“Buprenorphine is a kappa receptor antagonist. For these reasons, buprenorphine might be unique in its ability to treat chronic pain and possibly OIH.”
The opioid crisis has been fueled by the use of opioids to treat chronic pain. Practice patterns have changed, but doctors are still criticized for their roles in the overuse of opioids. I’ve sat through community ‘heroin forums’ (sometimes on stage) as sheriffs, politicians, and ‘recovered addicts’ firmly pointed fingers at health professionals. I, meanwhile, kept my finger under the table, but had the thought that some of the people pointing would be the first to complain if they were forced to stop pain medication prematurely for their own good or ‘for the good of the community.’
Doctors can’t see into the future. I suspect most cases of opioid overuse began with well-intended efforts to provide temporary pain relief. But then for a variety of reasons things didn’t go as planned. Maybe the planned knee or back surgery never took place because of patient indecision or insurance problems. Maybe the lumbar strain didn’t heal after 6-8 weeks the way it was supposed to. In any case, doctors who work with pain patients know what happens next. Before the next appointment, the doctor plans to tell the patient that the time has come to stop opioids. But after that suggestion, the patient replies that the pain is even worse now than when the pain meds were started. “Actually (says the patient) I was going to ask you to increase the pain medication!”
Some doctors hold fast to their plan and initiate a taper. Some doctors argue over the issue, and some manage to create enough fear in the office that no patient would dare talk back. Too often, patients are suddenly cut off high doses of opioids, precipitating withdrawal symptoms that drive them toward illicit pills or heroin. Patients who manage to maintain scripts for opioids embark on a miserable journey that often ends badly.
I’ve converted many pain pill patients to buprenorphine patients over the years. I could save time using a rubber stamp to document their histories: (blank)-year-old man was started on pain pills after (blank) injury (blank) years ago; dose was increased over time using oxycodone then OxyContin then fentanyl patches; patient lost the ability to control the medications and ran out early, resulting in discharge from treatment. Patient presents asking for treatment with buprenorphine.
Many past patients fit this description, riding the gray area between opioid dependence and pain. Lawmakers and policy-writers seem to believe that most patients are either addicts or pain patients. Doctors who work in the field know that most patients sit in the middle, with smaller groups on each side. **
I’ve been surprised at how well those pain patients do after changing to buprenorphine. They usually feel much better overall, which is no surprise given the misery of living according to a cycle of relief and withdrawal. More surprising is that their pain is reduced, sometimes completely. I assume the reduction in pain relates to stopping the cycle of relief and withdrawal, although I don’t know the mechanism beyond that idea. People who take opioids become more ‘somatic’ over time, more and more focused on symptoms including those that warn of impending withdrawal; perhaps buprenorphine reduces that tendency toward somatization.
Which brings us to opioid-induced hyperalgesia or ‘OIH’, where prolonged use of opioids makes pain symptoms worse. I’m reluctant to go ‘all in’ on OIH, just as I reserved full judgement of the full range of symptoms blamed on TMJ, EBV, IBS, CFS, FM, MCS, WPW, PMS, PMDD, RSD, CRPS, RLS, GAD, SAD, DID, IED, and other ‘initialed diseases’ that have garnered headlines over the years. (Can you name them all? *** Try THESE ) Attention on OIH has waxed and waned over the years, and is gaining attention now as PROP, the CDC, and SAMHSA talk down opioid use.
But seriously, my problem with OIH starts with awareness that pain sensation is very complicated. Different people describe varying pain intensity for the exact same stimulus. And even within one patient, intensity varies according to mood, fear, the duration of the pain (expected and actual), the perceived reason for the pain, the perceived harm from the stimulus, the setting (e.g. home vs. laboratory), and many other variables. It is one thing to see how long it takes a rat to flick its tail when placed over a heat lamp, but another when a human fills out a pain scale.
I also take note of selection bias, a phenomenon that occurs whenever science bumps into political forces where studies citing the occurrence of a phenomenon are more likely to get government funding and editor approval than studies denying the phenomenon. And no, I’m not a denier—of anything. But I know bias when I see it. I’ve seen articles that conclude ‘there is not enough evidence to rule OUT the existence of OIH’, which is the opposite of how good science is supposed to be conducted.
You’ll find a great review of OIH here: http://www.painphysicianjournal.com/current/pdf?article=MTQ0Ng%3D%3D&journal=60
A cautious reader of the literature will note that at best, OIH is more of a ‘basic science’ phenomenon than a ‘clinical phenomenon.’ Increased pain sensitivity in response to opioids is subtle. If it wasn’t, it would have been described decades, even centuries ago. The linked material references older comments that the authors suggest came from observations of OIH, but to my reading the comments more likely referred to the withdrawal that follows opioid use. You’ll also notice, if you read the linked article, that most of the studies of OIH in humans look at pain sensitivity in long-term methadone patients. But you’ll also read that in theory, methadone is one of the least-likely opioids to cause OIH.
Interestingly, the other opioid agent with lower likelihood to cause OIH is… buprenorphine. From the link above: Buprenorphine has been shown to be intermediate in its ability to induce pain sensitivity in patients maintained on methadone and control patients not taking opioids. Buprenorphine showed an enhanced ability to treat hyperalgesia experimentally induced in volunteers compared to fentanyl. And spinal dynorphin, a known kappa receptor agonist, increases during opioid administration, thus contributing to OIH. Buprenorphine is a kappa receptor antagonist. For these reasons, buprenorphine might be unique in its ability to treat chronic pain and possibly OIH.
In short, long term use of opioids appears to increase pain sensitivity. But we are a long way from understanding the extent of that phenomenon. Some studies suggest that all opioids are not equal in regard to OIH, and I wonder if the reported decrease in pain from relatively minor injuries such as lumbar strain, when people change from opioid agonists to buprenorphine, is caused by a decrease in opioid-induced hyperalgesia.
But then again, maybe those patients just thought they had pain because of a subconscious (or conscious) desire to get pain pills.
For whatever reason, people with chronic pain seem to do well on buprenorphine. Hopefully all of the concerns over opioids will leave us at least that one treatment option. Give the extreme safety of buprenorphine, that should be a no-brainer!
**At least that was the case until several years ago, when I began seeing more and more patients who ‘started heroin recreationally’- an oxymoron if there ever was one.
***TMJ = temporomandibular join disorder, blamed for chronic headaches and other symptoms; EBV = Epstein Barr Virus; IBS = irritable bowel syndrome; CFS = chronic fatigue syndrome; FM = fibromyalgia; MCS = multiple chemical sensitivity; WPW = Wolf Parkinson White; PMS = premenstrual syndrome; PMDD = premenstrual dysphoric disorder; RSD = reflex sympathetic dystrophy; CRPS = complex regional pain syndrome; RLS = restless leg syndrome; GAD = generalized anxiety disorder; SAD = seasonal affective disorder; DID = dissociative identity disorder; IED = intermittent explosive disorder.