Pain is a subjective experience that feeds on both psychological and emotional elements. We each view and respond to pain differently. This makes pain exceedingly susceptible to placebo responses, and pain is the arena in which the placebo effect has been most extensively researched.
What is the placebo effect and how does it relate to pain?
The placebo effect is a positive effect, created by a drug or treatment that cannot be chalked up to the properties of the placebo itself. It is understood to be due to the patient's belief in a treatment.
In several recent studies, placebos have performed as well as the drugs we spend millions on each year. Interestingly, expensive placebos work better than cheaper ones and placebo injections often are stronger than pill placebos, but surgical placebos often are the most potent. Scientists have known about placebos for decades but traditional healers have used this phenomenon to strengthen their cures for many centuries. Though scientists today go to great lengths (even as far as doing sham “pretend” surgery) to try to neutralize the influence of placebos in order to figure out what outcome is from the actual treatment, it’s not always clear. Many are now trying to figure out how we could actually use the beneficial aspects of the placebo effect to help people who are suffering.
Placebo effect is all about the power of positive thinking—or is it?
Researchers have long assumed that the placebo relies on a patient’s expectations that a drug or treatment will work; several studies have shown that when patients are told they are getting an active medication, they are more likely to experience an improvement in symptoms, even when the therapy is bogus.
However, a new study questions whether the placebo effect is simply about the power of "positive thinking." Instead placebos may be driven by the "ritual" of a treatment—that is, all the pomp and circumstance around the treatment.
This study, published in the journal Pain, was a randomized controlled trial including 97 patients with chronic lower back pain, the vast majority of whom were taking medication. All of the patients were given a 15-minute explanation of the placebo effect and were then randomly assigned to either receive standard care or to receive open-label placebo (OLP) taking one dummy pill twice daily. The pill bottles they received were branded "placebo pills," and the label clearly stated the pills contained microcrystalline cellulose and no active medication.
Both groups of the study were instructed to not alter any of their medications during the study or to make any lifestyle modifications that could affect their pain.
The patients' pain levels and function were evaluated at the beginning of the study and after three weeks. Remarkably, they found that the standard group experienced a 9% decrease in their chronic pain and a 16% reduction in maximum pain. However, those in the open-label placebo group (again they knew they were only getting a placebo pill) enjoyed a 30% reduction in pain, as well as a 29% decrease in pain-related disability.
The investigators concluded that patients may not necessarily need to believe they are receiving an active medication in order for the placebo effect to work.
Dr. Ted Kaptchuk—a professor of medicine at Harvard Medical School, and director of the Program for Placebo Studies and Therapeutic Encounter—speculates that, as opposed to the patients' conscious expectation of an active drug activating the placebo effect, it may be the ritual of receiving the placebo as part of a treatment regimen that stimulates certain regions of the brain to improve symptoms.2
"It's the benefit of being immersed in treatment: interacting with a physician or nurse, taking pills, all the rituals and symbols of our healthcare system," Kaptchuk adds. "The body responds to that."
The neurobiology of placebos
Placebos work through complex neurobiological interactions credited to various mechanisms, such as expectation, emotions, verbal and non-verbal clues, and learned behavior. There are likely different mechanisms because there is not a single placebo effect but rather numerous ones. To date, most of the underlying neurobiological mechanisms have been studied in the context of pain, but other recent placebo research shows an impact on the immune system, motor disorders and depression.
There are several brain regions that receive direct input from nerve fibers carrying pain-related information from the body to the brain. Treatment with a placebo has been found to decrease activity in these "pain centers" in the brain. This seems to work through the placebo's ability to increase levels of natural painkillers known as endorphins, which act to suppress pain. This is also supported by the ability of naloxone, an opioid receptor blocker, to reverse the placebo’s ability to relieve pain. Functional magnetic resonance imaging of the brain has shown that placebo pain relief was obtained via activation of specific areas of the brain and spinal cord.
The brain’s internal "pharmacy" even contains endocannabinoids (similar to chemical THC marijuana) that control things like mood, appetite, and pain. From an evolutionary standpoint, this is all thought to be part of an adaptive mechanism designed to ensure we can extricate ourselves from an acutely dangerous situation before we become overwhelmed and incapacitated with pain.
