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The influence of verbal suggestions in the management of musculoskeletal pain: a narrative review
Abstract
Background: Pain has been considered to be the most disabling symptom of musculoskeletal disorders. It is the cause of a large number of medical consultations and high health costs around the world. Chronic back pain affects a larger population than other types of pain, with observed prevalence of between 53% and 81%; this has economic, clinical and social repercussions for the health system.
Objective: The purpose of the present article is to describe the utility and the neurobiological mechanisms of verbal suggestion as a therapeutic ally during the management of patients with musculoskeletal pain.
Important discoveries: Inducing expectations by means of verbal suggestions can activate placebo or nocebo pathways when the clinical professional uses either positive or negative words respectively. When the administration of drugs and physiotherapy interventions are accompanied by words which induce positive expectations, this may improve certain clinical parameters such as pain and/or function in people suffering low back pain. Equally important, the use of positive verbal suggestion may decrease the perception of pain in patients with osteoarthritis.
Conclusions: In the management of clinical musculoskeletal pain, the inclusion of verbal suggestion has the potential to induce expectations which may generate hypoalgesia through the placebo effect; however, more research is needed to determine the magnitude and clinical significance of this contribution.
Keywords: Musculoskeletal pain, verbal suggestion, expectations, placebo effect
... In particular, these expectation interventions are triggering placebo effects where expectancy is known to be a core mechanism. [2,3] Verbal suggestion is a communication process that conveys information about certain concepts to others and thereby provokes beliefs, expectations, thoughts, emotions, behaviors, or physical states in them consciously or unconsciously [4] . It is known to be a potential therapeutic element which influences the treatment outcomes in the patients who are suffering with pain [4] and the effect of it in pain relief is more frequently studied in literature. ...
... [2,3] Verbal suggestion is a communication process that conveys information about certain concepts to others and thereby provokes beliefs, expectations, thoughts, emotions, behaviors, or physical states in them consciously or unconsciously [4] . It is known to be a potential therapeutic element which influences the treatment outcomes in the patients who are suffering with pain [4] and the effect of it in pain relief is more frequently studied in literature. This is identified as a concept which alters the patient's perception regarding the pain through hypnotic process. ...
... The verbal suggestion is a communication process that conveys information about certain concepts to others and thereby provokes beliefs, expectations, thoughts, emotions, behaviors, or physical states in them consciously or unconsciously (Cuyul-Vásquez et al., 2019). It is a contextual factor that influences the therapeutic outcome by triggering placebo or nocebo effects (Wager and Atlas, 2015). ...
... Additionally, oxytocin (Enckand Klosterhalfen, 2009;Kessner et al., 2013), nitric oxide (Fricchione and Stefano, 2005), and cholecystokinin (Benedetti et al., 2006) are also suggested to be contributing to the placebo response. When verbal suggestions are used to induce positive expectations towards the therapeutic outcomes, it is known to be augmenting the activity of opioids and dopaminergic systems (Cuyul-Vásquez et al., 2019). Increased dopaminergic activity is found in the nucleus accumbens during the process of verbal suggestion (Rossettini et al., 2018;Morral et al., 2017). ...
... Another shortcoming in our study was the lack of control of contextual factors (e.g. level of therapeutic alliance, patient's expectations, verbal suggestions, therapist's expertise, and belief) during the delivery of interventions which have been acknowledged as central to treatment responsiveness (Cuyul-Vásquez, Barría, Perez, and Fuentes, 2019;Fuentes et al., 2014). Also, the type of rupture and surgery, beliefs, expectations of recovery and presence of central sensitization were not considered as confounding variables. ...
Objective:
To compare the effectiveness of pain neuroscience education (PNE) versus biomedical education (BME) in a rehabilitation program following arthroscopic rotator cuff repair (ARCR) in patients with chronic shoulder pain.
Methods:
Twenty-nine patients who participated in a rehabilitation program were randomly assigned to either an experimental PNE group (N = 16) or a control BME group (N = 13). Measurements included pain intensity at rest and in movement, pain catastrophizing, kinesiophobia, disability and health-related quality of life (HRQoL). Outcomes were evaluated at baseline and at 4 and 8 weeks after the intervention.
Results:
A main effect for time was observed for: intensity of pain at rest (p < .01); pain with movement (p < .01); pain catastrophizing (p < .01); kinesiophobia (p < .01); disability (p < .01); and HRQoL (p < .01). No group interactions were significant for any variable, except for pain with movement, which favored the PNE group (p = .03). Large effect sizes (ranging from d = 0.79 to d = 2.65) were found for both interventions in all outcomes.
Conclusion:
A rehabilitation program including either PNE or BME are equally effective in improving rest pain, pain catastrophizing, kinesiophobia, disability, and HRQoL in patients after ARCR, except for pain at movement in favor of the PNE group. The inclusion of PNE in the rehabilitation program appears to lead to clinically meaningful improvements in pain at rest in short term when treating patients with ARCR.
... The PUP and the OLP closely match in design and treatment duration, except OLP participants were explicitly instructed about the power of placebo. These positive instructions seems to have increased the effect size in OLP by 4 times that of PUP, consistent with evidence that instructions induce large hypoalgesic effects [6,11,18,23]. ...
The objective of this study is to validate a placebo pill response predictive model - a biosignature - that classifies chronic pain patients into placebo-responders (predicted-PTxResp) and non-responders (predicted-PTxNonR), and test whether it can dissociate placebo and active treatment responses. The model, based on psychological and brain functional connectivity, was derived in our previous study and blindly applied to current trial participants. 94 chronic low back pain (CLBP) patients were classified into predicted-PTxResp or predicted-PTxNonR and randomized into no-treatment, placebo treatment, or naproxen treatment. To monitor analgesia, back pain intensity was collected twice a day: 3 weeks baseline, 6 weeks of treatment, 3 weeks of washout. 89 CLBP patients were included in the intent-to-treat analyses and 77 CLBP in the per-protocol analyses. Both analyses showed similar results. At the group level, the predictive model performed remarkably well, dissociating the separate effect sizes of pure placebo response and pure active treatment response, and demonstrating that these effects interacted additively. Pain relief was about 15% stronger in the predicted-PTxResp compared to the predicted-PTxNonR receiving either placebo or naproxen, and the predicted-PTxNonR successfully isolated the active drug effect. At a single subject level, the biosignature better predicted placebo non-responders, with poor accuracy. One component of the biosignature (dorsolateral prefrontal cortex-precentral gyrus functional connectivity) could be generalized across three placebo studies and in two different cohorts - CLBP and osteoarthritis pain patients. This study shows that a biosignature can predict placebo response at a group level in the setting of a randomized controlled trial.
... The manipulation of verbal and non-verbal aspects of communication was carried out according to the objective of each of the three intervention sessions: (1) Establish a bond and prescribe exercise; (2) Explain the mechanisms of action of exercise; (3) Reinforce the prescription and the mechanisms of action of the exercise. Also, the use of positive verbal suggestion during the explanation of the effects of the therapeutic exercise protocol was avoided in the scripts, because it has been observed to promote expectations that may influence treatment outcomes 26 . ...
Background
Previous evidence has shown that seniors physical therapists applying electrotherapy and an enhanced therapeutic alliance in their sessions can positively influence the levels of analgesia of patients with chronic low back pain. It is currently unknown if these effects can be achieved in people with symptomatic knee osteoarthritis when receiving treatment focused on therapeutic exercise.
