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Errors put organisms in danger. Upon error commission, error processing allows for the updating of behavior that proved ineffective in light of the current context and goals, and for the activation of behavioral defensive systems. Pain, on the other hand, signals actual or potential danger to one's physical integrity and, likewise, motivates protective behavior. These parallels suggest the existence of cross-links between pain and error processing but so far their relationship remains elusive. In this review, we tie together findings from the field of pain research with those from electroencephalography studies on error processing [specifically the Error Related Negativity (ERN) and Positivity (Pe)]. More precisely, we discuss three plausible associations: Firstly, pain may enhance error processing as it increases error salience. Secondly, persons fearful of pain may be particularly vigilant towards painful errors and thus show a stronger neural response to them. Thirdly, the ERN as a component of the neural response to error commission is considered an endophenotype of threat sensitivity. As high sensitivity to pain threats is known to incite avoidance behavior, this raises the intriguing possibility that neural signatures of error processing predict pain-related protective behaviors, such as avoidance. We propose an integration of these findings into a common framework to inspire future research. Perspectives Inspired by research in anxiety disorders, we discuss the potential bi-directional relationships between error processing and pain, and identify future directions to examine the neural and psychological processes involved in acute and chronic pain and respective avoidance behavior.

The effects of expectations on pain perception are often studied using large differences in pain probabilities between experimental conditions, although they may be far more subtle in clinical contexts and, therefore, more difficult to detect. The current study aimed to investigate at which point subtle differences in pain probabilities can be detected and lead to differentiable expectations and perceptions. Furthermore, we investigated whether instructions can aid learning from experience and enhance subsequent pain modulatory effects. During a predictive learning task, participants were presented with 5 different cues, followed by either a high and low noxious stimulus. They learned about the different cue-stimulus contingencies either solely through experience (LEARN, N = 40) or a combination of experience and explicit information about the cue-stimulus contingencies (INSTRUCT, N = 40). We found that without explicit information, picking up the different pain probabilities was challenging, while explicit instruction significantly improved their detection. As revealed by drift diffusion modeling, learning from experience was insufficient for the development of a bias towards low pain even when it was highly likely. By contrast, when explicit information was provided, perception became more nuanced with the direction and extent of bias, capturing the subtle differences in pain probabilities. These findings highlight that the use of instructions to foster the detection of subtle pain improvements during pain treatment to enhance their cognitive pain modulatory effects warrant further investigation. ispartof: Pain vol:163 issue:1 pages:137-145 ispartof: location:United States status: published

Pain can be considered as a signal of “bodily error”: Errors – discrepancies between the actual and optimal/targeted state – can put organisms at danger and activate behavioral defensive systems. If the error relates to the body, pain is the warning signal that motivates protective action such as avoidance behavior to safeguard our body’s integrity. Hence, pain shares the functionality of errors. On the neural level, an important error processing component is the error-related negativity (ERN), a negative deflection in the electroencephalographic (EEG) signal generated primarily in the anterior cingulate cortex within 100 ms after error commission. Despite compelling evidence that the ERN plays an important role in the development of various psychopathologies and is implicated in learning and adjustment of behavior, its relation to pain-related avoidance has not yet been examined. Based on findings from anxiety research, it seems conceivable that individuals with elevated ERN amplitudes are more prone to engage in pain-related avoidance behavior, which may, under certain conditions, be a risk factor for developing chronic pain. Consequently, this new line of research promises to contribute to our understanding of human pain. As in most novel research areas, a first crucial step for integrating the scientific fields of ERN and pain is developing a paradigm suited to address the needs from both fields. The present manuscript presents the development and piloting of an experimental task measuring both ERN and avoidance behavior in response to painful mistakes, as well as the challenges encountered herein. A total of 12 participants underwent one of six different task versions. We describe in detail each of these versions, including their results, shortcomings, our solutions, and subsequent steps. Finally, we provide some advice for researchers aiming at developing novel paradigms.Keywords: error-related negativity, avoidance behavior, chronic pain, experimental psychopathology, experimental paradigm

OBJECTIVES: Worry is the most common psychological complaint among patients with Inflammatory Bowel Disease (IBD). This study aimed to translate and test the psychometric properties the Rating Form of IBD Patient Concerns (RFIPC) among Dutch-speaking patients with IBD in Belgium. It also aimed to describe worries and concerns, and to examine possible differences in worry patterns between patients with different disease types and disease activities. METHODS: The RFIPC was translated into Dutch following the guidelines of the Rome Foundation and was completed by patients with Crohn's disease (CD, n = 336) and ulcerative colitis (UC, n = 160). To test concurrent validity, the Depression Anxiety Stress Scales (DASS-21) were used. Factor structure was examined with confirmatory factor analysis. RESULTS: The four-factor structure including subscales 'impact of the disease', 'sexual intimacy', 'complications of the disease' and 'body stigma' was confirmed in the Dutch sample. All factors had high internal consistency (>.70). Correlations with DASS-21 suggest good concurrent validity, all rs>.30, ps

