The Opioid Crisis: Nociception, Pain and Suffering

The Opioid Crisis: Nociception, Pain, and Suffering – Jun 2016 – By Martin Samuels, MD

This article offers an excellent explanation of how pain works and how opioids function just like our own endogenous opioids.

In order to understand the concept of pain and its relationship to the current opioid crisis, it is prudent to review the neurology of pain an why it exists.  

Several concepts are important to integrate.


Nociception is the capacity to sense a potentially tissue damaging (noxious) stimulus.    

To illustrate this one should place a forefinger in a glass of ice water and determine how long passes until an unpleasant sensation arises.  

If one performs this experiment in a large group, one can recognize that, although the stimulus is the same (a glass of ice water), the sensation arises at different rates in different people.

In fact, a bell shaped curve will describe the distribution in any population of people.  Within 30 seconds almost all will have perceived an unpleasant sensation that is known at pain.  Nociception is a very primitive sensation.

It is present in virtually all animals, even those without a brain, such as Aplysia, the sea slug.

Controlling Nociception:  

Why is it that a noxious stimulus ‘”wears off?”  Why does the unpleasant sensation not go on forever?  

A system has evolved that is designed to turn off the nociceptive system.  

This signal arises in the brain and releases a chemical that turns off the nociceptive impulses just after they enter the central nervous system

This chemical is one of two small peptides, known as enkephalins, which bind to opioid receptors

Because these are made in one’s own nervous system they are known as endogenous opioids.  

Thus opioids are natural substances that are critical for controlling nociception so that the pain does not last beyond its use, which is to signal the presence of noxious stimuli.

Opioids are widespread in nature.  

Many centuries ago, human being learned that there was something in poppies that relieved pain.  That substance was an opioid.

All natural and synthetic opioids have a very similar chemical structure and they all work by turning off the nociceptive system.

Those that come from sources outisde of one’s own nervous system are termed exogenous opioids.


Pain is discomfort caused by injury.

It is a phenomenon that arises in a part of the brain known as the thalamus, a cluster of nuclei in the center of the head (the centrencephalon).

The thalamus is the way station for virtually all sensation coming from the outside world, whether noxious or not

The thalamus is constantly weighing the amount of noxious vs non-noxious information coming from the surrounding world.  When noxious stimuli exceed non-noxious ones, pain is the sensation experienced.

Pain allows one to consciously recognize that there is a potentially tissue damaging stimulus in the environment.  As such it is critical to health and even survival.  

Pain that lasts beyond the experience of nociception has sometimes been called chronic pain, though it is better to think of it as a form of suffering.


Suffering is the experience of undergoing pain, hardship or distress.

Note that pain is only one of the causes of suffering.  Some others might be: war, poverty, marital discord, mental illness, work dissatisfaction, anxiety and depression, just to name a few.

Suffering is a complex phenomenon that requires a high level brain.

Phenomena common to the use of many drugs:  

Several phenomena occur with drug use.

Tachyphylaxis is said to occur when increasing doses of a drug no longer produce greater effects.

Amphetamines, such as the street drug methamphetamine or many diet drugs, have this characteristic.  Tachyphylaxis occurs when the mechanism of a drug is the release of a preformed substance (e.g. catecholamines) from nerve endings.  When that substance is depleted, additional drug can have no incremental effect.  In other words, tachyphylaxis is sudden tolerance that is not dose dependent.

Tolerance means that, over time, increasing doses of the drug are required to produce a equivalent effect.

Opioids (eg codeine, morphine, oxycodone), alcohol and benzodiazepines (eg diazepam, lorazepam) have this characteristic.

When there is tolerance, the person will experience symptoms and signs of withdrawal when the dose of the drug is reduced or it is discontinued.  

Tolerance is due to reduced number or sensitivity of drug receptors effected by exposure to the drug.  Everyone who uses a drug of this type will develop some degree of tolerance and withdrawal.

Addiction implies a craving or obsession.

Drug addiction means that the person becomes obsessed with the drug and spends inordinate amount of effort and time in attempts to obtain it, even including illegal and dangerous activities.  The system in the brain that leads to addiction uses a different chemical, dopamine,

Thus it is important to realize that addiction can be due to tolerance and withdrawal but not necessarily so.

People vary with respect to how susceptible they are to obsessiveness and addiction.

