Placebo Analgesia
If Placebo Analgesia Works, What Does It Tell Us About the Nature of Pain?
Pain appears to be one of the most direct experiences we possess. Touching a hot stove or breaking a bone produces an immediate sensation of pain, reinforcing the long-standing biomedical assumption that pain is a direct result of tissue damage and an accurate indicator of bodily injury. However, placebo analgesia challenges this assumption.
Placebo analgesia is defined as the phenomenon whereby “an individual experiences a real reduction in pain after receiving an inactive treatment.” If inert treatments can reduce genuine pain, then pain must not simply be a product of the body's sensory nervous system's response to harmful stimuli (nociception). Instead, it raises the possibility that pain is not merely detected by the brain but actively interpreted by it. Understanding why placebo analgesia occurs may therefore reveal not only how pain can be treated, but what pain fundamentally is.
Contemporary theories describe pain as an experience that arises from the interaction of various biological, psychological, and social factors. The International Association for the Study of Pain (IASP) defines pain as “an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage” [1], a definition widely accepted by healthcare professionals and researchers in the field of pain research. This revised definition recognises that pain is also shaped by cognitive factors such as attention, prior experience, and expectations, rather than existing as a direct consequence of tissue damage. It emerges as an interpretive experience, reflecting both what is happening to the body biologically and the meaning the brain assigns to those signals. If pain depends partly on interpretation then placebo analgesia is no longer a paradox but an expected consequence of the way it is felt. Perhaps the most powerful implication is that changing how pain is interpreted may itself alter how it is experienced, challenging the idea that effective relief must always begin by targeting the physical damage.
A 2024 randomised clinical trial [2] investigated the effects of openly prescribed placebo (saline solution) injections in 101 adult patients with chronic back pain. The patients receiving the placebo reported significantly greater reductions in pain intensity after 1 month, as well as improvements in mood and sleep quality, despite knowing they had not received any active medication. Functional MRI scans revealed changes in brain regions involved in pain regulation, including increased activity within the medial prefrontal cortex, a region involved in regulating pain. This is supported by earlier research showing that taking a placebo may activate the body’s own natural opioid system, causing the release of endorphins which are similar to those produced when actual opioid medications are taken. If a placebo can alter both subjective and measurable pain without deception then the experience of pain appears to also depend in part on how the brain interprets and responds to treatment. Rather than exposing a weakness in human perception, these findings suggest the brain’s capacity to modulate hurting, may offer a valuable therapeutic opportunity.
In 2022, a Pain Reprocessing Therapy (PRT) trial taught patients to reinterpret their chronic back pain as arising from non-dangerous processes rather than ongoing tissue damage [3]. The therapy aimed to reduce the perceived threat associated with pain. 151 adults with chronic back pain were randomly assigned to PRT (n = 50), an open-label placebo (n = 51) and usual care (n = 50). After four weeks, 66% of the PRT group were pain-free or nearly pain-free (pain score 0-1/10) compared with 20% in the placebo group and 10% in the usual care group, improvements which persisted for at least one year. Whilst these results show that the mind can influence the body, the two are difficult to meaningfully separate in the experience of pain. This is not limited to conditions where the source of pain is uncertain, such as chronic back pain, but has also been observed in patients with cancer. A meta-analysis of 37 randomised controlled trials involving 4,199 patients found that, despite having no effect on the underlying disease, psychosocial interventions such as cognitive behavioural therapy (CBT) and relaxation training significantly reduced reported pain severity [4]. Disease may explain why pain occurs, but it does not entirely determine how pain is experienced; and this may be why two individuals who share the same pathology may experience profoundly different levels of pain.
The important question is, why do some individuals seem naturally more aware of pain than others? For example, being able to continue on with their day as normal when experiencing an awful headache. Current evidence suggests that this is shaped by both genetic predisposition and experience, as is often the case in biopsychology. Genetic differences may influence how sensitive individuals are to pain whilst repeated experiences of pain may also change the way the brain processes it. Research has shown that as pain becomes chronic, brain activity gradually shifts from areas involved in processing physical pain to regions associated with emotion and motivation [5]. This suggests that it is not a fixed experience but one that develops over time. Perhaps, then, pain-tolerance is not simply about enduring more pain, but about how the brain learns to interpret and prioritise the signals it receives challenging the notion that pain-tolerance is a fixed physical trait reflecting an ability to endure pain. Rather, it may reflect the brain’s ability to regulate the importance it assigns to the sensation of pain.
Ultimately, placebo analgesia reveals that pain is far more than a measure of tissue damage. It is a dynamic experience, continually shaped by biology, psychology and the meaning we assign to our bodily sensations. Whilst pain may not be “all in the mind”, that mind is part of the biology itself. If our past experiences, expectations and relationships can influence how pain is experienced then we are not simply passive recipients of pain. We may have more capacity to shape our experience of it; at least more than we once believed.
[1] https://pubmed.ncbi.nlm.nih.gov/32694387/
[2] https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2823541
[3] https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2784694