The misinformation about pain control began in a 2004 paper, “Pleasure Into Pain: The consequences of long-term opioid use” by Australian J.M. White. https://www.ncbi.nlm.nih.gov/pubmed/15345267
To reach the absurd conclusion that despite the observed facts that opioids work for chronic pain and that people are stable on them for many years, the drugs must not really work, White had to ignore 50% of what’s known about opioids.
The brain has a pleasure center in the nucleus accumbens. Tickling that pleasure center distracts people from unpleasantness. And as we get used to a certain level of opioids in our bodies, we don’t notice the tickling anymore, which frustrates drug abusers because they no longer feel high.
The 50% White had to ignore, was the nociception center in the brain’s periaqueductal grey matter, which functions as a smart router or switch for incoming pain signals from every part of the body. Nociception ignores meaningless pain signals, like the throbbing pain in your belly that you feel after a surgeon has cut you to remove an infected gall bladder. But nociception instantly spots the difference between meaningless pain, and new, differently-patterned pain signals that indicate something is wrong…such as the pain that you feel by rolling over in bed and pulling on your surgical stitches. Nociception sends that pain on through to your cognitive awareness. You feel the hurt. You remember not to turn over. Your surgical wound heals for a couple of weeks and eventually you no longer have pain.
Opioids affect nociception, too. But what’s different in their effect on nociception, is that the effect is constant. The reason it is constant, is that one’s sensations of meaningless pain are also constant. Only if a painful disease gets worse, causing increased pain, does the brain need more opioids to deal with the increased pain.
When we deny the brain it’s accustomed supply of opioids, the increased workload on the nociception process tires the brain out, causing the range of symptoms we know as opioid withdrawal. For many years it had been noticed that people who suffer illness and go on bed rest for several days, have symptoms similar to that of opioid withdrawal, but it’s due to withdrawal of the pleasurable sensations associated with physical movement. Addicts still suffer withdrawal, long after they’ve stopped feeling pleasure from tickling the brain’s pleasure center, and by ignoring the normal process of nociception, JM White managed to mislead everybody as to why withdrawal happens. (He speculated that the opioids magically make the nerves more sensitive to pain. A lot of people who should have been smart enough to know better, believed him.) But JM White’s theory of opioid hyperalgesia, fails to explain why a person who gets the flu and spends 3 days in bed, feels discomfort from exercise withdrawal.
Many other folks who noticed that exercise withdrawal caused symptoms like that of opioid withdrawal, speculated that the body secreted a substance, named “Endorphin”, that was associated somehow with physical exercise. Two years after JM White’s nonsensical article hyping his hyperalgesia theory, Rougeot and Wisner at the Pasteur Institute in Paris, found a candidate substance that formed in our salivary glands, that they called “Opiorphin”, which was thought to be the elusive Endorphin. Soon hundreds of scientists began trying to identify what Opiorphin was.
What they all discovered, is that Opiorphin is Morphine, say SUNY professors George Stefano and Richard Kream in this review article Arch Med Sci 2010; 6,5 pp. 658–662.The elusive substance turns out to form in all our cells. It’s formed in all animal and plant cells. It’s used to regulate the metabolism of food.
Since no one is truly morphine-naive, the discovery that we’re constantly in the presence of low-level morphine, explains a lot.
For one thing, we’re not constantly high. That’s a consequence of the brain’s pleasure center adapting to the presence of endogenous morphine.
For another, we feel withdrawal symptoms when we sit still too long. That has health significance too. Our lymphatic systems require our muscles to move, so that fluids are squeezed out of our various tissues and moved through our lymph nodes. Without this squeezing action, toxins accumulate in our lymph and are not removed. Feeling those withdrawal symptoms gets us bored enough that we start moving around, just for the pleasure of movement, and our lymphatic fluids get filtered as they move through lymph nodes.
Yet another, is that the body requires raw materials with which to make morphine. Those raw materials appear to be tyrosine and tyramine, two amino acids that occur in beans, beer, cheese, and a variety of other foods.
Stefano, Kream, et al, Folia Biologica Praha 58, pp 49–56 (2012).
The synthesis process for making morphine in the body appears complicated and produces 13 other substances, among them dopamine, a substance associated with emotional excitement.
And yet another mystery about the opioid drugs, is that codeine, hydrocodone, hydromorphone, oxycodone and others, are removed from the body by enzymatic oxidation using the liver’s cytochrome P450 enzyme and various other “Phase I” liver enzymes. Many of these enzymatic pathways lead to morphine as an intermediate product. But morphine is not further degraded. The body processes morphine with “Phase II” liver enzymes. (A discussion of Phase I and Phase II drug metabolism can be found on Wikipedia at https://en.wikipedia.org/wiki/Drug_metabolism). Morphine is attached to glucose, making it water-soluble and passing it through the bloodstream to the bile and urine. Drug Metab Dispos.1997 Jan;25(1):1–4.
By this route, morphine seems to by recycled in the body, saving our cells the expense of making it from tyrosine and tyramine.
It’s long been observed that addicts who buy street drugs, tend to be in poor health. Since street drugs are expensive, addicts don’t have money left over to spend on nutritious food, and that may be complicating their illness in ways we don’t yet anticipate.
Is it possible that some of the 13 precursor substances, on the synthetic pathway from tyrosine and tyramine, to morphine, have other uses in our bodies, that we don’t yet recognize as important? That’s certainly possible. If that’s true, then it’s also possible that when the addict is creating a surplus of recycled morphine, by detoxification of the drugs of abuse, and starving himself of necessary nutrients because nutritious food is too expensive after paying street prices for drugs, a shortage of the 13 morphine precursor substances could develop.
Perhaps the main health benefit of inpatient rehabilitation for addicts, is that the addicts get fed hospital food and their food metabolism becomes more normal.
Certainly the typical pain patient who can get prescription opioids for pain, has no need to starve or eat out of garbage cans, and the wasting syndrome that finally drives homeless, starving addicts into an emergency room for help, simply does not appear in the chronic pain population, except in cases such as celiac disease or certain cancers, where the patient’s illness itself interferes with digestion and nutrition.
The hyperalgesia myth is not supported well, by the research on which it was based. What’s been learned in the last 13 years has demolished it thoroughly. It’s high time we scrap the idea and move on to where the scientific findings lead us. And that leads us toward a healthcare model that takes patients seriously when they say they hurt or feel bad.