It might be a cliché to say this, but everyone hurts in their own way. Two people may suffer the same injury, but one might feel a lot of pain, and the other might not. One long-distance runner could keep running despite discomfort that would cripple another.
Our innate ability to endure pain is so immense that it may well be considered a superpower. And it comes from our body’s ability to produce its very own supply of opioids. Within all of us is a universe of opioids and receptors that mediate not just all that hurts but all that pleases. The spectrum of pain and pleasure, the push and pull of desire and disgust, the very question that vexed Socrates, is primarily a measure of the balance of endogenous opioids in our bodies.
Balance in the endogenous opioid system is the key to our feeling of normality, of peaceful stillness in the moment. When we take opioid pills or injections, that balance is changed, and for some, the change is permanent.
Opioid receptors are widely distributed in the human nervous system and, indeed, have likely been present in vertebrates for at least 450 million years. When Patrick Wall and Ron Melzack conceived their gate theory of pain in 1965, while their overall hypothesis was sound, they knew little about the actual components of the pathways they proposed that pain traveled on. We know now that endogenous opioids are the keys to the gates that pain has to pass through to be felt.
The first and perhaps most important parts of the body’s endogenous opioid system are the receptors that opioids like morphine bind to. Initially called the Mµ receptors, they were recently rechristened as MOP. The primary internal opioid that acts on MOP is called beta-endorphin.
When stimulated in the midbrain, MOP receptors send signals down to the spinal cord, slamming the door on painful nociceptive signals attempting to ascend the nervous system toward the brain. And this is how opioids essentially work: they overwhelm these gates, shutting them tight, preventing nociception from transforming into pain by reaching the brain.
Beta-endorphin is more than our very own painkiller. It is also the key facilitator of the feeling one gets when eating a delicious meal or making love or when holding one’s child really close. Endorphins are the chunk of cheese at the end of the maze, the summit at the end of the trek, the trophy at the end of the tournament.
The endogenous opioid system is also closely linked to our stress response system – one might well be the yin to the other’s yang. Understanding this relationship is important to achieving a greater understanding of both chronic pain and the effects of opioid use on how we feel.
While in everyday parlance, stress has a decidedly negative connotation, our body’s ability to respond to crises is critical to its survival. When we encounter the sight or even the smell of a predator, hormones like cortisol and norepinephrine mobilize our immune system, raise our blood pressure and heart rate, and increase our attentiveness. The same intricately evolved response helps us fight off a serious infection. Yet a persistent stress response is linked to depression and posttraumatic stress disorder, as well as heart disease, obesity, and irritable bowel syndrome, to name just a few. Therefore, after a stressor subsides, we need to douse the flames of the stress response, and that’s where endogenous opioids come into play.
When we feel stressed, our body produces a molecule that is split into ACTH, a stress hormone, and beta-endorphin, our chief endogenous opioid. So even as the stress response is revving up, our inner opioids modulate how extreme that response will be and how quickly we will recover from it. The influx of endogenous opioids during stress is also why we feel less pain during a calamity, allowing a wounded soldier to escape the battlefront. In one experiment, novice parachutists showed decreased pain sensitivity because of the anxiety they felt, an effect that went away when they were given a drug that blocked the effects of opioids. Our inner opioids serve to take the edge off, to satiate, to unplug.
Yet just as modern life is characterised by chronic rather than acute pain, the same is true of stress. Instead of the occasional predator, today’s stressors are an incessant barrage of work emails, the escalating demands of domestic life borne increasingly by the individual rather than shared by the community, and rising anxiety wrought by a world that is increasingly digitally connected but interpersonally fractured. This state of constant stress causes us to continually produce endogenous opioids, both rendering their antistress properties less potent and inducing opioid dependence, which increases our sensitivity to everyday nags and nicks. An ache that might never even be registered by the person at peace might crush the person under duress.
Even as chronic stress can predispose people to developing chronic pain, chronic opioid use can make the problem worse. This might be surprising because, given how central endogenous opioids are to our own ability to kill pain, one would surmise that prescription opioids would be a panacea for chronic pain. Yet a recent review of 162 studies by the US Agency for Healthcare Research and Quality showed that for patients with chronic pain, opioids were barely better than placebo at alleviating pain or restoring physical function and no different at improving mental well-being. And they were no better than nonopioid pain medications like acetaminophen (Tylenol) or ibuprofen. This lack of benefit was accompanied by significant harm and a plethora of side effects.
The reason opioid medications don’t work for chronic pain is that they are simply too blunt and too powerful, rocking the delicate balance of the body’s natural pain-regulation systems. Even a relatively small dose of a drug like morphine or oxycodone dwarfs the amount of beta-endorphin our body can produce by itself. To our body, a prescription dose of opioids is like a snowstorm in Texas, overwhelming the infrastructure. And so the body goes to work to restore equilibrium by reducing the number of opioid receptors, which dulls the impact of the drugs. This is why, over time, we develop a tolerance for opioids and need a higher dose to achieve the same effect.
Yet this change has another more insidious effect: chronic use of opioids leads our body to produce less of its own endogenous opioids and other related chemicals.
This makes people who take opioids more likely to experience exaggerated stress responses that are not counterbalanced by endogenous opioid production, which also means it takes them longer to recover from such episodes. The link between depression and chronic pain is also mutually reinforcing. People with depression are more likely to produce lower amounts of endogenous opioids, helping explain why opioid drugs often help depressed people feel better; however, by causing a reduction in endogenous opioid production, chronic opioid use further suppresses their ability to feel better on their own, which further deepens their depression.
Excerpted with permission from The Song of Our Scars: The Untold Story of Pain, Haider Warraich, HarperCollins India.