Aim
To determine the effects of different therapeutic alliance levels during the application of a therapeutic exercise program on pain intensity and pressure pain threshold in patients with symptomatic knee osteoarthritis.
Method
This will be a randomized, parallel, two-arm, clinical trial. An intervention of three sessions of therapeutic exercise will be applied for one week. Patients aged 45 to 65 years old with a clinical and radiographic diagnosis of knee osteoarthritis will participate. Also, patients with a pain intensity of at least three months duration and 3 to 8 points in a numerical rating scale will be included. Patients will be randomly assigned to a therapeutic exercise experimental group with an enhanced therapeutic alliance (e.g., active listening, personalized conversation, empathy) or limited therapeutic alliance (e.g., one-way verbalization, brief interaction). Physical therapists will be trained in delivering these two levels of the therapeutic alliance. The pressure pain thresholds at the symptomatic knee and the pain intensity will be measured before and after the intervention.
Discussion
The results of this research will determine the impact of the therapeutic alliance as a nonspecific relevant factor during the application of a therapeutic exercise program in the treatment of patients with symptomatic knee osteoarthritis.
Clinical trials registration number
NCT04390932
Placebo and nocebo effects are intriguing phenomena in pain perception with important implications for clinical research and practice because they can alleviate or increase pain. According to current theoretical accounts, these effects can be shaped by verbal suggestions, social observational learning, and classical conditioning and are necessarily mediated by explicit expectation. In this review, we focus on the contribution of conditioning in the induction of placebo hypoalgesia and nocebo hyperalgesia and present accumulating evidence that conditioning independent from explicit expectation can cause these effects. Especially studies using subliminal stimulus presentation and implicit conditioning (i.e., without contingency awareness) that bypass the development of explicit expectation suggest that conditioning without explicit expectation can lead to placebo and nocebo effects in pain perception. Because only few studies have investigated clinical samples, the picture seems less clear when it comes to patient populations with chronic pain. However, conditioning appears to be a promising means to optimize treatment. In order to get a better insight into the mechanisms of placebo and nocebo effects in pain and the possible benefits of conditioning compared to explicit expectation, future studies should carefully distinguish both methods of induction.
Placebo and nocebo effects are embodied psycho-neurobiological responses capable of modulating pain and producing changes at different neurobiological, body at perceptual and cognitive levels. These modifications are triggered by different contextual factors (CFs) presented in the therapeutic encounter between patient and healthcare providers, such as healing rituals and signs. The CFs directly impact on the quality of the therapeutic outcome: a positive context, that is a context characterized by the presence of positive CFs, can reduce pain by producing placebo effects, while a negative context, characterized by the presence of negative CFs, can aggravate pain by creating nocebo effects. Despite the increasing interest about this topic; the detailed study of CFs as triggers of placebo and nocebo effects is still lacked in the management of musculoskeletal pain.
Increasing evidence suggest a relevant role of CFs in musculoskeletal pain management. CFs are a complex sets of internal, external or relational elements encompassing: patient’s expectation, history, baseline characteristics; clinician’s behavior, belief, verbal suggestions and therapeutic touch; positive therapeutic encounter, patient-centered approach and social learning; overt therapy, posology of intervention, modality of treatment administration; marketing features of treatment and health care setting. Different explanatory models such as classical conditioning and expectancy can explain how CFs trigger placebo and nocebo effects. CFs act through specific neural networks and neurotransmitters that were described as mediators of placebo and nocebo effects.
Available findings suggest a relevant clinical role and impact of CFs. They should be integrated in the clinical reasoning to increase the number of treatment solutions, boosts their efficacy and improve the quality of the decision-making. From a clinical perspective, the mindful manipulation of CFs represents a useful opportunity to enrich a well-established therapy in therapeutic setting within the ethical border. From a translational perspective, there is a strong need of research studies on CFs close to routine and real-world clinical practice in order to underline the uncertainty of therapy action and help clinicians to implement knowledge in daily practice.
Nocebo effects, i.e., adverse treatment effects which are induced by patients’ expectations, are known to contribute to the experience of physical symptoms such as pain and itch. A better understanding of how to minimize nocebo responses might eventually contribute to enhanced treatment effects. However, little is known about how to reduce nocebo effects. In the current randomized controlled study, we tested whether nocebo effects can be minimized by positive expectation induction with respect to electrical and histaminic itch stimuli. First, negative expectations about electrical itch stimuli were induced by verbal suggestion and conditioning (part 1: induction of nocebo effect). Second, participants were randomized to either the experimental group or one of the control groups (part 2: reversing nocebo effect). In the experimental group, positive expectations were induced by conditioning with verbal suggestion. In the control groups either the negative expectation induction was continued or an extinction procedure was applied. Afterwards, a histamine application test was conducted. Positive expectation induction resulted in a significantly smaller nocebo effect in comparison with both control groups. Mean change itch NRS scores showed that the nocebo effect was even reversed, indicating a placebo effect. Comparable effects were also found for histamine application. This study is the first to demonstrate that nocebo effects can be minimized and even reversed by conditioning with verbal suggestion. The results of the current study indicate that learning via counterconditioning and verbal suggestion represents a promising strategy for diminishing nocebo responses.
Background
Chronic pain is a major economic and social health problem. Up to 79% of chronic pain patients are unsatisfied with their pain management. Meeting patients’ expectations is likely to produce greater satisfaction with care. The challenge is to explore patients’ genuine expectations and needs. However, the term expectation encompasses several concepts and may concern different aspects of health‐care provision.
Objective
This review aimed to systematically collect information on types and subject of patients’ expectations for chronic pain management.
Search strategy
We searched for quantitative and qualitative studies. Because of the multidimensional character of the term “expectations,” the search included subject headings and free text words related to the concept of expectations.
Data extraction and synthesis
A framework for understanding patients’ expectations was used to map types of expectations within structure, process or outcome of health care.
Main results
Twenty‐three research papers met the inclusion criteria: 18 quantitative and five qualitative. This review found that assessment of patients’ expectations for treatment is mostly limited to outcome expectations (all 18 quantitative papers and four qualitative papers). Patients generally have high expectations regarding pain reduction after treatment, but expectations were higher when expressed as an ideal expectation (81‐93% relief) than as a predicted expectation (44‐64%).
Discussion and conclusions
For health‐care providers, for pain management and for pain research purposes, the awareness that patients express different types of expectations is important. For shared decision making in clinical practice, it is important that predicted expectations of the patient are known to the treating physician and discussed.
Structure and process expectations are under‐represented in our findings. However, exploring and meeting patients’ expectations regarding structure, process and outcome aspects of pain management may increase patient satisfaction.
The study investigated whether typical psychological, physiological, and neurophysiological changes from a single exercise are affected by one’s beliefs and expectations. Seventy-six participants were randomly assigned to four groups and saw different multimedia presentations suggesting that the subsequent exercise (moderate 30 min cycling) would result in more or less health benefits (induced expectations). Additionally, we assessed habitual expectations reflecting previous experience and beliefs regarding exercise benefits. Participants with more positive habitual expectations consistently demonstrated both greater psychological benefits (more enjoyment, mood increase, and anxiety reduction) and greater increase of alpha-2 power, assessed with electroencephalography. Manipulating participants’ expectations also resulted in largely greater increases of alpha-2 power, but not in more psychological exercise benefits. On the physiological level, participants decreased their blood pressure after exercising, but this was independent of their expectations. These results indicate that habitual expectations in particular affect exercise-induced psychological and neurophysiological changes in a self-fulfilling manner.