More and more evidence is pointing to the fact that the stronger we believe in a treatment, the more likely it will work. Neurochemicals seem to be the cause. For example, brain PET scans of Parkinson’s patients light up in the classic dopamine areas when these patients are given L-dopamine tablets. However, the brain PET scans of Parkinson’s patients light up in nearly the exact same way when they are given a placebo and told that there is only a 75% chance that the pill could be L-dopa which triggers dopamine release.
The evolving view of placebos working through neurochemicals is further corroborated by the fact that the three conditions in which placebo effects are most convincing—pain, Parkinson’s disease, and depression—all seem to share mutual brain circuits within the brain.
The December 2016 National Geographic feature story entitled The Healing Power of Faith describes Mike Pauletich's journey, as well as other fascinating real life accounts of everyday people whose lives have been dramatically transformed when they were healed.1 The National Geographic accounts are about healing not by a drug, a surgery, or a medical procedure, but by something else completely. That something, which neuroscientists are learning more and more about, may be as potent as today's strongest medical treatments. It is also ingrained in the DNA of the human nervous system and could help you deal with pain.
Mike Pauletich first noticed some coordination problems and a sore arm. Logically thinking the problem was in his arm – perhaps carpal tunnel syndrome, the 42 year-old technology executive went to see his doctor. After a thorough medical evaluation, the doctors diagnosed him with early onset Parkinson's disease, a progressive neurological illness caused by a deficiency of the brain neurotransmitter dopamine that affects millions of people over the age of 60. Mike, however, was diagnosed much younger. People with Parkinson’s disease often have trouble with movement—involuntary tremors, rigidity, balance, walking—but memory loss and depression are also common symptoms. Currently, there is no known cure. For the next several years after his diagnosis, he struggled not only with his movement and speech but also with related depression.
In 2011 Pauletich heard about a Parkinson's study going on using a novel gene therapy. The therapy sounded pretty aggressive, as it involved cutting two small holes in the skull and injecting a new drug called Neurturin directly into precise areas of the brain. The goal was to increase the amount of dopamine in the brain to alleviate the Parkinson’s symptoms. The treatment had worked in monkeys but was still very experimental in humans. Without any other hopeful treatment options, Pauletich was willing to enroll in the study with the anticipation that he could get better. The study was a double-blind sham-surgery-controlled trial, meaning that neither the patients nor the doctors caring for them would know whether they received the Neurturin injected into their brain or simply receive two divots drilled into their skull without any drug. Along with Pauletich, 50 other people with Parkinson’s were willing to give it a try and enrolled in the study.
Pauletich consented and underwent the brain surgery. Miraculously, afterward, his tremors and slurred speech improved to the point where it is difficult now to tell that he has any problem at all today. His physician, Stanford neurologist Dr. Kathleen Poston (who was also a co-author of the study) was amazed with his improvement. Then in April 2013, the final results of the study were announced and have since been published in the Annals of Neurology. The conclusions of the study: there were no significant improvements in overall Parkinson's symptoms for the patients who received the drug versus those who simply had the holes drilled in their skulls.
Dr. Poston and many hopeful Parkinson's patients were tremendously disappointed and surprised by the negative study results. Then, remembering her patient’s marvelous improvement, Dr. Poston looked closer at the study data and was astonished to discover that Pauletich had not even received the study drug. He was in what was referred to as the “placebo side” of the study and only received the sham surgery, nothing else. How could this be when his improvement was genuine and lasting?
This and the other stories in National Geographic underscore the linkage between how expectations and beliefs impact the effectiveness of treatments. This phenomenon often referred to as the placebo effect can have a powerful impact on both the mind and the body and understanding it has the potential to help people with persistent pain.
As the exact neuroscience of how this all works is being figured out, what is already known suggest that belief and expectation are key parts of our psychological and physical healing. It is likely that Mike Pauletich's response was related not only to the placebo but also to all of the intensive care, specialists, surgery, MRIs, he received, in other words, all of the "rituals" of modern medicine. While he may have only received sham (fake) surgery in the Parkinson's drug study, Mike Pauletich got significant and lasting relief and he said, "Whether it was placebo or some effect of the drug, it doesn't matter to me."
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