My last few posts have been about addictions. As I’ve wrote them, I started to reflect on the evolution of pain management and the role of opioids over my lifetime in medicine, 1977 through 2021.
I apologize in advance if I come off sounding like an “old geezer” regaling my audience with tales of “I remember when… (fill in the blank)”. Clearly, “state of the art” knowledge has shifted over time in response to new discoveries, market pressures, and cultural shifts. However, newer isn’t always better, and movement isn’t aways progress.
I hasten to point out that I’m not a pain expert or an addictions expert. I’m writing from the perspective of a practicing physician who was trying to do the best for my patients while staying reasonably current with “best practice”. Beyond that, I was a Physician Peer Reviewer for a while, which let me see how other doctors managed similar issue for their patients, and I later became a regional department head with responsibility for some pain services, which gave me another perspective. In sum, over the years I have looked at the problem “bottom up” and “top down”.
It seems to make sense to break this into four (maybe more) posts, as follows:
the 70’s, when I was in medical school and learning the theory. This sets the foundation.
the 80’s, when I went into practice and the focus seemed to be on acute pain and cancer pain, while trying to limit iatrogenic, meaning “medically induced”, addictions.
the 90’s and 00’s, when the focus shifted to chronic non-malignant pain and the use of opiates increased, arguably leading to the current opioid crisis.
the 10’s and 20’s, when societally we’ve been dealing with the aftermath. In this post, I’ll also discuss some of the “lessons learned” and the things we’ve forgotten along the way.
So, without further ado, here’s Part 1.
I attended medical school in Calgary, Alberta in the late 70’s, graduating in 1980.
The medical school was newish and the curriculum was somewhat experimental. We had one learning stream organized around specific body systems and a parallel stream dedicated to more general topics, like pain, some of which got more emphasis than others.
Pain, in other words, was one topic among a great many.1
The thinking at the time was inspired by “Pain Mechanisms: A New Theory”, authored by Ronald Melzack and Patrick Wall in 1965. That seminal article summarized the two prevailing theories of pain, noting that neither one fully explained all of the available research. Without getting lost in the details, the author’s new Gate Control Theory proposed that:
Various sensory “inputs” from the periphery travelled through nerves to the spinal cord, where those messages could either be blocked, amplified, or distorted before carrying on to the brain to be interpreted, sometimes as “pain”.
Pain did not originate in specific pain receptors, it did not travel through dedicated pain nerves, and there was no dedicated pain centre in the brain.
All sorts of sensory inputs could be interpreted as being painful, depending on what happened to the message in the spinal cord and brain.
For example, even gentle sustained pressure might be labelled as pain by someone who was over-tired, depressed, or otherwise “sensitized”. Furthermore, pain might interrupt sleep, creating a vicious cycle where the pain became worse as the sleep deteriorated.
The ultimate conclusion was that pain management was not simply a matter of blocking painful stimuli at the source or en route to the brain. Rather, pain management could (indeed should) consider the full range of biological, psychological, and social factors.
Building on that, in 1979 the International Association for the Study of Pain (IASP) approved a consensus definition of pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage".2 That definition still stands 45 years later. The important takeaways were (and still are) that pain:
is always subjective, and each of us learns the meaning of the word “pain” through experience.
is a physical sensation in a part or parts of the body, AND
it is always unpleasant, making it also an emotional experience.
implies actual or potential tissue damage, BUT
may or may not reflect any actual tissue damage.
The literature of the time includes examples of painful conditions.
There’s the obvious, like pain resulting from actual tissue damage due to trauma, electric shocks, burns and lacerations. At the same time, it’s known that tissue damage (or “noxious stimuli”) can occur without triggering the pain experience, one example being soldiers who deny pain despite horrific injuries. As the IASP phrased it, “Activity induced …by a noxious stimulus is not pain, which is always a psychological state, even though we may well appreciate that pain most often has a proximate physical cause.” So, painful looking things are usually painful, but not always.
And, while pain usually results from nasty painful stimuli, some pain has no obvious local cause. Various pain syndromes are caused by altered transmission of sensory inputs, creating the mental impression of tissue damage, but without any actual damage at the perceived site of the pain. Many of these diagnoses reflect nerve damage due to trauma or infection, and have been recognized for centuries, including:
causalgia, a severe burning pain that may result from a partial lesion of a peripheral nerve, first described in the 1500’s by Ambroise Paré who was treating French King Charles IX of Valois,
phantom limb pain, which may occur after amputation of a limb, also described by Paré, and
neuralgias, such as trigeminal neuralgia, first described by John Fothergill in 1783.
