Placebo and nocebo in the treatment of back pain

Placebo

I Patrick D. Wall, describing the placebo response in the pain guide, writes that the word "placebo" is mentioned in Psalm 116: 9: "Placebo Domo in the regione vivorum" in the first line of the evening memorial prayer (in the Church Slavonic translation " in the land of the living "). Priests and monks did not give people peace, forcing them to order an evening prayer for money. Placebo was an expression of contempt for unpopular and costly prayers, as Francis Bacon wrote in 1625, "Sing to him the placebo song instead of letting go of your sins." Three years later, Burton writes in Anatomy of Melancholia, "often healers, or a stupid surgeon, achieved more strange cases of recovery than a reasonable therapist, since the patient trusted them more." Now, more than four hundred years later, the placebo response is still used in medicine and the mechanism of this phenomenon is becoming more understandable.

Placebo is a physiologically inert substance used as a medicine, a positive therapeutic effect is due to unconscious psychological expectation of the patient. In addition, the term "placebo effect" refers to the phenomenon of non-drug exposure itself, not just the drug, but, for example, radiation (sometimes using different "flashing" devices, "laser therapy"), etc. Lactose is often used as a substance for placebo. The degree of manifestation of the placebo effect depends on the suggestibility of the person and the external circumstances of the "treatment", for example, on the size and brightness of the color of the pill, the degree of confidence in the doctor, the authority of the clinic.

Henry Beecher, the first head of the anesthesiology department at the Massachusetts Multipurpose Hospital, published his classic "Power of placebo" in 1955. In it, he suggested that the patient's expectation of benefit was sufficient to achieve a therapeutic effect. He also suggested that the general analgesic effect of morphine is composed of its drug effect and placebo effect. About fifty years later, with the help of modern technologies, scientific research could provide confirmation of the hypothesis of G. Bicher and prove the neurobiological mechanism of this phenomenon. Modern studies have also shown that the placebo effect is far from a miracle. Depending on the conditions, the placebo effect can be narrowly directed and have a somatopic organization.

The mechanism of placebo analgesia is considered from several positions. Cognitive theory asserts that patient expectations play an important role in the placebo response. Patient expectations are the best predictor of outcome in pain management. It is suggested that placebo analgesia may be partially mediated by endogenous opioids, since the effect may be inhibited by the opioid naloxone antagonist. It has been suggested that waiting for pain relief can trigger the release of endogenous opioids in the central nervous system. The conditional theory states that in the placebo-response it is important to study associative connections. This theory suggests that a placebo-response is a conditional response to a stimulus that causes the relief of symptoms and leads to an improvement in physical condition. It is assumed that there is a similarity to the classical conditioned reflex described by I. Pavlov in dogs. He presented a report about dogs that had been injected with morphine in a certain chamber and showed a morphine effect when they were again placed in the same chamber, despite the fact that morphine was not injected into them. Repeated associations between active analgesics, pain relief and the therapeutic environment can produce a conditional analgesic placebo response. As stated above, endogenous opioids may be at least partially responsible for placebo analgesia, since the opioid antagonist naloxone is capable of canceling placebo analgesia. Amanzio and Benedetti, using the experimental model of human ischemic pain, caused a placebo anesthetic response with the use of "dummy", drugs (morphine or ketorol) and their combination. The dummies produced a placebo effect that was completely blocked by the opioid antagonist naloxone. The combined use of pacifier and morphine also caused a placebo effect completely leveled by naloxone. The use of morphine without a pacifier caused a naloxone-reversible placebo effect. However, the placebo effect caused by the intake of ketorol and the dummy was only leveled by naloxone. The use of ketorol without a pacifier caused a placebo response that was not sensitive to naloxone. The authors concluded that waiting triggers the release of endogenous opioids, while measures to improve the physical state activate specific subsystems.

Studies using positron emission tomography showed that the opioid analgesic and placebo activated the same neural structures, including the rostral part of the anterior cingulate gyrus of the cerebral cortex, the prefrontal cortex and the brain stem, that is, the areas involved in the pain modulation process. The study also suggested that the variation of the placebo response in different people may be due to the individual ability to activate this system. Interestingly, those who had a good placebo effect during the analgesia with remifentanil showed stronger activation of this system.

It was suggested that the mediator in the placebo-associated effect could be dopamine. The study of patients with Parkinson's disease with PET and swab-labeled raclopride showed that a placebo-induced release of endogenous dopamine is associated with a weakening of symptoms. The magnitude of the dopamine response in the placebo effect was comparable to the therapeutic dose of levodopa.

In 1999, Benedetti and co-authors further investigated the role of the opioid system in the targeted waiting for analgesia. They stimulated the feet and brushes with subcutaneous administration of capsaicin. The specific expectation of analgesia was caused by applying a placebo, cream to one of these parts of the body, while the subject was told that this is a strong local anesthetic. The results showed that a highly somatotopically organized system of endogenous opioids combined the expectation, attention and body design.

A placebo response can be enhanced by a good doctor-patient interaction. Expectations of the therapist and the patient's sense of this hope also contribute to the manifestation of a placebo effect.

Nocebo

Often, patients from the placebo treatment unit report side effects similar to those found in the actual treatment unit. Such adverse placebo effects have been termed nocebo effects. The cognitive and conditional mechanisms triggering the nocebo-response are the same as in the placebo-response. It is very important to take this into account when developing a clinical research plan. Informing patients and leading questions about adverse effects may affect the results. Also important is that patients often experience symptoms such as fatigue, increased sweating, constipation at baseline, even before the test. To reinforce the patient's real ignorance, an active placebo is sometimes used. An active placebo imitates the drug under study, causing adverse effects without exerting a specific effect on the underlying manifestations of the disease.

Placebo effect in the clinic

Studies show that placebo analgesia has a neurophysiological basis and that different individuals exhibit a wide range of placebo responses. Therefore, it becomes apparent that a placebo can not be used to determine if the patient is experiencing pain truly or not. Medicinal placebo drugs can not be used as an alternative to analgesics. However, the mechanisms of action of placebo analgesia, which have been disclosed, especially when physician-patient interaction, can be used to improve the effectiveness of treatment. The importance of the doctor-patient interaction was recognized constantly, but only now its neurobiological basis became more understandable. If those who care for the patient used effective methods in which they believe, and if they transferred this confidence to the patient, their treatment would be more effective than the same, conducted by skeptics.