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Pain, Placebo, Nocebo and the Brain


Placebos have been used for centuries in medicine, both inside of clinical research studies and out. Interestingly, the word placebo was medically defined in the early 1800s as “any medicine adapted more to please than to benefit the patient.” Although this definition implies deception on the part of the clinician, that isn’t the intent at all today. Thus, the description has been adapted over the years. Placebos are no longer used in treating patients outside of the research setting. However, their clinical research effects remain fascinating and are primarily from where the term “placebo effect” has derived.

A phenomenon studied extensively in medicine and psychology; many people have heard of the “placebo effect” but probably misunderstand it. For most of us, the term placebo refers to some pill or treatment that a patient or clinical study subject believes to be “real”, but in fact, contains no actual medicine or treatment component. When conducting “blind” clinical studies, researchers often hide from subjects whether they are receiving an “active” medication or intervention (being studied to test whether it works and to what extent) or an inactive, placebo treatment (meant to look or appear as if it is an active intervention, but without any expected physiological benefit). Ideally, the active treatment should significantly outperform the placebo. Fascinatingly, subjects who receive a placebo, or no “real” treatment at all, sometimes report improvement in symptoms. Furthermore, sometimes objective evaluation and testing demonstrate improvement. The implication is that the mind is a powerful force that can sometimes heal what might ail our bodies.

I believe this concept and framework for placebo represents only part of the big picture. A more complete and comprehensive understanding requires appreciation of how our brains consistently interpret information, make predictions, and produce an output that it perceives as in our best interest. When receiving a treatment (medication or procedure) we expect to be of benefit, that output is often a physiological response that results in complex changes in our body’s chemistry, resulting in improvement in our condition-what we call placebo. Interestingly, if we expect, anticipate, or fear a negative response the brain can produce physiologic changes that result in poor outcome, side effects and complications- what we call nocebo. Importantly, the most significant factor influencing whether our brain produces physiological responses that are good (placebo) or bad (nocebo) is expectation. The power of expectation tremendously influences our response and outcome. It is both conscious and subconscious. Our minds don’t necessarily trick us into thinking a particular treatment works or doesn’t. And this is not to say that medical treatments and our responses to interventions are completely dependent on expectation. Placebo and Nocebo are simply factors that inform the overall equation of how we respond to treatments. The critical point is that our brains set into motion several complex physiological mechanisms that significantly contribute to benefit, or detriment.

As a neurologist specializing in pain medicine who works with patients daily to help them overcome pain, I know that the brain is perhaps the most potent weapon we have against it. Sometimes, a patient arrives in my office after they have tried just about every powerful and potentially addictive drug under the sun to relieve their constant pain. The first step to overcoming that pain is getting to the bottom of its root cause. Sometimes, the most significant root cause is physical, like a disc herniation compressing a nerve and causing sciatica. But I often point out to patients that many people have disc herniations compressing a nerve but lack sciatic pain. We know that acute herniation is often associated with inflammation. And inflammation can come and go, explaining why an individual’s sciatica pain may come and go despite no physical change in disc herniation or nerve root compression. But there are a number of patients who have chronic, persistent pain in the absence of ongoing inflammation. Current pain science informs us that the brain may be contributing to the chronic pain by misinterpreting electrical signals, reducing the threshold for a pain experience, and inadvertently limiting functional pain-free movement in an effort to protect from its inaccurate perception and prediction of injury (even when no injury or threat of injury exists). The person experiences real pain, but not from tissue damage. The brain produces the pain.

One of my most favorite experiences is helping skeptical patients believe that they have power over their pain. And that power begins in the brain. A first and necessary step is insight and understanding of pain physiology and the power of the brain. Next, is a thorough evaluation of the individual’s history, physical examination, and relevant test results. And finally, giving permission to move, educating on ways to desensitize the nervous system and re-establish a more normal threshold for pain response. Essentially re-training the brain is a powerful tool that augments the benefits of medications, injections, neuromodulation, rehabilitation, and other pain management techniques. But to harness it takes practice. Mindfulness meditation, cognitive behavioral therapy, and other brain training options are absolute difference-makers for people who live with constant pain. All pain, no matter where it is felt in the body, begins in the brain. So, the brain is where we can often start to help heal or minimize the pain.

As a neurologist, now is a great time to be practicing medicine because more and more research shows us the benefits of training the brain against pain – without the use of powerful drugs to do it. The placebo effect isn’t evidence of the ability to “dupe” the brain, in my opinion. Instead, it illuminates just how powerful the brain can be in healing the body.