“Pain is the product of bottom-up processes and top-down modulation.”
(Dr Fabrizio Benedetti)
In this post, I will be considering the nature of the connection between inflammation, the placebo effect, and how talking therapy could be used to enhance placebos. We are self-healing beings, evolution has imbued us with this capacity and we should look to create an environment that helps support this capacity. Although placebo is recognised by many as an effective form of treatment it is not directly pursued within a therapeutic setting. The question is should it be and if it should, how best to invoke placebo to maximum effect?
Placebos are now a well-recognised phenomenon within the scientific community and consequently is often considered in the design in many clinical trials. The numerous studies carried out with regards to placebo now indicate its particular effectiveness when dealing with inflammatory related conditions such as pain, swelling, depression, anxiety, and even stomach ulcers. Placebo does affect positive visible tissue change, but at the same time is largely a subjective experience. As a subjective experience, the presence of such an effect indicates that it is very much mediated by psychological input. Consequently, we can therefore assume that talking therapy could be used as a useful adjunct alongside other forms of pain and inflammatory management therapies.
So what are placebos?
The literal meaning of placebo in Latin is ‘I will please’, this intimates that placebo was originally seen as some sort of no-entity, deception or even trickery to keep people happy. The word ‘Placebo’ today commonly refers to an inert drug or treatment and the placebo effect is seen as a change in the condition as a consequence of the inert drug or treatment. A positive change as a consequence of an inert intervention is not magic; it is simply a readjustment of the body’s own natural healing mechanisms to a change in perception. Perceptual change is a result of a change in the individual's hopes and beliefs towards positive change. Our sense of hopes and beliefs are intimately tied to awareness, becoming more conscious and aware of what is working can go a long way towards maximising placebo. With this in mind possibly a more accurate term for placebo effect would be ‘hope effect’, ‘belief effect’, or ‘awareness effect’.
Conditioning of the immune system
Behaviourists originally developed a model of human behaviour that was based on an oversimplified ‘stimulus to response’ approach. Unfortunately, this model gave little consideration to the influence of hopes, beliefs and desires in the role of human behaviour. A more accurate model therefore would be one that recognises these psychological factors, thereby developing this model to now include ‘conditioning’, to read ‘stimulus-conditioning-response’.
Conditioning is not limited just to externally observable behaviour but it can also extend to the actions of the immune system. This has been proven time and time again in a number of different studies. One such example involved the conditioning of an inflammatory response to gentle scratching of Guinea Pigs. In this study guinea pigs were repeatedly exposed to a neural stimulus in this case gentle scratching just before being injected with a substance that triggered an inflammatory response. After a number of repetitions of the same cycle, the guinea pigs' immune system learned to associate scratching with inflammation. This association became so strong (conditioned) that eventually, gentle scratching on its own was enough to provoke symptoms of inflammation such as swelling and redness.
Another such example was a study in which a placebo ‘pain killing’ medication was given along with an inert ‘special drink’, when the ‘special drink’ was replaced by just water the reported effect of the placebo medication diminished. Effectively the inert ‘special drink’ produced a positive conditioned response. From these two studies and many other similar studies we can conclude that if an ‘unconditioned stimulus’ is repeatedly paired with a ‘conditioned stimulus', eventually a ‘conditioned response’ will be learnt.
The psychology of inflammation
The key to understanding placebo response lies in understanding how the mind (the physical process of the brain and nervous system) can appropriately manage inflammation. Like pain, inflammation is an important and necessary part of any healing process. An immune response can be divided into two responses; that of the innate response and the acquired response.
The innate response is activated in the early stages of infection or injury, this is the inflammatory response and is characterised by physical signs such as redness, swelling, heat, pain. Along with these physical signs, there are also psychological signs, these include lethargy, apathy, loss of appetite, and increased sensitivity to pain. These suites of symptoms related to the psychological effects are referred to as ‘sickness behaviour’. Both changes although unpleasant are necessary, in fact, the unpleasant feelings experienced are a vital part of their function.