Aims
To examine how the choice of words explaining ultrasound (US) may influence the outcome of physiotherapy treatment for low back pain (LBP).
Methods
Sixty-seven patients with LBP < 3 months were randomly allocated to one of three groups – traditional education about US (control group [CG]), inflated education about US (experimental group [EG]) or extra-inflated education about US (extra-experimental group [EEG]). Each patient received the exact same application of US that has shown clinical efficacy for LBP (1.5 Watts/cm² for 10 minutes at 1 Megahertz, pulsed 20% over a 20 cm² area), but received different explanations (CG, EG or EEG). Before and immediately after US, measurements of LBP and leg pain (numeric rating scale), lumbar flexion (distance to floor) and straight leg raise (SLR) (inclinometer) were taken. Statistical analysis consisted of mixed-factorial analyses of variance and chi-square analyses to measure differences between the three groups, as well as meeting or exceeding minimal detectable changes (MDCs) for pain, lumbar flexion and SLR.
Results
Both EG and EEG groups showed a statistically significant improvement for SLR (p < 0.0001), while the CG did not. The EEG group participants were 4.4 times (95% confidence interval: 1.1 to 17.5) more likely to improve beyond the MDC than the CG. No significant differences were found between the groups for LBP, leg pain or lumbar flexion.
Conclusion
The choice of words when applying a treatment in physiotherapy can alter the efficacy of the treatment.
Patients' expectations are important predictors of the outcome of analgesic treatments, as demonstrated predominantly in research on placebo effects. Three commonly investigated interventions that have been found to induce expectations (verbal suggestion, conditioning, and mental imagery) entail promising, brief, and easy to implement adjunctive procedures for optimizing the effectiveness of analgesic treatments. However, evidence for their efficacy stems mostly from research on experimentally evoked pain in healthy samples, and these findings might not be directly transferable to clinical populations. The current meta-analysis investigated the effects of these expectation inductions on patients' pain relief. Five bibliographic databases were systematically searched for studies that assessed the effects of brief verbal suggestion, conditioning, or imagery interventions on pain in clinical populations, with patients experiencing experimental, acute procedural, or chronic pain, compared to no treatment or control treatment. Of the 15955 studies retrieved, 30 met inclusion criteria, of which 27 provided sufficient data for quantitative analyses. Overall a medium sized effect of the interventions on patients' pain relief was observed (Hedges's g = 0.61, I2 = 73%), with varying effects of verbal suggestion (k = 18, g = 0.75), conditioning (always paired with verbal suggestion, k = 3, g = 0.65), and imagery (k = 6, g = 0.27). Subset analyses indicated medium to large effects on experimental and acute procedural pain, and small effects on chronic pain. In conclusion, patients' pain can be relieved with expectation interventions, particularly verbal suggestion for acute procedural pain was found to be effective.
See for full text: http://journals.lww.com/pain/Abstract/2016/06000/Relieving_patients__pain_with_expectation.2.aspx
Objective:
A prior knee osteoarthritis (OA) trial found that provider conveyed expectations for treatment success were associated with pain improvement. We hypothesized this relationship was mediated by patient self-efficacy since expectations of improvement may enhance one's ability to control health behaviors, and therefore health. Our aim was to examine whether self-efficacy was a mediator of the relationship observed in this trial.
Methods:
A secondary analysis of a three arm (traditional acupuncture, sham acupuncture, and wait list) trial for knee OA was conducted. Those in the acupuncture groups were equally randomized to acupuncturists trained to communicate a high or neutral expectation of treatment success (e.g. used language conveying high or unclear likelihood that acupuncture would reduce knee pain). A modified Arthritis Self-Efficacy Questionnaire and the Western Ontario McMasters (WOMAC) pain subscale were administered. Linear regression analyses were used to examine whether patient self-efficacy mediated the relationship between provider communication style and knee pain at 3 months.
Results:
High expectation provider communication was associated with patient self-efficacy, β coefficient of 0.14 (95%CI: 0.01, 0.28). Self-efficacy was associated with WOMAC pain, β coefficient of -9.29 (95%CI: -11.11, -7.47), while controlling for the provider communication style. The indirect effect a*b of -1.36 for high versus neutral expectation, (bootstrap 95% CI: -2.80, -0.15, does not include 0), supports that patient self-efficacy mediates the relationship between provider-communicated expectations of treatment effects and knee pain.
Conclusion:
Our findings suggest that clinician-conveyed expectations can enhance the benefit of treatments targeting knee OA symptoms, mediated by improved patient self-efficacy. This article is protected by copyright. All rights reserved.
Background and objective:
Communication between patients and health care practitioners is expected to benefit health outcomes. The objective of this review was to assess the effects of experimentally varied communication on clinical patients' pain.
Databases and data treatment:
We searched in July 2012, 11 databases supplemented with forward and backward searches for (quasi-) randomized controlled trials in which face-to-face communication was manipulated. We updated in June 2015 using the four most relevant databases (CINAHL, Cochrane Central, Psychinfo, PubMed).
Results:
Fifty-one studies covering 5079 patients were included. The interventions were separated into three categories: cognitive care, emotional care, procedural preparation. In all but five studies the outcome concerned acute pain. We found that, in general, communication has a small effect on (acute) pain. The 19 cognitive care studies showed that a positive suggestion may reduce pain, whereas a negative suggestion may increase pain, but effects are small. The 14 emotional care studies showed no evidence of a direct effect on pain, although four studies showed a tendency for emotional care lowering patients' pain. Some of the 23 procedural preparation interventions showed a weak to moderate effect on lowering pain.
Conclusions:
Different types of communication have a significant but small effect on (acute) pain. Positive suggestions and informational preparation seem to lower patients' pain. Communication interventions show a large variety in quality, complexity and methodological rigour; they often used multiple components and it remains unclear what the effective elements of communication are. Future research is warranted to identify the effective components.
Research into placebo effects has convincingly shown that inducing positive outcome expectations can reduce pain and other physical sensations. However, the comparative effects of different expectation inductions, such as verbal suggestion or mental imagery, and their generic effects on physical sensitivity, to different sensations such as pain, itch, and fatigue, are still largely unknown. In the current study, we assessed the individual and combined effects of verbal suggestion and imagery on pain, itch, and fatigue as indicators of physical sensitivity in a randomized study design. Healthy participants (n = 116) were given an inert (placebo) capsule that was said to be effective for reducing physical sensitivity in either the majority (positive verbal suggestion) or the minority (control verbal suggestion) of users. Subsequently, they imagined either their best possible health (positive imagery) or a typical day (control imagery). Sensitivity to pain, itch, and fatigue was tested using a cold pressor test, histamine iontophoresis, and a bicycle test, respectively. Heart rate and skin conductance were recorded continuously. Results showed that positive verbal suggestion and imagery successfully induced positive expectations, but they did not affect physical sensitivity, as indicated by sensitivity to pain, itch, or fatigue, or concurrent physiological responses. These results could indicate that the specificity and concreteness of expectation inductions might be important for their applicability in the treatment of physical symptoms.
Trial Registration
Nederlands Trial Register NTR3641
Abstract
This is the protocol for a review and there is no abstract. The objectives are as follows:
Overarching objective
To improve our understanding of the complex inter-relationship between pain, psychosocial effects, physical function and exercise.
Specific aims and objectives:
To systematically review the evidence on the impact of physical exercise on patients' pain, physical and psychosocial functioning including:
identifying the most effective formats for delivering exercise advice;
explaining why some exercise interventions may be more effective than others;
recommending exercise formats and content by constructing a "toolbox" which describes the most effective exercise interventions for healthcare providers and patients to use.
