Is Opioid-Induced Hyperalgesia Lessened by Switching to Buprenorphine?

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Pressure pain threshold, pain tolerance, and pain intensity were measured via quantitative sensory testing.
Pressure pain threshold, pain tolerance, and pain intensity were measured via quantitative sensory testing.

In a prospective pilot study reported in the Journal of Nature and Science, researchers at the University of Michigan observed changes in several measures of pain in patients suspected of opioid-induced hyperalgesia (OIH) after transitioning from opioids to buprenorphine.1

In the 2016 Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain, the risk for OIH was noted as an area of concern in addition to the potential for opioid abuse and overdose.2 Previous findings by the investigators of the current study show that “patients on opioids with persistently high pain scores reported a phenotype consistent with having a more centralized pain state (fibromyalgia-like presentation), which suggests the potential presence” of OIH.3 Patients with suspected OIH and taking  >100 mg oral morphine equivalents (OME) were found to have lower pressure pain tolerance than those taking <100 mg OME.4

Although results of other recent studies indicate that buprenorphine may represent a viable alternative for patients with pain who are exhibiting opioid dependence, these studies did not use quantitative sensory testing or examine phenotypic changes.5,6 The present study investigated pressure pain sensitivity and pain phenotyping in 20 patients transitioning from full µ-opioid agonists to buprenorphine for the treatment of suspected OIH.

Phenotyping was assessed using self-report measures such as the Brief Pain Inventory, the Hospital Anxiety and Depression Scale, and the Catastrophizing Subscale of the Coping Strategies Questionnaire, which patients completed at multiple points from baseline to 6 months after buprenorphine initiation. In addition, pressure pain threshold, pain tolerance, and pain intensity were measured via quantitative sensory testing. The most common daily buprenorphine dosage ranged from 2 to 16mg.

No significant associations were found for patients who had been receiving < 100 mg OME (n = 13) at baseline. However, patients receiving an OME ≥ 100mg regimen (n = 7) displayed significant improvements in pain severity, fibromyalgia scores, neuropathic pain, catastrophizing, depressive symptoms, and functioning 1 week after the transition to buprenorphine  (P <.05 or less for all); these scores ultimately returned to baseline. There was a trend toward reduced pressure sensitivity in the high-OME group at the 1-week mark, although this did not reach statistical significance and also returned to baseline.

These findings suggest buprenorphine may eventually lead to similar hyperalgesic effects of a full µ-opioid agonist and thus “it may be best to wean patients off of opioids altogether rather than to continue them on buprenorphine long term,” the researchers stated. However, they noted that the study “excluded patients with a history of addiction, which may benefit from continued buprenorphine therapy regardless of the pain effects.” Future research should aim to replicate these results in larger cohorts.

Summary and Clinical Applicability

Alhough buprenorphine reduced measures associated with opioid-induced hyperalgesia after 1 week of treatment, these ultimately returned to baseline levels.

Limitations and Disclosures

Limitations of the study include the small sample size, significant attrition rates, the lack of a gold standard for diagnosing OIH, and the use of self-report questionnaires.

Three of the authors report having received research funding and consulting fees from various companies listed in the paper, and Dr Harte is a co-inventor of the MAST device that was used in the present research

 

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References

  1. Wasserman RA, Hassett AL, Harte SE, et al. Pressure sensitivity and phenotypic changes in patients with suspected opioid-induced hyperalgesia being withdrawn from full mu agonists. J Nat Sci. 2017; 3(2). pii: e319.
  2. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain - United States, 2016MMWR Recomm Rep. 2016; 65(1):1–49. doi: 10.15585/mmwr.rr6501e1
  3. Wasserman RA, Brummett CM, Goesling J, Tsodikov A, Hassett AL. Characteristics of chronic pain patients who take opioids and persistently report high pain intensityReg Anesth Pain Med. 2014; 39(1):13–7. doi: 10.1097/AAP.0000000000000024
  4. Wasserman RA, Hassett AL, Harte SE, et al. Pressure pain sensitivity in patients with suspected opioid-induced hyperalgesiaReg Anesth Pain Med. 2015; 40(6):687–93. doi: 10.1097/AAP.0000000000000315
  5. Daitch J, Frey ME, Silver D, Mitnick C, Daitch D, Pergolizzi J., Jr. Conversion of chronic pain patients from full-opioid agonists to sublingual buprenorphinePain Physician. 2012; 15(3 Suppl):ES59–ES66.
  6. Roux P, Sullivan MA, Cohen J, et al. Buprenorphine/naloxone as a promising therapeutic option for opioid abusing patients with chronic pain: reduction of pain, opioid withdrawal symptoms, and abuse liability of oral oxycodonePain. 2013; 154(8):1442–1448. doi: 10.1016/j.pain.2013.05.004

 

 

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