifford
authors.forename: Donald A
authors.initials: DA
authors.lastname: Mahler
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Waterman
authors.forename: Joseph
authors.initials: J
authors.lastname: Ward
authors.forename: William J
authors.initials: WJ
authors.lastname: Kraemer
authors.forename: Brian R
authors.initials: BR
authors.lastname: Kupchak
authors.forename: John C
authors.initials: JC
authors.lastname: Baird
mesh_terms: D000368:Aged; D000403:Airway Resistance / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007320:Inspiratory Capacity / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D011897:Random Allocation; D012119:Respiration / Q000187:drug effects*; D001615:beta-Endorphin / Q000097:blood / Q000502:physiology*
chemical_list: D009292:Narcotic Antagonists; D009270:Naloxone; D001615:beta-Endorphin