These will be achieved by conducting:
a synthesis of quantitative data on the benefits and harm of exercise interventions for improving pain, physical and psychosocial functioning;
a synthesis of qualitative data on participant's experiences, opinions and preferences of physical exercise;
a cross-studies synthesis of the quantitative and qualitative data to assess the extent to which existing evaluated interventions address the needs and concerns of people living with osteoarthritis
Hypermnesia is a phenomenon traditionally associated to hypnosis. To test this, an experiment was carried out with 87 subjects who were presented a visual stimulus -a plate with a picture, and then they were administered a questionnaire about what they had seen. A factor design was used with 8 independent groups, where the first factor was the wakefulness vs hypnosis condition in which the task was performed. The second factor was the existence or absence of suggestions to hypermnesia, and the third factor was the hypnotisability of subjects -for the wakefulness group, or the way of presentation of the memory task -for the hypnosis group. Results show a better recall in subjects who perceived and remembered the task within the wakefulness situation. Hypnosis does not seem to improve hypermnesia. The implication of this finding is discussed for event memory and its application to therapy and eyewitnesses in trials.
Placebo analgesia (PA) is accompanied by decreased activity in pain-related brain regions, but also by greater prefrontal cortex (PFC) activation, which has been suggested to reflect increases in top-down cognitive control and regulation of pain. Here we test whether PA is associated with altered prefrontal monitoring functions that could adjust nociceptive processing to a mismatch between expected and experienced pain. We recorded event-related potentials to response errors in a go/nogo task during placebo vs. a matched control condition. Error commission was associated with two well-described components, the error-related negativity (ERN) and the error positivity (Pe). Results show that the Pe, but not the ERN, was amplified during placebo analgesia compared to the control condition, with neural sources in the lateral and medial PFC. This Pe increase was driven by participants showing a placebo-induced change in pain tolerance, but was absent in the group of non-responders. Our results shed new light on the possible functional mechanisms underlying PA, suggesting a placebo-induced transient change in prefrontal error monitoring and control functions.
Previous studies suggested that areas of the pain matrix of the human brain are recruited by the processing of pain-related environmental cues such as pain-related pictures or descriptors of pain. However, it is still sketchy whether those activations are specific to the pain-relevance of the stimuli or simply reflect a general effect of negative valence or increased arousal. The present study investigates the neural mechanisms underlying the processing of pain-related, negative, positive, and neutral words. Pain-related words were matched to negative words regarding valence and arousal, and to positive words regarding arousal. Sixteen healthy subjects were scanned during two tasks, imagination and distraction, using functional MRI. When subjects were instructed to image a situation associated with the word presented (imagination task), we found increased activation within dorsolateral prefrontal cortex (DLPFC), inferior patietal gyri (IPG), and precuneus when processing pain-related words compared to other words. However, when attention was focused on a foreground task and words were presented in the background (distraction task), we found a decrease in activation within dorsal anterior cingulum (dACC) and a relative increase in activation within the subgenual ventral anterior cingulum (sACC) when processing pain related words compared to other words. Thus, activations to pain-related words are strongly modulated by the attention demands of the task. Most remarkably, the differences in processing pain-related words compared to non-pain-related words are specific to the pain-relevance of the words and cannot simply be explained by their valence or arousal.
The economic burden of low back pain (LBP) is very large and appears to be growing. It is not possible to impact this burden without understanding the strengths and weaknesses of the research on which these costs are calculated.
To conduct a systematic review of LBP cost of illness studies in the United States and internationally.
Systematic review of the literature.
Medline was searched to uncover studies about the direct or indirect costs of LBP published in English from 1997 to 2007. Data extracted for each eligible study included study design, population, definition of LBP, methods of estimating costs, year of data, and estimates of direct, indirect, or total costs. Results were synthesized descriptively.
The search yielded 147 studies, of which 21 were deemed relevant; 4 other studies and 2 additional abstracts were found by searching reference lists, bringing the total to 27 relevant studies. The studies reported on data from Australia, Belgium, Japan, Korea, the Netherlands, Sweden, the UK, and the United States. Nine studies estimated direct costs only, nine indirect costs only, and nine both direct and indirect costs, from a societal (n=18) or private insurer (n=9) perspective. Methodology used to derive both direct and indirect cost estimates differed markedly among the studies. Among studies providing a breakdown on direct costs, the largest proportion of direct medical costs for LBP was spent on physical therapy (17%) and inpatient services (17%), followed by pharmacy (13%) and primary care (13%). Among studies providing estimates of total costs, indirect costs resulting from lost work productivity represented a majority of overall costs associated with LBP. Three studies reported that estimates with the friction period approach were 56% lower than with the human capital approach.
Several studies have attempted to estimate the direct, indirect, or total costs associated with LBP in various countries using heterogeneous methodology. Estimates of the economic costs in different countries vary greatly depending on study methodology but by any standards must be considered a substantial burden on society. This review did not identify any studies estimating the total costs of LBP in the United States from a societal perspective. Such studies may be helpful in determining appropriate allocation of health-care resources devoted to this condition.
Opportunities to persuade and be persuaded are ubiquitous. What determines whether influence spreads and takes hold? This review provides an overview of evidence for the central role of subjective valuation in persuasion and social influence for both propagators and receivers of influence. We first review evidence that decisions to communicate information are determined by the subjective value a communicator expects to gain from sharing. Wenext review evidence that the effects of social influence and persuasion on receivers, in turn, arise from changes in the receiver's subjective valuation of objects, ideas, and behaviors. We then review evidence that self-related and social considerations are two key inputs to the value calculation in both communicators and receivers. Finally, we highlight biological coupling between communicators and receivers as a mechanism through which perceptions of value can be transmitted. Expected final online publication date for the Annual Review of Psychology Volume 69 is January 4, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
When we apply a physical or pharmacological treatment, there are many things that may explain the clinical improvement experienced by a patient. The drugs or physical agents applied are important, but we must also add other elements in the context of the patient–therapist relationship. Scientific evidence has proven that the placebo effect exists. This is a true biopsychosocial phenomenon produced by the context in which an intervention is carried out. Biases aside, placebo and nocebo responses are changes in patients’ symptoms, due to their participation at the therapeutic meeting, with its rituals, symbols and interactions. This multitude of signals inherent, in any intervention, is perceived and interpreted by patients and can create positive or negative expectations.
This study tested the experimental placebo effect in a group of chronic pain patients. Forty-eight patients suffering from chronic back pain participated in a randomized clinical trial that tested the efficacy of a sham opioid solution (NaCl) compared to an alleged neutral, completely inactive solution (NaCl). We shaped the placebo effect by two interventions: suggestion/instruction and conditioning. The patients were either told that the "solution reduces pain/improves physical capacity" or the "solution is neutral, a placebo". Half of each group was additionally conditioned (coupling solution with reduced experimental pain), yielding 4 subgroups with 12 participants each. Outcome measures were: the patients' clinical back pain ratings and acute pain ratings (both examined by numerical rating scale 0-10), and self-rated functional capacity (0-100%; time required for the exercise). Expected pain relief before and after solution intake was also assessed. The inactive solution (NaCl), when presented as an effective treatment (sham "opioid" solution), induced placebo analgesia as evident in lower ratings of the patients' clinical back pain (F (3.12, 144.21) = 25.05, p< .001), acute pain ratings (F (1.99, 87.40) = 18.12, p < .01) and time needed to complete a series of daily activities exercises (F (1,44) = 8.51, p < .01) as well as increased functional capacity (F (1, 44.00) 19.42, p < 0.001). The two manipulations (instruction and conditioning) changed pain expectations and they were maintained in both sham opioid groups. The results suggest that it may be clinically useful to explicitly integrate placebo analgesia responses into pain management.