Other conditions, like migraine headaches (described by Hippocrates, although not called migraines until later) are obviously painful, even though the cause isn’t really known and there is no “proximate physical cause”.
In addition, there is pain relating to cancer, resulting from actual tissue damage (i.e. cancer invading tissues), and/or damage to nerves (i.e. cancer invading or compressing nerves).
Finally, the IASP noted that while tissue and/or nerve damage and the experience of pain were usually related, “Many people report pain in the absence of tissue damage or any likely pathophysiological cause; usually this happens for psychological reasons. There is no way to distinguish their experience from that due to tissue damage if we take the subjective report. If they regard their experience as pain and if they report it in the same ways as pain caused by tissue damage, it should by accepted as pain. This definition avoids tying pain to the stimulus.” In other words, some people could “experience” and report pain (and should be accepted as being “in pain”) without there being actual tissue damage, usually as a consequence of some sort of “psychological reasons”, which they didn’t explain.
As I look back on the articles I can find from that time, I don’t see a lot of differentiation between acute and chronic pain. The emphasis seemed to be on the experience of pain, not the duration.
So, to summarize the state of pain knowledge when I was in medical school3:
if someone says they are in pain, you have to believe them.
pain is an unpleasant physical AND emotional experience.
pain most often does have a “proximate physical cause” (meaning actual or potential tissue damage), but
some people with injuries don’t report pain, and
some people feel pain without any actual tissue damage (including things like migraines, but “usually” for psychological reasons).
pain management should address any tissue damage present as well as the patient’s emotional experience (or “psychological state”).
Pain management built on that theoretical foundation:
First, manage the symptom (pain) while fixing the cause (damaged tissue, if present). Don’t just give analgesics! Suture the laceration, treat the burn, splint the fracture, etc. Acute pain should resolve as the tissue heals, generally within three months at most.
Second, for the pain syndromes not associated with tissue damage, like migraines and neuropathies, make a diagnosis and then tailor the treatment to the cause, where and if specific treatments exist. Trigeminal neuralgia, for example, is treated with a drug called carbamazepine.
Third, treat the problem AND the emotional experience. If, for example, the patient is worried that their pain means they have a fatal disease, simple reassurance may be all that’s needed, if their problem is actually benign.
Finally, primum non nocere, meaning “do no harm”. This basic medical principle reminds all physicians that for any problem, it may be better not to do something, or even to do nothing, rather than risk causing more harm than good. Put another way, don’t “overtreat”.
And that brings us to the pain medication options, which were pretty limited.
ASA was the mainstay of the over-the-counter medications. By the 70’s, ASA was known to have anti-inflammatory properties, making it the first of the non-steroidal anti-inflammatory drugs (NSAIDs). Developed by Bayer in the late 1800’s and marketed worldwide starting in 1899, it wasn’t until 1971 that a British pharmacologist showed how ASA actually worked, exerting its effects in the tissues (i.e. at the “source” of the pain).4
Acetaminophen was also invented in the late 1800’s but concerns about its toxicity5 delayed its release and general acceptance. It started to see widespread use only in the 1970’s, eventually surpassing ASA in the 80’s. Acetaminophen has little or no anti-inflammatory effect, but, like ASA, it is thought to exert its analgesic effect in the tissues.
In terms of other options, ibuprofen was first marketed in the United States in 1974, while naproxen followed in 1976, both being NSAIDs like ASA. The only other NSAID at the time was indomethacin, which was approved for medical use in 1963. It was seen as having worrisome side-effects, so, practically speaking, its use was restricted to specific “time-limited” situations (like acute gout) or cases where other NSAIDs had failed. Of note, in the 70’s and 80’s indomethacin, ibuprofen and naproxen were NOT available over-the-counter, but ONLY as prescription drugs. All were marketed as anti-inflammatory drugs, NOT as analgesics, so they were to be used in situations involving inflammation. In order to get the anti-inflammatory effect, you had to take the right dose, on a regular schedule, for long-enough to build up therapeutic levels in the inflamed tissues. At least, that was the theory. However, because they also have analgesic effects, it wasn’t surprising for some patients to feel better even without their inflammation settling. Other patients taking an NSAID for an inflammatory problem, like rheumatoid arthritis, might report that their other painful conditions, like tension headaches, had also improved.
Finally, there were the opiates. Unlike the NSAID’s, opiates exert their pain-killing effects in the spinal cord and/or brain. They’ve have been known as painkillers for centuries and were even prescribed by Hippocrates.
