Little evidence of opioid-induced hyperalgesia

Evidence of opioid-induced hyperalgesia in clinical populations after chronic opioid exposure: a systematic review and meta-analysis – Br J Anaesth. – 2019 Jun

Opioid-induced hyperalgesia (OIH) is well documented in preclinical studies…

It’s such a trendy topic that I’m sure many researchers are looking for evidence that chronic pain patients only need high doses because they are suffering from “opioid-induced hyperalgesia”, which has still NOT been proven in humans.

…but findings of clinical studies are less consistent.

This isn’t surprising to most pain patients, who know the difference between their increasing pain and hyperalgesia. 

The objective was to undertake a systematic review and meta-analysis of studies examining evidence for OIH in humans after opioid exposure.


Systematic electronic searches utilised six research databases (Embase, Medline, PubMed, CINAHL Plus, Web of Science, and OpenGrey). Manual ‘grey’ literature searches were also undertaken.

Wow, they were so certain it’s real that they looked into every possible nook and cranny of published research to find supporting evidence.

The Population, Interventions, Comparators, Outcomes, and Study design (PICOS) framework was used to develop search strategies, and findings are reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Data synthesis and subgroup analyses were undertaken using a random effects model (DerSimonian-Laird method).

Their search was certainly thorough, and this makes their findings very solid – low-quality evidence with inconsistent results. They didn’t find much of what they were looking for.


A total of 6167 articles were identified. After abstract and full-text reviews, 26 articles (involving 2706 participants) were included in the review.

  • There was evidence of OIH, assessed by pain tolerance, in response to noxious thermal (hot and cold) stimuli, but not electrical stimuli.
  • There was no evidence of OIH when assessing pain detection thresholds.
  • OIH was more evident in patients with opioid use disorder than in patients with pain, and in
  • patient groups treated with N-methyl-d-aspartate receptor antagonists (primarily evidenced in methadone-maintained populations).

Reading this (don’t have access to full study), it seems the only kind of pain that they found to qualify as “hyperalgesia” was from very hot or cold temperatures.

So the only problem they found is that taking higher doses of opioids makes us more temperature-sensitive. For us women, various kinds of medications, foods, or situations can make us more or less temperature-sensitive (usually involving estrogen levels).


OIH was evident…

If it was so evident, why didn’t they trumpet it in their results?

…in patients after chronic opioid exposure, but findings were dependent upon pain modality and assessment measures.

Does this surprise any pain patients? We know pain isn’t always the same from day to day, and sometimes even during the same day.

Pain patients know that rating pain on a scale from 0 to 10 isn’t really possible because so many variables affect the sensation of pain. But in most current research, all pain is regarded as a single uniform entity that varies only in its intensity, as measured at some random moment by a single-dimensional scale.

When a whole area of research, like the current swarm of studies on every imaginable negative consequence of opioids, rests on the invalid assumption that pain can be measured and represented on a simple scale, how can the results be considered valid?

Further studies should consider evaluating both pain threshold and pain tolerance across a range of modalities to ensure assessment validity.

And, since you cannot logically prove opioid-induced hyperalgesia does NOT exist, they are determined to keep conducting “further studies” until they find the results they want.

Significant subgroup findings suggest that potential confounders of pain judgements, such as

  • illicit substance use,
  • affective characteristics, or
  • coping styles,

should be rigorously controlled in future studies.

All the above affect our pain perception to some degree, and there are literally uncountable others that will no doubt be found as our understanding of pain increases.

So far, we’ve only established that pain can be either acute or chronic and neuropathic or nociceptive.

Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

3 thoughts on “Little evidence of opioid-induced hyperalgesia

  1. Charles Bruscino

    Hyperalgesia, Here’s what medical reductionsists might be/are probably missing. Opioids are very effective. A pain patient will become, generally, more physically active when prescribed opioids which will aggravate underlying pathology that causes the pain. Thus there is a increase in pain, maybe, for pain patients on opioids and we have to find a balance between increased functioning and the various risks associated with prescription opioids. The improved Quality of Life for prescription opioid patients is well worth the risks. Theoretically, we can titrate up indefinitely with “pure opioids”, i.e., no Ibuprofen or Tylenol added. “Scientists” want to find a reductionist or molecular answer for everything, to the exclusion of other explanations, and this defies common sense, common decency and common knowledge. I don’t need an ‘effin scientist to tell me I need to eat food and drink water every day.Oh, I’m trained in all major branches of science. Charles Bruscino

    Liked by 1 person

    1. Zyp Czyk Post author

      What you say makes perfect sense, and I’ve noticed it in myself. When my meds are working well and I’m in less pain than usual, I also become more active than usual, and then have a bit of a rough time recovering the next day.

      Less pain = more activity… and then perhaps a little more pain afterward. That’s what’s true for most of us I suspect. However, I still want to know who those people are that have *less* functionality and more pain when taking more opioids.

      Even setting aside the pain level (which is almost impossible to rate and compare from one day to the next) and focusing only on functionality, how can someone be *more* functional (which I assume corresponds to activity) when using less pain relief?

      I can only think this applies to those who shouldn’t even be taking opioids, whose pain isn’t really bad, and who become somnolent from the opioids because they are “overkill”. As soon as my pain lets up for any reason, I notice the relief when I start becoming much more active. Suddenly I’m motivated to clean things, do chores, exercise, talk to people, and do all those things I haven’t been doing because I often just feel lousy and everything hurts.

      It’s often only after finishing a chore like vacuum cleaning that I’ll realize my pain hasn’t been bad. I don’t notice pain relief in itself as much as I notice my sudden burst of activity.


  2. Pingback: Is Opioid Induced Hyperalgesia a Clinical Reality? | EDS and Chronic Pain News & Info

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