When we apply a physical or pharmacological treatment, there are many things that may explain the clinical improvement experienced by a patient. The drugs or physical agents applied are important, but we must also add other elements in the context of the patient-therapist relationship. Scientific evidence has proven that the placebo effect exists. This is a true biopsychosocial phenomenon produced by the context in which an intervention is carried out. Biases aside, placebo and nocebo responses are changes in patients' symptoms, due to their participation at the therapeutic meeting, with its rituals, symbols and interactions. This multitude of signals inherent in any intervention, is perceived and interpreted by patients and can create positive or negative expectations.
Copyright © 2017 Elsevier España, S.L.U. All rights reserved.
Instructions, suggestions, and other types of social information can have powerful effects on pain and emotion. Prominent examples include observational learning, social influence, placebo, and hypnosis. These different phenomena and their underlying brain mechanisms have been studied in partially separate literatures, which we discuss, compare, and integrate in this review. Converging findings from these literatures suggest that 1) instructions and social information affect brain systems associated with the generation of pain and emotion, and with reinforcement learning, and that 2) these changes are mediated by alterations in prefrontal systems responsible for top-down control and the generation of affective meaning. We argue that changes in expectation and appraisal, a process of assessing personal meaning and implications for wellbeing, are two potential key mediators of the effects of instructions and social information on affective experience. Finally, we propose a tentative model of how prefrontal regions, especially dorsolateral and ventromedial prefrontal cortex may regulate affective processing based on instructions and socially transmitted expectations more broadly.
Increased pain perception due to the expectation to feel more pain is called nocebo effect. The present study aimed at investigating whether: 1) the mere expectation to feel more pain after the administration of an inert drug can affect the laser-pain rating and the laser-evoked potential (LEP) amplitude, and 2) the learning potentiates the nocebo effect. Eighteen healthy volunteers were told that an inert cream, applied on the right hand, would increase the laser pain and LEP amplitude to right hand stimulation. They were randomly assigned to either "verbal session" or "conditioning session". In the "verbal session",LEPs to both right and left hand stimulation were recorded at the same intensity before (baseline) and after cream application. In the "conditioning session", after an initial cream application the laser stimulus intensity was increased surreptitiously to make the subjects believe that the treatment really increased the pain sensation. Then, the cream was reapplied, and LEPs were recorded at the same stimulus intensity as at the baseline. It was found that the verbal suggestion to feel more pain disrupted the physiological habituation of the laser-pain rating and LEP amplitude to treated (right) hand stimulation. Unlike previously demonstrated for the placebo effect, the learning did not potentiate the nocebo effect.
This paper reviews some recent advances in our understanding of the effects of sham or dummy interventions on pain and other symptoms in osteoarthritis, and outlines two new approaches to the investigation of placebo and nocebo effects. We argue that the placebo effect provides us with a valuable way of investigating the nature of conditions like osteoarthritis (OA). For example, by examining which symptoms, biochemical markers or imaging features do or do not respond to placebo, we might learn more about the relationships between pathology and symptoms in OA. Placebo and nocebo effects are positive or negative outcomes resulting from the human interactions and contexts in which healthcare consultations take place. Subtle changes in behaviours and the environments in which consultations take place can have major effects on pain and other symptoms being experienced by people with OA. Nocebo effects are particularly powerful, leading to many health-care professionals causing unintended harm to their clients. Based on our own research, we conclude that beneficial outcomes are most likely to occur when both the health-care professional and the client feel safe and relaxed, and when the experiences of the client are validated by the health-care professional. These findings have important implications for clinical practice. We believe that research in this field needs to be 'trans-disciplinary', escaping from the constraints of the purely biomedical, deterministic, positivist paradigm of most medical research. We provide the example of our own work which combines performance studies and scholarship, with psychology and medicine.
Introduction:
Placebo and nocebo represent complex and distinct psychoneurobiological phenomena in which behavioural and neurophysiological modifications occur together with the application of a treatment. Despite a better understanding of this topic in the medical field, little is known about their role in physiotherapy.
Purpose:
The aim of this review is: a) to elucidate the neurobiology behind placebo and nocebo effects, b) to describe the role of the contextual factors as modulators of the clinical outcomes in rehabilitation and c) to provide clinical and research guidelines on their uses.
Implications:
The physiotherapist's features, the patient's features, the patient-physiotherapist relationship, the characteristics of the treatment and the overall healthcare setting are all contextual factors influencing clinical outcomes. Since every physiotherapy treatment determines a specific and a contextual effect, physiotherapists should manage the contextual factors as a boosting element of any manual therapy to improve placebo effects and avoid detrimental nocebo effects.
Background:
Placebo analgesia refers to the reduction in pain due to the administration of an inert treatment. It is induced by expectations of pain relief which are enhanced by learning mechanisms. In healthy humans, prior positive experiences enhance the placebo response. However, the effects of patients' prior experiences with treatment on placebo responses have not yet been examined. This study investigated how verbal information, learning and treatment history influence the magnitude of placebo analgesia in chronic pain.
Methods:
We administered a pharmacological placebo intervention in a sample of chronic pain patients (n = 49) who were seeking treatment in an outpatient pain clinic. Analyses were based on placebo responders.
Results:
We found that verbal information about a potent pain-relieving effect of the intervention induced a large placebo analgesic response to both acute experimental (F(1,44) = 43.35, p < 0.001) and chronic pain (F(1,44) = 37.72, p < 0.001). However, the placebo responses to experimental and chronic pain were not significantly related (r = 0.012, p = 0.95). An additional conditioning procedure did not significantly enhance placebo analgesia. Treatment history modulated the magnitude of the placebo response: patients with a more negative pain-related treatment history reported significantly larger placebo responses to their own chronic pain (τ = 0.271, p = 0.044).
Conclusions:
We could show that placebo responses to both acute and chronic pain are high in pain treatment settings and that treatment history modulates this effect. Different mechanisms might underlie placebo responses to acute and chronic pain. Our findings highlight the necessity of considering placebo responses and treatment history in the treatment of chronic pain. WHAT DOES THIS STUDY ADD?: Placebo analgesia following verbal information of potent pain relief is high in chronic pain patients in a clinical setting. It is modulated by treatment history. Different mechanisms might underlie placebo analgesia to acute and chronic pain.
Pain is an ambiguous perception: the same pain stimulation can be perceived differently in different contexts, producing different experiences, ranging from mild to unbearable pain. It can be even experienced as a rewarding sensation within the appropriate context. Overall, placebo and nocebo effects appear to be very good models to understand how the psychosocial context modulates the experience of pain. In this review, we examine the effects of different contexts on pain, with a specific focus on the neurobiological mechanisms. Positive and rewarding contexts inform the patients that an effective treatment is being delivered and are capable of producing pain relief through the activation of specific systems such as opioids, cannabinoids and dopamine. Conversely, a negative context can produce pain exacerbation and clinical worsening through the modulation of different systems, such as the activation of cholecystokinin and the deactivation of opioids and dopamine. In addition, when a therapy is delivered unbeknownst to the patient, its effects are reduced. A better understanding of the neurobiological underpinnings of the context-pain interaction is a challenge both for future pain research and for good clinical practice.
