Highlights
- •Persons with opioid dependence underwent pain testing during oxycodone maintenance.
- •Analgesic testing occurred at stabilization and 6 weeks later.
- •Oxycodone produced euphoric effects and miosis without robust analgesia.
- •Differential tolerance is important for treatment of pain and opioid use disorder.
Abstract
A common clinical problem with opioid analgesics is the loss of analgesic efficacy
after repeated dosing; when this occurs, it is not clear what principles should guide
providing effective analgesia among opioid-dependent individuals. This within-subject
inpatient study aimed to determine if physically dependent opioid abusers (n = 11)
experience changes in oxycodone-induced analgesia during 2 oxycodone maintenance (30 mg
orally 4 times per day) phases: initial stabilization (days 1–3) and after 6 weeks
of chronic dosing. Six sessions (3 each phase), measured threshold, tolerance, and
pain ratings for a Pressure Pain Test and Cold Pressor Test after a single double-blind
dose of oxycodone 30 mg (initial stabilization) and 0, 30, and 60 mg (chronic dosing)
given in place of a scheduled maintenance dose. Physiologic and opioid agonist effects
were assessed during chronic dosing sessions. There was no analgesic response to oxycodone
30 mg. Oxycodone (60 mg) produced a 25% increase in peak Cold Pressor Test threshold
compared with placebo, and significantly increased expired breath CO2, miosis, and
ratings of abuse liability measures. These data suggest that more than twice the acute
oxycodone maintenance dose is needed to produce robust acute analgesia, although adverse
effects (eg, respiratory depression and abuse signals) may occur with lower doses.
Perspective
To understand sensitivity to opioid analgesia in opioid-dependent individuals, this
article describes experimental pain, subjective and physiological responses during
stabilization and after 6 weeks of oxycodone maintenance. Oxycodone produced euphoric
effects and miosis with limited evidence of analgesia.
Key words
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Article info
Publication history
Published online: March 05, 2017
Accepted:
February 20,
2017
Received in revised form:
January 26,
2017
Received:
November 17,
2016
Footnotes
This work was supported by the National Institute on Drug Abuse (R01 DA016718-04; S.L.W.), (T32 DA01676; M.A.C.); and the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health (UL1TR000117).
P.A.N. has received statistical consultant fees from Braeburn Pharmaceuticals and the Behavioral Pharmacology Research Unit, The Johns Hopkins University. M.R.L. has received research funding and consultant fees from Braeburn Pharmaceuticals, consultant fees from Indivior, and honoraria from PCM Scientific for giving educational talks. S.L.W. has served as a consultant to World Meds, Inc, Braeburn Pharmaceuticals, KemPharm, Lightlake Therapeutics, INSYS, Astra Zeneca, Sun Pharma, and Cerecor, Inc, contract research support from Braeburn Pharmaceuticals and Cerecor, Inc, and received speaker and conference chair honoraria from PCM Scientific through an unrestricted educational grant from Indivior. M.A.C. has no conflicts of interest to declare.
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© 2017 by the American Pain Society