Just as we can demonstrate the variation in the experience of pain after putting one’s finger in a glass of ice water, one can prove that a bell shaped curve describes the tendency in a population of people to develop addictions.

This means it’s far from certain that a person will develop an addiction just because they are exposed to addictive drugs.

Addictive drugs do not cause addiction.

The essential problem:  

The essential problem underlying the opioid societal issue is that various forms of suffering are being routinely treated as if they were pain due to nociception.

Opioids have their very important place, but it is their side-effects that cause the deaths in people who are using them to treat their suffering, including suffering caused by chronic pain.

As a side effect, opioids can cause coma and stop breathing, thus causing death.  They also may stimulate the dopamine reward system, leading to addiction.

It is thus critically important for the medical and lay communities to understand the proper place for opioids.

Put simply, exogenous opioids are needed when the noxious stimulus is sufficiently intense that endogenous opioids are not adequate.  

See “Opioids, Endorphins, and Euphoria” for a more detailed explanation of how opioid pain medication supplements our endogenous opioids to enhance pain relief.

A long bone fracture would be a good example.  Bone metastates might be another.  In both circumstances the longevity of the pain will be time-limited.

When endogenous opioids are not adequate to relieve a time-limited pain, exogenous opioids are the treatment and doctors must prescribe them.   

Simply legislating limits on opioid prescribing does not address the essential problem.

Reducing suffering is much more complex and challenging than relieving pain.  It requires time, empathy and wisdom.  Machines do not possess the necessary attributes to relieve suffering.  Only people have those attributes

In the comments, I found that doctors hold the dangerous assumption that opioids control pain by changing how you feel about the pain.

This makes absolutely no sense in light of the article, which describes how opioid medication is just an enhancement of our own endogenous opioids.

William Palmer MD:

Some guesses: Opiods don’t exactly reduce pain directly compared to local anesthesia, eg, wherein the threshold is actually increased

This is completely the opposite of what the article just pointed out: opioids, both external and endogenous, are the body’s antinociceptive molecules.

They seem to, rather, bring on a sense of well-being that is so pleasant that one doesn’t mind the pain–which actually becomes a somewhat different sensation, almost like a tickle or itch in the background of euphoria. It seems as if they change the pain.

This is the effect of marijuana/cannabis, not opioids.

I’m alarmed that a doctor can make such a glaring logical error about how opioids function is scary. This comes when someone indulges in

Such “magical thinking” is needed to make sense of the anti-opioid lobby’s claims that opioids are not effective for chronic pain.

2 thoughts on “The Opioid Crisis: Nociception, Pain and Suffering

  1. painkills2

    “Reducing suffering is much more complex and challenging than relieving pain. It requires time, empathy and wisdom.”

    And money. Don’t forget money. Money that no one wants to contribute to relieve society’s pains. No, we spend billions of dollars on the drug war instead.

    “Machines do not possess the necessary attributes to relieve suffering. Only people have those attributes.”

    There isn’t another person in the world who could relieve my pain. Used to be a doctor could help me do it, but that’s no longer true. Without a prescription pad, doctors are useless. And there’s nothing all of us poor people can do to help each other — we’re too busy surviving.

    I was also alarmed by what I read in the comments. Believe me, I wish cannabis was a painkiller like opioids. However, I know plenty of patients who do claim that weed reduces their pain. This appears to be more about perception. Weed increases your ability to distract yourself from the pain, but it doesn’t “kill” the pain. The pain isn’t reduced. But, it does help pain patients to be more physically and emotionally active, which may result in some pain reduction. And I think weed may prove to be a painkiller for certain types of pain and for certain pain patients.

    “Opiods don’t exactly reduce pain directly compared to local anesthesia, eg, wherein the threshold is actually increased”

    Anesthesia increases your pain threshold? Perhaps for as long as the anesthesia is in effect, but the pain is still there. After the anesthetic wears off, your pain threshold is the same. There may even be some rebound pain and inflammation when the nerves awaken, like after surgery or dental work. Like it or not, opioids do reduce pain. I think what some pain patients need to learn is that there are limits to what they can do. Just like there are limits to what anesthetics and antidepressants can do.

    Liked by 1 person

  2. Pingback: Summary of Posts about the Opioid Crisis | EDS Info (Ehlers-Danlos Syndrome)

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