Nearly 20% of patients are dissatisfied following well-performed total knee arthroplasty with good functional outcomes. Surgeons must understand the drivers of dissatisfaction to minimize the number of unhappy patients following surgery. Several studies have shown that unfulfilled expectations are a principal source of patient dissatisfaction. Patients contemplating total knee arthroplasty expect pain relief, improved walking ability, return to sports, and improvement in psychological well-being and social interactions. However, patients are typically overly optimistic with regard to expected outcomes following surgery. Patient expectations and satisfaction can be influenced by age, socioeconomic factors, sex, and race. The interplay of these factors can be complex and specific to each person. Published data on clinical and functional outcomes show that persistence of symptoms, such as pain, stiffness, and failure to return to preoperative levels of function, are common and normal. Therefore, the surgeon needs to help the patient to establish realistic expectations.
Accumulating evidence suggests an association between patient pretreatment expectations and numerous health outcomes. However, it remains unclear if and how expectations relate to outcomes following treatments in multidisciplinary pain programs. The present study aims at investigating the predictive association between expectations and clinical outcomes in a large database of chronic pain patients. In this observational cohort study, participants were 2272 patients treated in one of three university-affiliated multidisciplinary pain treatment centers. All patients received personalized care including medical, psychological and/or physical interventions. Patient expectations regarding pain relief and improvements in quality of life and functioning were measured prior to the first visit to the pain centers and served as predictor variables. Changes in pain intensity, depressive symptoms, pain interference and tendency to catastrophize, as well as satisfaction with pain treatment and global impressions of change at 6-month follow-up were considered as treatment outcomes. Structural equation modeling analyses showed significant positive relationships between expectations and most clinical outcomes, and this association was largely mediated by patients' global impressions of change. Similar patterns of relationships between variables were also observed in various subgroups of patients based on sex, age, pain duration, and pain classification. Such results emphasize the relevance of patient expectations as a determinant of outcomes in multimodal pain treatment programs. Further, the results suggest that superior clinical outcomes are observed in individuals who expect high positive outcomes as a result of treatment.
Placebo effects are beneficial effects that are attributable to the brain-mind responses to the context in which a treatment is delivered rather than to the specific actions of the drug. They are mediated by diverse processes - including learning, expectations and social cognition - and can influence various clinical and physiological outcomes related to health. Emerging neuroscience evidence implicates multiple brain systems and neurochemical mediators, including opioids and dopamine. We present an empirical review of the brain systems that are involved in placebo effects, focusing on placebo analgesia, and a conceptual framework linking these findings to the mind-brain processes that mediate them. This framework suggests that the neuropsychological processes that mediate placebo effects may be crucial for a wide array of therapeutic approaches, including many drugs.
The present study aimed to determine how the therapist's approachabout intervention may influence TENS-induced hypoalgesia.
One hundred and sixty-one healthy subjects agreed to participate in this study and had their demographics, perceived pain intensity, pressure pain threshold (PPT), anxiety level and the state of anxiety inventory (STAI-S) score measured. Subsequently, subjects were randomly assigned into six study groups, three active and three placebo TENS associated with positive, negative or neutral approaches about electrical stimulation, as given by the investigator. After the treatment, all parameters were reassessed.
Active TENS-treated subjects receiving either positive or neutral expectations about intervention showed a significant increase in pressure pain threshold (PPT) (P<0.02) compared to pre-treatment; however, this was not observed in the active TENS group when associated with negative expectations. The intensity of perceived pain was significantly reduced (P<0.02) only in the active TENS groups in association with either positive or neutral expectations. There was no significant difference in any of the variables assessed in the groups receiving placebo TENS intervention.
In this study, specifically, the negative expectations induced previously to the proposed intervention promoted unfavorable outcomes with respect to the analgesic properties of TENS, suggesting that the approach taken by the physical therapist should be used to convey positive expectations and avoid those negatives, in order to promote a more efficacious treatment.
Pain is considered a major clinical, social, and economic problem in communities around the world. In this review, we describe the incidence, prevalence, and economic burden of pain conditions in children, adolescents, and adults based on an electronic search of the MEDLINE and EMBASE databases for articles published from January 1, 2000, through August 1, 2014, using the keywords pain, epidemiology, burden, prevalence, and incidence. The impact of pain on individuals and potential risk factors are also discussed. Differences in the methodology and conduct of epidemiological studies make it difficult to provide precise estimates of prevalence and incidence; however, the burden of pain is unquestionably large. Improved concepts and methods are needed in order to study pain from a population perspective and further the development of pain prevention and management strategies.
Pain is a sensory and emotional experience that is substantially modulated by psychological, social and contextual factors. Research now indicates that the influence of these factors is even more powerful than expected and involves the therapeutic response to analgesic drugs as well as the pain experience itself, which in some circumstances can even be a form of reward. Different experimental approaches and models, both in the laboratory and in the clinical setting, have been used to better characterize and understand the complex neurobiology of pain modulation. These approaches include placebo analgesia, nocebo hyperalgesia, hidden administration of analgesics, and the manipulation of the pain-reward relationship. Overall, these studies show that different neurochemical systems are activated in different positive and negative contexts. Moreover, pain can activate reward mechanisms when experienced within contexts that have special positive meaning. Because routine medical practice usually takes place in contexts that use different rituals, these neurobiological insights might have profound clinical implications.
Self-management education programmes are complex interventions specifically targeted at patient education and behaviour modification. They are designed to encourage people with chronic disease to take an active self-management role to supplement medical care and improve outcomes.
To assess the effectiveness of self-management education programmes for people with osteoarthritis.
The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PyscINFO, SCOPUS and the World Health Organization (WHO) International Clinical Trial Registry Platform were searched, without language restriction, on 17 January 2013. We checked references of reviews and included trials to identify additional studies.
Randomised controlled trials of self-management education programmes in people with osteoarthritis were included. Studies with participants receiving passive recipients of care and studies comparing one type of programme versus another were excluded.
In addition to standard methods we extracted components of the self-management interventions using the eight domains of the Health Education Impact Questionnaire (heiQ), and contextual and participant characteristics using PROGRESS-Plus and the Health Literacy Questionnaire (HLQ). Outcomes included self-management of osteoarthritis, participant's positive and active engagement in life, pain, global symptom score, self-reported function, quality of life and withdrawals (including dropouts and those lost to follow-up). We assessed the quality of the body of evidence for these outcomes using the GRADE approach.