The innate response only takes minutes to activate and in normal circumstances can last for several days or until sufficient time has passed for the acquired immune system (immunity you acquire during your life) to build up its forces so it can now deal with the threat. The acquired immune system is made up of T-Lymphocytes, B-Lymphocytes, and Antibodies. Their role is to destroy any invading pathogen and any toxic molecules they produce. This whole process is the actions of a number of chemical messengers and how the brain utilises these to exert downward control over pain and inflammatory response. There are a large number of chemical processes involved in the whole inflammatory process but I will just discuss just a few that I feel are important to our understanding for now.
The pain and inflammatory actions of endorphins have been identified in a number of studies, in one such study they looked at the influence of endorphins on postoperative pain. To do this they used a drug called Naloxone which blocks the receptor sites that endorphins attach to. The outcome of the study was that those participants who were given Naloxone experienced more inflammation and pain, intimidating the importance of endorphins in the healing process.
Another such chemical worth looking into is the actions of the neurotransmitter (chemical for communication) dopamine. Dopamine creates pleasure from the expectation of reward and is released by the nucleus accumben which is located in the basal forebrain. Dopamine has been studied extensively in relation to many actions but in particular motivation. As motivation is intertwined with emotions such as hope and belief it also consequently plays a significant role in the placebo effect.
Two other components worth considering are the actions of interleukin and cortisol. Both are involved in the inflammatory response so are both parts of the immune response. Interleukin is a protein released by the cells to promote inflammation but it also triggers the hypothalamic-pituitary-adrenal axis (HPA axis) to release cortisol. It appears that the interleukin and cortisol work together to promote healing initially through the inflammatory action of interleukin and laterally through the action of cortisol via its dampening down effects of inflammation. Interestingly enough it has been noted that high levels of both interleukin and cortisol have been found in individuals suffering from depression.
The relationship between mind and body is indisputable, the actions of the immune system and psychological state have been proven in study-after-study. The actions of the placebo effect are mediated through chemical changes (within the nervous system) as a consequence of a change in perception and awareness. This understanding, therefore, opens the door for managing pain and inflammation by maximising the placebo effect through the use of talking therapy.
Managing pain through the use of talking therapy
Depression and anxiety have been clearly linked to biochemical disruption of normal inflammatory response. It is also quite clear by now that placebos (particularly with regards to pain and inflammation) could be used as a form of treatment. As the effects of placebo are a consequence of a change in perception, would it not be logical to assume that interventions that aid in supporting individuals to shift perception would be worth exploring?
Talking therapies such as Solution Focused Therapy could be incorporated into a pain management treatment plan, either on its own or as an adjunct with other forms of therapy such as physiotherapy, osteopathy, chiropractic, etc. As an adjunct, it could improve outcomes by ‘preloading’ the patient with good expectations and anticipation of being healed even before seeing their manual therapist. It could also have a place In a more long term care setting by supporting treatment adherence and motivation.
Talking therapy could also lead to giving the patient a greater sense of autonomy and self-efficacy. By moving the patient from a passive participant (who is reliant on the expertise of their practitioners) to an active participant who is actively involved in healing themselves. Just this shift could see self-confidence grow and as confidence is grounded in belief and as belief is central to the powerful engagement of placebo then developing patient confidence would warrant exploring.
Talking therapies could also be used as a means of instilling the patient with a greater sense of hope. Hope is a key determinant in improving treatment outcomes. It has been shown that patients with a greater sense of hope can tolerate pain for longer and adjust better to managing pain. Hopelessness in contrast has been linked to depression, as it implies a negative expectation of the future. Hopelessness also negatively impacts the patient sense efficacy by lowering the individuals' impression of their own capabilities.
We fight disease in many different ways and have evolved both innate and acquired means of doing so. The power of the mind to heal the body must always be considered and although it may not be unlimited in its capacity in doing so, it can and does play an important role. As we have seen, the engendering of self-belief, hope, and possibility can result in real physiological change, improving patient outcomes and well-being. We have also seen that the power of the placebo effect is real and significant. I, therefore, subscribe to the belief that all forms of therapy that deal with pain management should utilise ways and means to enhance placebo. In fact, it could well be that therapists that are classified as ‘good pain management therapists’, may (intentionally or otherwise) just excel at the art of evoking the placebo effect.