title: Endogenous opioid function mediates the association between laboratory-evoked pain sensitivity and morphine analgesic responses.
abstract: Predictors of responsiveness to opioid analgesic medications are not well understood. This study tested whether individual differences in endogenous opioid (EO) function are associated with analgesic responsiveness to morphine. In randomized, counterbalanced order over 3 sessions, 45 chronic low back pain participants and 31 healthy controls received an opioid antagonist (8 mg naloxone), morphine (0.08 mg/kg), or placebo. Participants then engaged in 2 laboratory-evoked pain tasks (ischemic and thermal). Outcomes included pain threshold, pain tolerance, and pain ratings. Indexes of EO function and morphine analgesic responsiveness were derived for each measure as the difference in pain responses between the placebo condition and naloxone or morphine condition, respectively. For all 7 pain measures across the 2 laboratory pain tasks, greater EO function was associated with significantly lower morphine analgesic responsiveness (P<0.001-P=0.02). Morphine reduced pain responses of low EO individuals to levels similar to those of high EO individuals receiving placebo. Higher placebo condition-evoked pain sensitivity was associated with significantly greater morphine analgesic responsiveness for 5 of 7 pain measures (P<0.001-P=0.02). These latter associations were significantly mediated by EO function for 4 of these 5 pain outcomes (all P values<0.05). In the laboratory-evoked pain context, opioid analgesic medications may supplement inadequate EO analgesia, with little incremental benefit in those with preexisting high EO function. Implications for personalized medicine are discussed.
authors.affiliation: Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA Department of Behavioral Science, Rush University, Chicago, IL, USA Department of Anesthesiology, Rush University, Chicago, IL, USA Department of Psychology, Ohio University, Athens, OH, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Bruehl
authors.forename: John W
authors.initials: JW
authors.lastname: Burns
authors.forename: Rajnish
authors.initials: R
authors.lastname: Gupta
authors.forename: Asokumar
authors.initials: A
authors.lastname: Buvanendran
authors.forename: Melissa
authors.initials: M
authors.lastname: Chont
authors.forename: Ellen
authors.initials: E
authors.lastname: Kinner
authors.forename: Erik
authors.initials: E
authors.lastname: Schuster
authors.forename: Steven
authors.initials: S
authors.lastname: Passik
authors.forename: Christopher R
authors.initials: CR
authors.lastname: France
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D010812:Physical Stimulation; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine
keywords: Chronic pain; Endogenous opioids; Mediation; Opioid analgesic; Pain; Personalized medicine