Dr. Launette Rieb (biography and disclosures)
What I did before
In 2003 a 39 year old male crane operator with a history of a severe crush injury to the left upper limb came to me for treatment of profound allodynia and hyperalgesia (among other symptoms) that had spread from his injury site to all four limbs. He had been diagnosed with Chronic Regional Pain Syndrome and had undergone treatment attempts of all types for years. He was on high dose, long acting oxycodone 20 mg 6 tablets tid = 360 mg/d (morphine equivalent of approximately 540 mg/d). To try to get analgesic control (pain rating 10/10), and eliminate pill burden I rotated the oxycodone to fentanyl. Ultimately he required fentanyl 50 + 25 mcg patches every 3 days (morphine equivalent of approximately 150 mg/d) plus short acting oxycodone 5 mg qid prn for breakthrough (morphine equivalent of 30 mg/d). Not only did his pain drop down to a rating of only 1-2/10, the signs and symptoms of hyperalgesia and allodynia vanished. In just three weeks he went back to work. This perplexed me so I began searching the literature.
What changed my practice
I found the review article by J. Mao listed below and some other related studies that described Opioid Induced Pain Sensitivity (OIPS), which likely played a key role in the pain presentation of the worker described. Basically, some people manifest symptoms of diffuse spreading pain along with signs of allodynia and hyperalgesia when exposed to high doses of opioids (usually above 3-4 gm/d morphine equivalent, but it can happen at lower doses). The article reviews various lines of evidence, proposes mechanisms and treatments for this condition.
Treatments for OIPS can include opioid rotation or opioid lowering – both of which occurred in the worker reviewed above (ie. 540 -180 = 360 mg drop in the daily morphine equivalent dose, and opioid rotation from oxycodone to fentanyl). Some patients need to come right off the opioid for at least 2-4 weeks to see a change in signs and symptoms. Using an NMDA antagonist like ketamine or dextromethorphan when initiating an opioid can be helpful in preventing OIPS (though the latter two medications have issues of their own and I rarely use them). Methadone is an NMDA receptor antagonist through one of its isomers, the other isomer being a strong Mu opioid receptor agonist. Thus methadone (and to some extent buprenorphine) is a great choice for neuropathic pain patients where OIPS may be playing a role. Care is needed with the conversion between opioids, especially methadone or buprenorphine, since the NMDA glutamate system is involved in both the development of tolerance and OIPS, and conversion doses do not rise linearly. A good reference for conversions is listed below.
What I do now
OIPS is now something I consider whenever I see a patient with allodynia and hyperalgesia, whereas prior I may have simply tried to increase the opioid dose (which would help if tolerance alone was present). I’ve now taken many patients off opioids altogether or done one of the other maneuvers mentioned above and had both signs and symptoms clear. Also, I have found this to be true for some patients who were taking just moderate doses of opioids, far lower than the studies indicate, as with the crane operator above. Thus it is worth considering OIPS in the differential diagnosis when pain appears to be spreading, especially when features of allodynia and hyperalgesia are present.
References: (Note: Article requests require a login ID with CPSBC or UBC)
- Mao J. Opioid induced pain sensitivity: Implications in clinical opioid therapy. Pain 2002;100:213-217. (View article with CPSBC or UBC)
- McPherson, M.L. Demystifying opioid conversion calculations: A guide for effective dosing. American Society of Health-System Pharmacists, Bethesda, MD, 2009. (book: Woodward library, call number: QV89 .M478 2010)
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Thank you for this—I have encountered this problem several times, and in the terminally ill this can be confusing but a switch to another opioid has always worked for me in this setting.
Very informative narrative, I will definitely include OIPS in my differential of patients on narcotics presenting with an exaggerated pain response.
Interesting !
learned something new
Still a little confused how to recognize and treat this pain presentation.
I will definitely consider this approach.
I practice in a remote rural community with many first nations people. Many of them seem to have lower back pain after MVS’s and uses opioids on an ongoing and frequently abuse basis. How can one practice real medicine if you are manipulated and abused to prescribe what the patient request. This is very frustrating to remote rural physicians. I find your article informative but not easy to implement. I wish I could conform.
I will certainly consider this in this situation
interesting – although practically speaking may be difficult to implement
I have apatient with severe diabetic leg neurapathy on high doses of Journista who is developing widespread pain. He does not tolerate the adhesives in fenatanyl and butrans. How do I switch to methadone or is there another opiod you would suggest
will be cognizant of this possibility, although I already will try to rotate opioids if one doesn’t seem to be working
To consider, might be challenging to implement.
I have encountered this clinical situation several times when asked to provide advice to disability managers regarding injured employees who experience spreading or escalating levels of pain and become totally disabled for work. This explanation makes more than a little common sense to me and I will definitely consider it in the future.
JAW.
very interesting. I have found some patients with this pattern, but was not aware that the opiods could be contributing to the pain. I will now try a different approach.
very good advice. I will try it.
This is a VERY rare phenomenon. I am sorry but this is just seems to be a trick to reduce opioid use. Nice try. The DEA intrusion into medicine has caused many pain syndrome patients to suffer. I believe there is a better way to get these medications off the streets. I say this because as a health care provider I have encountered many pain syndrome patients who are now unable to access the medications they need.