I was told by someone who should know (as they must manage post-operative pain) that opioids lower a person's pain threshold, period. I had never heard that before, and I was doubtful that the statement was correct.

As someone who studied the effects of opioids to become buprenorphine certified (when it was new), was the medical director of a drug and alcohol rehab facility (not a big deal) and ran a free inner city drug/alcohol/mental illness clinic (a big deal for me) as well as an ED doc (one major role of which is to manage pain), I thought I understood opioids pretty well, so was alarmed at this person's insistence that it was a known fact. I questioned whether perhaps they were referring to tachyphylaxis, the development of tolerance, the phenomenon of people on methadone maintenance having a decreased pain threshold, the occasional case of paradoxical decrease in pain threshold following perioperative fentanyl administration or opioid induced hyperalgesia (OIH), and several other circumstances in which opioids don't relieve pain as expected, to which they answered no.

It was pretty concerning to me that I wasn't aware of this. Granted, I haven't been keeping up on the literature about opioids specifically or pain in general. So I started searching the literature.

OIH has been described in the literature since the 1870-80s, and the most common conclusions seem to be that its mechanism is unknown, the incidence is unknown, it can be difficult to differentiate from tolerance, it occurs more often in certain populations (chronic users/addicts/people on methadone), etc.

The literature is (what a surprise) all over the place concerning the response of pain to opioids, but no where did I find a general opinion regarding opioids reducing a person's pain threshold in general, or even an opinion leaning towards that.

I'm hoping someone on this site with more knowledge on the subject can give me a more reliable response than the one I recently received. Do opioids in fact decrease a recipients' pain threshold without regard to special circumstances?

Edited to add: I should note that a number of review articles noted that healthy (non-using) volunteers given a single dose of an opioid had an ~2x increase in area of forearm skin sensitivity to a cold pressor test compared to controls, but that other modalities of pain production were mostly unaffected.

Edited to add: I forgot to include this very comprehensive review: A Comprehensive Review of Opioid-Induced Hyperalgesia

  • 1
    I can't prove it's not true, but as someone else who routinely uses these drugs in clinical practice it's not something I've come across either.
    – Michael
    Dec 7, 2023 at 14:24
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    Their statement seems too hyperbolic to attempt to evaluate; I suspect they'll twist their statement to adapt to any counter-evidence provided in order to continue being "right". For example, it could range from "at any dose for any period of time, all opioids lower pain thresholds" which seems a bit absurd (if nothing else, you could use a homeopathic dose to prove it wrong), to something also difficult to prove but far less absurd like "all opioid drugs can lower pain thresholds if given at sufficient concentration for sufficient time".
    – Bryan Krause
    Dec 7, 2023 at 14:35
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    @BryanKrause "...if given at sufficient concentration for sufficient time", exactly, which is the case with addicts, people treated with opoids chronically for non-cancer pain, etc. OIH can in fact be countered by rotating the opioids used, raising further issues, as well as which opioid is administered, fentanyl being the biggest offender. I believe you know far more about this than I do, so it's nice to have this response. Also, the only argument that can conceivably (to me) be used for that blanket statement is the cold pressor studies... Dec 7, 2023 at 15:03
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    I found this to be a rather nice review as well: Wilson SH, Hellman KM, James D, Adler AC, Chandrakantan A. Mechanisms, diagnosis, prevention and management of perioperative opioid-induced hyperalgesia. Pain Manag. 2021 Apr;11(4):405-417. doi: 10.2217/pmt-2020-0105. PMCID: PMC8023328. It appears that opioid induced hyperalgesia (in the cold pressor test) appears to be a stable and reversible phenotype (meaning that patient characteristics, i.e. secondary gain in chronic pain patients or learned helplessness) does not play a role. AFAIK low temperatures also activate the same polymodal
    – Narusan
    Dec 8, 2023 at 15:00
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    [cont'd] type-C nociceptors, so the model has some validity to study pain thresholds (and might be easier to do in a clinical setting than electrical stimulation, where you also have to deal with synaptic depression and LTP if you continue to increase voltage), and one could generalise the Norwegian cohort study to say that opioids lower pain thresholds across a population - but I agree with Bryan that this would be a bit unnuanced. For sure, even OIH is still heavily disputed in the literature and there are neither good preclinical or clinical mechanistically studies addressing it.
    – Narusan
    Dec 8, 2023 at 15:03


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