The past two centuries have produced a cascade of life-altering advances in medicine, yet we have been unable to deal with one seemingly straightforward condition: chronic pain. It affects 1 in 5 people around the world, yet in large part because of a fundamental misunderstanding of its basic nature, it remains poorly treated.
Our failure to understand pain is most clearly exemplified in the opioid epidemic. While opioid medications are effective in treating patients with acute pain, such as the type one develops after breaking a limb, the cumulative evidence suggests that they are no better at helping patients with chronic pain — generally defined as pain that lasts for six months or more — than safer painkillers such as ibuprofen or acetaminophen.
Prescription opioid use skyrocketed in part because of a now-discredited public health campaign that sought to position all pain as a purely physical sensation, a “vital sign” similar to one’s heart rate or blood pressure. Yet research studies are revealing that acute pain may have little in common with chronic pain. If you study the brain using MRI scans or other techniques, these studies show, the phenomenon that chronic pain appears most similar to is memory, and the condition with the most parallels to chronic pain is post-traumatic stress disorder (PTSD).
Pain and memory
The relationship between pain and memory is incredibly close, as many studies have shown, and for good reason. Evolutionarily speaking, pain’s chief purpose is to keep us safe from harm, and to achieve that, it has evolved into an effective teacher. No matter how many times I warn against it, it is only after my daughter touches the hot skillet once that she learns to never do it again.
Because humans are some of the longest-living animals, we need to be able to remember how we got hurt for a very long time. And because our bodies would much rather we be overcautious, our recollections of agony are often exaggerated.
This memory phenomenon, called the peak-end rule, says that we tend to remember an experience through its most emotionally intense points and its end. When it comes to chronic pain, that means the more pain a person lives with, the more likely they are to misremember it as being worse than it was. Even if infrequent, pain’s worst spikes are embedded much more deeply than moments of relative respite; thus our recollection is skewed negatively.
Our ability to memorize is central to the transformation of acute pain into chronic pain. The creation of strong brain connections is required for long-term remembrance, which is what PKMzeta does. This molecule, however, does more than just help us remember the passwords to our online accounts. It is essential to the genesis of chronic pain.
In a landmark experiment, researchers showed that nerve injury increased the levels of PKMzeta in the parts of mouse brains receiving pain signals. These injuries led to the development of chronic pain in the mice, who continued to limp and guard their hurt legs months after the initial injury. Yet when researchers injected ZIP, a substance that blocks the ability of PKMzeta to commit events to memory, the mice no longer developed behaviors characteristic of chronic pain, such as the limping and guarding. As mice lost the ability to remember, they also lost the tendency for acute pain to be learned and recalled as chronic pain.
PKMzeta is primarily present in the hippocampus, the part of the brain devoted to memory and learning. Studies have shown that differences in the shape of the hippocampus among people with back pain can predict which patients have more-exaggerated memories of their pain.
Learn to forget pain
The role of memorization in the development of ceaseless pain leads one to presume that to overcome chronic pain, instead of plying people with opioids or other medications, we might just need to learn how to forget it. There are several instances reported in the medical literature where this is what happened. In one case, a middle-aged architect with long-standing back pain that forced him to take nine pain medications daily and go through additional procedures developed amnesia after a car accident. He not only forgot basic information, such as the names of his doctors, but also lost memory of his chronic pain and his dependence on high-dose opioids. Electroconvulsive therapy used to treat severe depression has also been shown in some cases to treat chronic pain, perhaps through the amnesia that it can induce.
One medication that holds promise for people with chronic pain is propranolol, a drug used for performance anxiety, high blood pressure and tremors, among other uses. It has been shown in clinical trials to weaken the consolidation of negative memories. Propranolol is associated with a reduction in PTSD symptoms in some people and is particularly effective when given to people before they reactivate traumatic memories with a therapist. Intriguing results have been seen with propranolol and chronic pain: Studies suggest it can prevent the development of a hypersensitive pain state among animals and is associated with a reduction of pain in people with arthritis and temporomandibular disorder, a condition that causes pain in the jaw and face.
Other novel interventions that work for patients with PTSD may also work for chronic pain. When soldiers with PTSD look back on their lives or look forward to the future, their visions are dominated by the sights and sounds of war. Similarly, those in persistent pain see their bodies, past and future, racked in pain. Programs that change how PTSD patients remember past events, such as memory specificity training and life review therapy, might also work with patients in an endless vortex of hurt.
Pain is the most common reason people seek medical care, and if it is to be adequately treated, it has to be properly understood. This is particularly crucial at a time when medicine is recovering from a culture of opioid overprescription yet lacks other resources to help those in unremitting agony.
Haider Warraich is a physician at Brigham and Women’s Hospital, VA Boston Healthcare System and Harvard Medical School. He is the author of the just-published book “The Song of Our Scars: The Untold Story of Pain.”