Opioid-Induced Hyperalgesia: Is it Real?

Opioid-Induced Hyperalgesia (OIH): A Real Clinical Problem or Just an Experimental Phenomenon?

When higher doses of opiates are required to keep pain under control, why does no one mention the possibility of increased pain?

I’m surprised to find no hint about how the natural aging process will increase the severity of pain as it further deteriorates the existing conditions of a chronic illness.

Considering how little evidence there is for this phenomenon and how easily it could have alternate explanations, it’s pretty clear that this is merely used as an excuse not to prescribe opiates or take a patient off opiates when their pain increases.

Although opioid-induced hyperalgesia (OIH) is mentioned as a potential cause of opioid dose escalation without adequate analgesia,true evidence in support of this notion is relatively limited. 

Most studies conducted in the context of acute and experimental pain, which seemingly demonstrated evidence for OIH, actually might have measured other phenomena such as acute opioid withdrawal or tolerance. [how about increasing pain?] OIH studies in patients with chronic pain have used various experimental pain models (such as cold pain tolerance or heat pain intensity). Therefore, the fact that they have yielded inconsistent results is hard to interpret.

Thus far, with the exception of a few clinical case reports on OIH in patients with cancer pain and one prospective study in patients with chronic neuropathic pain, evidence for OIH in patients with chronic or cancer-related pain is lacking.

This study prompted me to find out more:
Opioid-induced hyperalgesia – Wikipedia, the free encyclopedia

Although tolerance and opioid-induced hyperalgesia both result in a similar need for dose escalation, they are nevertheless caused by two distinct mechanisms. The similar net effect makes the two phenomena difficult to distinguish in a clinical setting.

So far, it is not just “difficut”, but impossible to distinguish these two in practice.

Under chronic opioid treatment, a particular individual’s requirement for dose escalation may be due to tolerance (desensitization of antinociceptive mechanisms), opioid-induced hyperalgesia (sensitization of pronociceptive mechanisms), or a combination of both.

Again, the possibility of increasing pain is never considered.

Identifying the development of hyperalgesia is of great clinical importance since patients receiving opioids to relieve pain may paradoxically experience more pain as a result of treatment. Whereas increasing the dose of opioid can be an effective way to overcome tolerance, doing so to compensate for opioid-induced hyperalgesia may worsen the patient’s condition by increasing sensitivity to pain

The phenomenon is uncommon, mainly occurring among palliative care patients following a rapid escalation of opioid dosage.

Despite being uncommon, this phenomenon is often used as a reason not to prescribe opiates in the first place.


In examining the published studies on opioid-induced hyperalgesia (OIH), Reznikov et al criticize the methodologies employed on both humans and animals as being far-removed from the typical regimen and dosages of pain patients in the real world.

They also note that some OIH studies were performed on drug addicts in methadone rehabilitation programs, and that such results are very difficult to generalize and apply to medical patients in chronic pain.

It is now known that studies done in environments completely different from subjects’ normal circumstances are often skewed (like the mice held in individual cages without stimulation or contact with others).

In contrast, a study of 224 chronic pain patients receiving ‘commonly-used’ doses of oral opioids, in more typical clinical scenarios, found that the opioid-treated patients actually experienced no difference in pain sensitivity when compared to patients on non-opioid treatments.

The authors conclude that opioid-induced hyperalgesia may not be an issue of any significance for normal, medically-treated chronic pain patients at all.

It’s a crime that research dollars are being wasted on such an unlikely phenomenon, but because it supports the currently popular idea that “opiods are evil”, funding is probably easy to get.

Opioid-induced hyperalgesia has also been criticized as overdiagnosed among chronic pain patients, due to poor differential practice in distinguishing it from the much more common phenomenon of opioid tolerance.

The misdiagnosis of common opioid tolerance (OT) as opioid-induced hyperalgesia (OIH) can be problematic as the clinical actions suggested by each condition can be contrary to each other. Patients misdiagnosed with OIH may have their opioid dose mistakenly decreased (in the attempt to counter OIH) at times when it is actually appropriate for their dose to be increased or rotated (as a counter to opioid tolerance)

This can be a pain patient’s worst nightmare: as their need for pain medication increases, a doctor will decide to cut them off completely when they ask for more.  Many of us are very, very careful to never ask for more opioid medication. Sometimes we even hide the worsening of our pain just to make sure our doctor doesn’t suddenly decide it’s OIH and stops giving us our pain medication.

The suggestion that chronic pain patients who are diagnosed as experiencing opioid-induced hyperalgesia ought to be completely withdrawn from opioid therapy has also been met with criticism. This is not only because of the uncertainties surrounding the diagnosis of OIH in the first place, but because of the viability of rotating the patient between different opioid analgesics over time. Opioid rotation is considered a valid alternative to the reduction or cessation of opioid therapy, and multiple studies demonstrate the rotation of opioids to be a safe and effective protocol  

Here are two previous posts with experienced and well-known pain doctors expressing skepticism about the phenomenon of OIH:

Is Opioid-Induced Hyperalgesia a Real Phenomenon? by Jeffrey Gudin, MD

Thoughts on tolerance, hyperalgesia, and short-acting opioids by Jennifer P. Schneider, MD, PhD




5 thoughts on “Opioid-Induced Hyperalgesia: Is it Real?

  1. painkills2

    I might think hyperalgesia was real if I had experienced it myself during my almost 30 years as an intractable pain patient, or if I knew of anyone who suffered from it. Mostly, pain patients who have this fear are just mimicking what other people have told them, not because they have experienced it themselves.

    Liked by 3 people

  2. Pingback: Opioid-Induced Hyperalgesia: Is it Real? | All Things Chronic

  3. kmlund42

    I have Intractable Pain and suffer everyday, without the opiods I take I would of ended my life. How cruel can the the medical community be? Hyperalgesia has been their answer and I pray I don’t lose the pain doctor I already have. What are we suppose to do without opiods? I don’t see any real alternative that has even come close to working. It is inhumane for the medical community to watch another human stand by and suffer.

    Liked by 1 person

    1. Zyp Czyk Post author

      I hope you find comfort in that there are 5 to 8 million others using opioids to control their chronic pain.

      Slowly, doctors are starting to point this out and make a public stand defending opioid use for pain. You can see it if you look at the lastest articles posted here.


    2. Zyp Czyk Post author

      Hyperalgesia is just an excuse not to raise dosages as your condition worsens. Increasing tolerance is also used to explain the increasing pain we’ll suffer as we age.

      They just don’t want to treat pain because they can’t objectively measure it.



Other thoughts?

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )


Connecting to %s