Background & Aims
Although opioid analgesics can be quite effective for pain management, their risks in both the acute and chronic pain settings are well known (e.g., opioid use disorder, overdose, and death). One approach to mitigating opioid risks is precision pain medicine in which opioid analgesics may be targeted at individuals likely to obtain good pain relief with low risk of adverse effects and opioid misuse1. Precision pain medicine requires understanding of predictors of opioid responses and, ideally, the mechanisms underlying those predictive effects. A series of studies in our lab found that low endogenous opioid (EO) function, indexed by changes in pain in response to opioid receptor blockade, predicted elevated analgesic responsiveness to a weight-adjusted dose of i.v. morphine(2,3,4,5). This study sought to replicate these findings and extend them to oral oxycodone, an opioid analgesic commonly used in the outpatient postoperative setting.
Methods
The sample included 36 individuals with chronic low back pain (58% female; mean age = 43 years) not using opioid analgesics . Participants underwent three laboratory sessions during which they engaged in an ischemic (ISC) pain task and a heat pain task after receiving either oral oxycodone (0.13 mg/kg) + i.v. saline placebo, i.v. naloxone (8 mg) + oral placebo, or i.v. saline + oral placebo. Measures included pain threshold and tolerance, intra-task NRS pain intensity (ISC only), and MPQ-SF ratings obtained immediately following each task. The MPQ SF-2 was used to rate low back pain intensity pre-post drug in each condition. Greater EO analgesia was indexed by increased evoked pain following naloxone relative to placebo Greater oxycodone analgesia was indexed by greater decreases in pain after oxycodone relative to placebo. Similar clinical EO analgesia and oxycodone analgesia measures were derived based on pre-post drug changes in low back pain intensity.
Results
For the ISC task, lower EO analgesia was associated (r’s = 0.54 – 0.69; p’s < .001) with greater analgesic responses to oxycodone across all measures (pain threshold/tolerance; NRS intensity; MPQ-SF Sensory, Affective, and Total scores; Present Pain Intensity; VAS intensity). There was a 1.5 SD difference in oxycodone analgesia between the lowest and highest 25th percentile of EO function (VAS). For the heat pain task, similar inverse associations between degree of EO analgesia and oxycodone analgesic responses were noted for pain threshold and tolerance, MPQ-SF Affective score; Present Pain Intensity; and VAS intensity (r’s = 0.51 - 0.64; p’s < .003). Clinical pain outcomes showed effects similar to evoked pain outcomes. Lower EO inhibition of low back pain was associated with significantly greater oxycodone analgesic effects on low back pain across all MPQ SF-2 subscales (Continuous, Intermittent, Neuropathic, Affective) and the total score (r’s = 0.37 - 0.91; p’s < .03).
Conclusions
Results replicate prior work demonstrating greater analgesic responsiveness to opioid analgesics in those with lower EO system inhibitory function(2,3,4,5), and extend these findings from intravenous morphine to oral oxycodone. Given the common clinical use of oxycodone for postsurgical pain management, the current study has relevance to understanding factors driving postoperative pain management responses. Individuals with low natural pain inhibitory capacity obtain significantly greater pain relief with oxycodone. Prior work indicates that higher depression, anxiety, and catastrophizing levels predict greater opioid analgesic responsiveness via their associations with lower EO function(6). As surrogate measures of EO status, these phenotypic variables could serve as mechanistic predictors of opioid analgesic responses in potential precision medicine algorithms.
References
1. Bruehl et al. Personalized medicine and opioid analgesic prescribing for chronic pain: opportunities and challenges. J Pain. 2013; 14: 103-13. PMC3564046.
2. Bruehl et al. Endogenous opioid function mediates the association between laboratory-evoked pain sensitivity and morphine analgesic responses. Pain. 2013; 154: 1856-1864. PMC4069065.
3. Bruehl et al. Reg Anesth Pain Med. 2014; 39: 120-5. PMC3933525.
4. Bruehl et al. The association between endogenous opioid function and morphine responsiveness: a moderating role for endocannabinoids. Pain. 2019; 160: 676-687. PMC6377294.
5. Bruehl et al. Does aerobic exercise training alter responses to opioid analgesics in individuals with chronic low back pain? A randomized controlled trial. Pain. 2021; 162: 2204-2213. PMC8203753.
6. Burns et al. Psychosocial factors predict opioid analgesia through endogenous opioid function. Pain. 2017; 158: 391-399. PMC7176103.
Presenting Author
Stephen Bruehl
Poster Authors
Topics
- Treatment/Management: Pharmacology: Opioid