We included twenty-nine studies (6,753 participants) that compared self-management education programmes to attention control (five studies), usual care (17 studies), information alone (four studies) or another intervention (seven studies). Although heterogeneous, most interventions included elements of skill and technique acquisition (94%), health-directed activity (85%) and self-monitoring and insight (79%); social integration and support were addressed in only 12%. Most studies did not provide enough information to assess all PROGRESS-Plus items. Eight studies included predominantly Caucasian, educated female participants, and only four provided any information on participants' health literacy. All studies were at high risk of performance and detection bias for self-reported outcomes; 20 studies were at high risk of selection bias, 16 were at high risk of attrition bias, two were at high risk of reporting bias and 12 were at risk of other biases. We deemed attention control as the most appropriate and thus the main comparator.Compared with attention control, self-management programmes may not result in significant benefits at 12 months. Low-quality evidence from one study (344 people) indicates that self-management skills were similar in active and control groups: 5.8 points on a 10-point self-efficacy scale in the control group, and the mean difference (MD) between groups was 0.4 points (95% confidence interval (CI) -0.39 to 1.19). Low-quality evidence from four studies (575 people) indicates that self-management programmes may lead to a small but clinically unimportant reduction in pain: the standardised mean difference (SMD) between groups was -0.26 (95% CI -0.44 to -0.09); pain was 6 points on a 0 to 10 visual analogue scale (VAS) in the control group, treatment resulted in a mean reduction of 0.8 points (95% CI -0.14 to -0.3) on a 10-point scale, with number needed to treat for an additional beneficial outcome (NNTB) of 8 (95% CI 5 to 23). Low-quality evidence from one study (251 people) indicates that the mean global osteoarthritis score was 4.2 on a 0 to 10-point symptom scale (lower better) in the control group, and treatment reduced symptoms by a mean of 0.14 points (95% CI -0.54 to 0.26). This result does not exclude the possibility of a clinically important benefit in some people (0.5 point reduction included in 95% CI). Low-quality evidence from three studies (574 people) showed no signficant difference in function between groups (SMD -0.19, 95% CI -0.5 to 0.11); mean function was 1.29 points on a 0 to 3-point scale in the control group, and treatment resulted in a mean improvement of 0.04 points with self-management (95% CI -0.10 to 0.02). Low-quality evidence from one study (165 people) showed no between-group difference in quality of life (MD -0.01, 95% CI -0.03 to 0.01) from a control group mean of 0.57 units on 0 to 1 well-being scale. Moderate-quality evidence from five studies (937 people) shows similar withdrawal rates between self-management (13%) and control groups (12%): RR 1.11 (95% CI 0.78 to 1.57). Positive and active engagement in life was not measured.Compared with usual care, moderate-quality evidence from 11 studies (up to 1,706 participants) indicates that self-management programmes probably provide small benefits up to 21 months, in terms of self-management skills, pain, osteoarthritis symptoms and function, although these are of doubtful clinical importance, and no improvement in positive and active engagement in life or quality of life. Withdrawal rates were similar. Low to moderate quality evidence indicates no important differences in self-management , pain, symptoms, function, quality of life or withdrawal rates between self-management programmes and information alone or other interventions (exercise, physiotherapy, social support or acupuncture).
Low to moderate quality evidence indicates that self-management education programmes result in no or small benefits in people with osteoarthritis but are unlikely to cause harm.Compared with attention control, these programmes probably do not improve self-management skills, pain, osteoarthritis symptoms, function or quality of life, and have unknown effects on positive and active engagement in life. Compared with usual care, they may slightly improve self-management skills, pain, function and symptoms, although these benefits are of unlikely clinical importance.Further studies investigating the effects of self-management education programmes, as delivered in the trials in this review, are unlikely to change our conclusions substantially, as confounding from biases across studies would have likely favoured self-management. However, trials assessing other models of self-management education programme delivery may be warranted. These should adequately describe the intervention they deliver and consider the expanded PROGRESS-Plus framework and health literacy, to explore issues of health equity for recipients.
Background and methods
Pain Study Tracking Ongoing Responses for a Year (PainSTORY) is a longitudinal study generating some quantitative and limited qualitative data concerning the experiences of individual patients with non-malignant chronic pain. Research was conducted across 13 European countries and a total of 294 patients completed the full evaluation process over 12 months. Adult patients (>18 years old) scoring >4 on an 11-point numeric pain rating scale (NRS-11) for most days during an average week were eligible. Four waves of interviews (W1–W4) were conducted over 12 months and information was recorded regarding pain levels, the impact of pain, pain treatment and treatment-associated side effects.
Results
At 3 months, 95% of respondents rated their worst pain level over the past week as ≥4. Most respondents had felt this pain level for ≥1 year, with 47% of patients reporting NRS-11 scores of 8–10 for >2 years. At 12 months, 93% of respondents still rated their worst pain level over the past week as ≥4. The overall net percentage of respondents with ≥4 pain intensity did not change substantially over 12 months of follow up. However, 40% (119/294) of patients felt their current pain level increased and 41% (121/294) felt their current pain level decreased during this time, with just 18% (53/294) of respondents reporting no change (1% of respondents not stated). At 3 months, 30% of respondents reported being managed by a pain specialist within the last 3 months, decreasing to 13% 9–12 months later. Patients were typically taking a combination of prescribed and non-prescribed medications; approximately 10% at W1 and 14% at 12 months were prescribed a strong opioid. Among those whose current pain level decreased over the year, a slightly lower proportion of patients were taking prescription medication (78%) at 12 months than in either the group with no change to their current pain level (85%), or the group whose pain level increased over the 12 month period (87%). Pain negatively affected quality of life, with respondents reporting difficulties with daily activities, including sleeping, walking, family and social interaction. Approximately half of respondents taking prescription medication reported suffering from ‘constipation and associated symptoms’. In spite of no change in pain intensity, 51% of patients were happy with their pain management at W4.
Conclusions
The heavy individual and societal burden of uncontrolled chronic pain is demonstrated in this study. This silent epidemic has not attracted the focus of attention that it deserves. Despite the significant negative impact on individual quality of life, patients evolve to a position where they believe that chronic pain is inevitable and untreatable.
Implications
It is clear that there is a real need for a coordinated response by healthcare providers and planners across European countries. Minimum standards of care should be developed and implemented at national level. Healthcare professionals and students of these disciplines must be educated to recognise, assess and manage pain within a reasonable timeframe. Patients who are not responding to standard measures must have rapid and easy access to a comprehensive, inter-disciplinary pain service.
The effectiveness of placebo treatments depends on the recipient's expectations, which are at least in part shaped by previous experiences. Thus, positive past experience together with an accordant verbal instruction should enhance outcome expectations and subsequently lead to higher placebo efficacy. This should be reflected in subjective valuation reports and in activation of placebo-related brain structures. We tested this hypothesis in a functional magnetic resonance imaging study, where subjects experienced different levels of pain relief and conforming information about price levels for two placebo treatments during a manipulation phase, thereby establishing a weak and a strong placebo. As expected, both placebos led to a significant pain relief and the strong placebo induced better analgesic efficacy. Individual placebo value estimates reflected treatment efficacy, i.e. subjects were willing to pay more money for the strong placebo even though pain stimulation was completed at this time. On the neural level, placebo effects were associated with activation of the rostral anterior cingulate cortex, the anterior insula, and the ventral striatum and deactivations in the thalamus and secondary somatosensory cortex. However, only placebo-related responses in rostral anterior cingulate cortex were consistent across both the anticipation of painful stimuli and their actual administration. Most importantly, rostral anterior cingulate cortex responses were higher for the strong placebo, thus mirroring the behavioral effects. These results directly link placebo analgesia to anticipatory activity in the ventral striatum, a region involved in reward processing, and highlight the role of the rostral anterior cingulate cortex, as its activity consistently scaled with increasing analgesic efficacy.
The dominant theories of human placebo effects rely on a notion that consciously perceptible cues, such as verbal information or distinct stimuli in classical conditioning, provide signals that activate placebo effects. However, growing evidence suggest that behavior can be triggered by stimuli presented outside of conscious awareness. Here, we performed two experiments in which the responses to thermal pain stimuli were assessed. The first experiment assessed whether a conditioning paradigm, using clearly visible cues for high and low pain, could induce placebo and nocebo responses. The second experiment, in a separate group of subjects, assessed whether conditioned placebo and nocebo responses could be triggered in response to nonconscious (masked) exposures to the same cues. A total of 40 healthy volunteers (24 female, mean age 23 y) were investigated in a laboratory setting. Participants rated each pain stimulus on a numeric response scale, ranging from 0 = no pain to 100 = worst imaginable pain. Significant placebo and nocebo effects were found in both experiment 1 (using clearly visible stimuli) and experiment 2 (using nonconscious stimuli), indicating that the mechanisms responsible for placebo and nocebo effects can operate without conscious awareness of the triggering cues. This is a unique experimental verification of the influence of nonconscious conditioned stimuli on placebo/nocebo effects and the results challenge the exclusive role of awareness and conscious cognitions in placebo responses.