Back in the 70’s, the commonest opiates in medical use were believed to have a hierarchy of “strength”, with codeine being the least powerful and morphine the “strongest”. In between there was meperidine (Demerol) and oxycodone (marketed in combination with ASA as Percodan or acetaminophen as Percocet).6 The “evil cousin”, the opiate known as heroin (proper name diamorphine), was available most places only as a drug of abuse.7
In general terms, back then opiates were reserved for the short-term management of severe pain, or for patients dying of cancer. This was “do no harm” in action. Opiates were known to be addictive, so they were prescribed only when needed for acute or maybe intermittent pain, in the lowest effective dose for the shortest time possible, or for cancer palliation, where the poor prognosis outweighed any addiction concerns.
So, as I said, in the 70’s the analgesic medication options were limited. ASA or acetaminophen for mild pain, “weak” opiates for moderate pain, and “strong” opiates for more severe pain. Opiates were for short term use, intermittent use, or palliation, NOT for long term regular use. Heroin was for addicts.
Testing the theory and practice
While in medical school, I sprained my ankle. I’ve seen a lot of sprained ankles since then, but few if any ever looked as bad as mine, so I would have to conclude that I did some major damage to the joint.8 I had the full physical and emotional experience. It was PAINFUL in a way that I’ve never experienced before or since!
The emergency doctor reassured me that nothing was broken, taped it up badly and sent me home, with nothing for pain and no crutches. I tried ice and elevation overnight, to no avail. Hopping around on one foot made it worse.
The next day my preceptor brought me some crutches and handed me a bottle of 292’s from his sample cupboard. Back then, I guess, drug reps handed out free samples of opiates, and they weren’t kept under lock and key!9 292’s included a combination of ASA, codeine and caffeine. In theory, the ASA and codeine worked together to reduce pain, while the caffeine augmented the pain-killing properties, offset the drowsiness caused by the codeine, or maybe both. However, the amount of caffeine was 15mg per pill, an amount that pales in comparison to the 95mg found in a typical cup of coffee these days, so it’s hard to imagine the caffeine in 292’s actually doing anything.
The 292’s took the edge off my pain, which was helpful at bedtime. I didn’t notice losing touch with reality, but I did drive through a stop sign, narrowly avoiding a collision.
I concluded that primum non nocere meant not doing anything requiring brain power while taking 292’s. I went with the “stiff upper lip”, choosing pain over danger, and that ended my career as an opiate user.10
In my next post, I’ll talk about the 80’s, when I set up practice in Dartmouth, Nova Scotia, and started to put pain theory into practice.
I remember there being lectures, and the sources they quoted. I admit that I understand them better in hindsight than I did at the time.
I haven’t been able to access the original article, so I’m quoting from this article which references and quotes the original.
This is NOT quite the same as saying that this is what I personally knew at the time!
When I was in medical school, it was still standard practice to treat rheumatoid arthritis with massive doses of ASA, based on its anti-inflammatory effects. The premise was that you ramped up the dose of ASA until the inflamed joints improved or the patient could no longer tolerate the burning in their stomach or the ringing in their ears, those being the commonest side-effects. It was horrible, but the alternatives were corticosteroids (which have their own lengthy list of complications) or phenylbutazone, a drug no longer used in humans because it can cause the bone marrow to shut down.
There’s very little difference between the usual dose of acetaminophen and the dose that can destroy your liver!
The idea that some opiates are “weak” and others are “strong” hasn’t held up over time. In general, they all work the same way, and they are all addictive.
Interestingly, heroin was first brought to the medical market by Bayer in 1898, but they ceased production in 1913 after its addictive potential was recognized. You might wonder why it was thought to be so different from all the other opiates, which are also addictive. You also have to marvel at Bayer choosing NOT to market an addictive drug. Compare and contrast with the behaviour of Purdue in marketing their drug OxyContin.
I was swollen and deeply bruised from the tips of my toes right up to the knee, and the bruising took a good 6 weeks to resolve.
A behind-the-counter version, the 222, had a bit less codeine, and was readily available on request at every pharmacy. As I write this, I also wonder why drug reps would be handing out samples of pain killers to a general medical specialist who spent most of his time doing cardiology.
Unsurprisingly, 292’s are no longer available. “Combination” pills have generally fallen out of favour, acetaminophen has triumphed over ASA, and “better” (meaning more profitable) opiates have come along. You can, however, still get combination pills containing acetaminophen and codeine (Tylenol #3, for example).
Rick - loved this. As someone who has been working in primary care (ER and FM) in CB (hotbed of prescription opioid addiction) and specifically has done "complex pain management" with injury patients for many years, I think pain is the most interesting (and badly done) part of medicine. Great to read this, and very interested to read the next in the series.
Interesting! I have shared with my CMIO who is also an anesthesiologist/intensivist.