Musculoskeletal conditions are common in men and women of all ages across all socio-demographic strata of society. They are the most common cause of severe long-term pain and physical disability and affect hundreds of millions of people around the world. They impact on all aspects of life through pain and by limiting activities of daily living typically by affecting dexterity and mobility. They affect one in four adults across Europe [1]. Musculoskeletal conditions have an enormous economic impact on society through both direct health expenditure related to treating the sequelae of the conditions and indirectly through loss of productivity. The prevalence of many of these conditions increases markedly with age, and many are affected by lifestyle factors, such as obesity and lack of physical activity. The burden of these conditions is therefore predicted to increase, in particular in developing countries. The impact on individuals and society of the major musculoskeletal conditions is reviewed and effective prevention, treatment and rehabilitation considered. The need to recognise musculoskeletal conditions as a global public health priority is discussed.
Unlabelled:
In 2008, according to the Medical Expenditure Panel Survey (MEPS), about 100 million adults in the United States were affected by chronic pain, including joint pain or arthritis. Pain is costly to the nation because it requires medical treatment and complicates treatment for other ailments. Also, pain lowers worker productivity. Using the 2008 MEPS, we estimated 1) the portion of total U.S. health care costs attributable to pain; and 2) the annual costs of pain associated with lower worker productivity. We found that the total costs ranged from $560 to $635 billion in 2010 dollars. The additional health care costs due to pain ranged from $261 to $300 billion. This represents an increase in annual per person health care costs ranging from $261 to $300 compared to a base of about $4,250 for persons without pain. The value of lost productivity due to pain ranged from $299 to $335 billion. We found that the annual cost of pain was greater than the annual costs of heart disease ($309 billion), cancer ($243 billion), and diabetes ($188 billion). Our estimates are conservative because they do not include costs associated with pain for nursing home residents, children, military personnel, and persons who are incarcerated.
Perspective:
This study estimates that the national cost of pain ranges from $560 to $635 billion, larger than the cost of the nation's priority health conditions. Because of its economic toll on society, the nation should invest in research, education, and training to advocate the successful treatment, management, and prevention of pain.
Negative expectations deriving from the clinical encounter can produce negative outcomes, known as nocebo effects. Specifically, research on the nocebo effect indicates that information disclosure about potential side effects can itself contribute to producing adverse effects. Neurobiological processes play a role in the nocebo effect, and this article provides a selective review of mechanistic research on the nocebo effect. Comparatively little attention has been directed to clinical studies and their implications for daily clinical practice. The nocebo response is influenced by the content and the way information is presented to patients in clinical trials in both the placebo and active treatment conditions. Nocebo effects adversely influence quality of life and therapy adherence, emphasizing the need for minimizing these responses to the extent possible. Evidence further indicates that the informed consent process in clinical trials may induce nocebo effects. This article concludes with ethical directions for future patient-oriented research and routine practice.
Chronic pain is a pervasive problem that affects the patient, their significant others, and society in many ways. The past decade has seen advances in our understanding of the mechanisms underlying pain and in the availability of technically advanced diagnostic procedures; however, the most notable therapeutic changes have not been the development of novel evidenced-based methods, but rather changing trends in applications and practices within the available clinical armamentarium. We provide a general overview of empirical evidence for the most commonly used interventions in the management of chronic non-cancer pain, including pharmacological, interventional, physical, psychological, rehabilitative, and alternative modalities. Overall, currently available treatments provide modest improvements in pain and minimum improvements in physical and emotional functioning. The quality of evidence is mediocre and has not improved substantially during the past decade. There is a crucial need for assessment of combination treatments, identification of indicators of treatment response, and assessment of the benefit of matching of treatments to patient characteristics.
Behavioral studies have suggested that placebo analgesia is partly mediated by the endogenous opioid system. Expanding on these results we have shown that the opioid-receptor-rich rostral anterior cingulate cortex (rACC) is activated in both placebo and opioid analgesia. However, there are also differences between the two treatments. While opioids have direct pharmacological effects, acting on the descending pain inhibitory system, placebo analgesia depends on neocortical top-down mechanisms. An important difference may be that expectations are met to a lesser extent in placebo treatment as compared with a specific treatment, yielding a larger error signal. As these processes previously have been shown to influence other types of perceptual experiences, we hypothesized that they also may drive placebo analgesia. Imaging studies suggest that lateral orbitofrontal cortex (lObfc) and ventrolateral prefrontal cortex (vlPFC) are involved in processing expectation and error signals. We re-analyzed two independent functional imaging experiments related to placebo analgesia and emotional placebo to probe for a differential processing in these regions during placebo treatment vs. opioid treatment and to test if this activity is associated with the placebo response. In the first dataset lObfc and vlPFC showed an enhanced activation in placebo analgesia vs. opioid analgesia. Furthermore, the rACC activity co-varied with the prefrontal regions in the placebo condition specifically. A similar correlation between rACC and vlPFC was reproduced in another dataset involving emotional placebo and correlated with the degree of the placebo effect. Our results thus support that placebo is different from specific treatment with a prefrontal top-down influence on rACC.
For many years, placebos have been defined by their inert content and their use as controls in clinical trials and treatments in clinical practice. Recent research shows that placebo effects are genuine psychobiological events attributable to the overall therapeutic context, and that these effects can be robust in both laboratory and clinical settings. There is also evidence that placebo effects can exist in clinical practice, even if no placebo is given. Further promotion and integration of laboratory and clinical research will allow advances in the ethical use of placebo mechanisms that are inherent in routine clinical care, and encourage the use of treatments that stimulate placebo effects.
Throughout history, doctor-patient relationships have been acknowledged as having an important therapeutic effect, irrespective of any prescribed drug or treatment. We did a systematic review to determine whether there was any empirical evidence to support this theory.
A comprehensive search strategy was developed to include 11 medical, psychological, and sociological electronic databases. The quality of eligible trials was objectively assessed by two reviewers, and the type of non-treatment care given in each trial was categorised as cognitive or emotional. Cognitive care aims to influence patients' expectations about the illness or the treatment, whereas emotional care refers to the style of the consultation (eg, warm, empathic), and aims to reduce negative feelings such as anxiety and fear.
We identified 25 eligible randomised controlled trials. 19 examined the effects of influencing patients' expectations about treatment, half of which found significant effects. None of the studies examined the effects of emotional care alone, but four trials assessed a combination of both cognitive and emotional care. Three of these studies showed that enhancing patients' expectations through positive information about the treatment or the illness, while providing support or reassurance, significantly influenced health outcomes.
There is much inconsistency regarding emotional and cognitive care, although one relatively consistent finding is that physicians who adopt a warm, friendly, and reassuring manner are more effective than those who keep consultations formal and do not offer reassurance.
The high price of pain: the economic impact of persistent pain in Australia
- Mbf Foundation
MBF Foundation. The high price of pain: the economic impact of persistent pain in Australia.
Access Economics Pty Limited (MBF Foundation);
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