The fear-avoidance model of chronic pain predicts that catastrophic (mis)interpretation of pain elicits pain-related fear that in turn may spur avoidance behaviour leading to chronic pain disability. Here we investigated whether performing a movement to avoid a painful stimulus in the context of a novel movement increases threat and pain-related fear towards this novel movement, and whether avoidance behaviour persisted when given the choice between performing the acquired movement to avoid a painful stimulus or an alternative, novel movement. Applying a robotic arm-reaching task, participants could choose between two movements to reach a target location: a short, but painful movement trajectory, or a longer non-painful movement trajectory. After avoidance acquisition, the option to choose the painful trajectory was removed. The Experimental Group (N=50) could choose between the longest trajectory or a novel intermediate trajectory, whereas the Control Group (N=50) was allowed to only perform the novel trajectory. In a final test, participants of both groups were allowed to choose any of the three trajectories. Post-acquisition, Experimental Group participants showed elevated pain-expectancy and pain-related fear towards the novel trajectory, compared to the Control Group. During test, the Experimental Group participants persisted in performing the longest pain-free (avoidance) trajectory, and were less likely to choose the novel trajectory. In addition, these participants maintained higher levels of pain-related fear for the novel trajectory compared to the Control Group. These findings suggest that avoidance in the context of other neutral activities/movements may lead to the development and maintenance of threat appraisals and irrational fears. ispartof: Pain vol:162 issue:3 pages:875-885 ispartof: location:United States status: published

Experimental data suggest that associative learning can influence defensive avoidance behavior and pain perception in humans. However, whether voluntary movements can become conditioned stimuli and influence pain responses has yet to be evaluated. Forty healthy volunteers participated in this study. Electrocutaneous stimuli applied to the shoulder at pain threshold level (UStest) and at pain tolerance level (US) were determined prior to a movement-conditioning paradigm. First, reaching movements to visual cues shown on one side of a computer screen were associated with the US (CS+ movements) on 80% of trials, whereas reaching movements to visual stimuli shown on the other side were never associated with the nociceptive-US (CS- movements). Next, participants underwent a test phase in which movements to visual cues on both sides were paired with the UStest on 50% of trials. During the test phase, participants were asked to evaluate if the movement was painful (yes/no) and to rate pain intensity after each trial. Movement onset and duration as well as skin conductance responses (SCR) were collected. The UStest stimuli were more likely to be perceived as painful and were also rated as more painful during CS+ movements. Movement onset latency and SCRs were significantly higher in anticipation of the CS+ movement as compared to the CS- movement. These findings suggest that pain can be conditioned to voluntary movements. ispartof: Pain vol:161 issue:10 pages:2321-2329 ispartof: location:United States status: published

OBJECTIVES: This systematic review examined studies that used mediation analysis to investigate the mechanisms of action of cognitive-behavioral, mind-body, and exercise-based interventions for pain and disability in people with chronic primary musculoskeletal pain. MATERIALS AND METHODS: We searched 5 electronic databases for articles that conducted mediation analyses of randomized controlled trials to either test or estimate indirect effects. RESULTS: We found 17 studies (n=4423), including 90 mediation models examining the role of 22 putative mediators on pain or disability, of which 4 had partially mediated treatment effect; 8 had mixed results, and 10 did not mediate treatment effect. The conditions studied were chronic whiplash-associated pain, chronic low back pain, chronic knee pain, and mixed group of chronic primary musculoskeletal pain. DISCUSSION: We observed that several of the studies included in our systematic review identified similar mechanisms of action, even between different interventions and conditions. However, methodological limitations were common. In conclusion, there are still substantial gaps with respect to understanding how cognitive-behavioral, mind-body, and exercise-based interventions work to reduce pain and disability in people with chronic primary musculoskeletal pain.

Background and Aims Disease-related behaviours that may maintain or worsen symptom burden remain largely unexplored in inflammatory bowel disease [IBD]. In this study, we developed and validated an instrument assessing IBD-related, modifiable behaviours and explored which behaviours prospectively correlate with fatigue, a debilitating and common symptom in IBD. Methods Initially, 72 items reflecting IBD-related behaviours were generated based on literature review and input from clinicians and people diagnosed with IBD. During wave 1, 495 IBD patients rated to what extent each behaviour was applicable to them. Additionally, disease activity, fatigue, IBD-related concerns and psychological variables were assessed. During a follow-up visit 4–12 weeks later [wave 2], a random selection of 92 patients from wave 1 completed the measures assessing the IBD-related behaviours, disease activity and fatigue once more. Results A principal component analysis with oblique rotation revealed seven components in the 72 IBD behaviours, which could be interpreted as: [1] Avoiding food and activities, [2] Access to toilets, [3] Avoidance of sex, [4] Cognitive avoidance, [5] Not sharing with others, [6] Alternative treatments and [7] Disease management. Each component was reduced to three to five representative items, resulting in a final, 25-item IBD-Bx questionnaire showing good concurrent validity [alphas > 0.63] and reliability. Almost all components were cross-sectionally related to levels of fatigue. Avoiding food and activities and Access to toilets significantly predicted fatigue at wave 2 when controlling for baseline fatigue. Conclusions The IBD-Bx is a valid and reliable questionnaire of IBD-related behaviours, some of which predict future fatigue burden.

BACKGROUND: Studies using somatic pain models have shown the hypoalgesic effects of slow, deep breathing. We evaluated the effect of slow, deep breathing on visceral pain and explored putative mediating mechanisms including autonomic and emotional responses.METHODS: Fifty-seven healthy volunteers (36 females, mean age = 22.0 years) performed controlled, deep breathing at a slow frequency (6 breaths per minute), controlled breathing at a normal frequency (14 breaths per minute; active control), and uncontrolled breathing (no-treatment control) in randomized order. Moderate painful stimuli were given during each condition by delivering electrical stimulation in the distal esophagus. Participants rated pain intensity after each stimulation. Heart rate variability and self-reported arousal were measured during each condition.KEY RESULTS: Compared to uncontrolled breathing, pain intensity was lower during slow, deep breathing (Cohen's d = 0.40) and normal controlled breathing (d = 0.47), but not different between slow, deep breathing and normal controlled breathing. Arousal was lower (d = 0.53, 0.55) and heart rate variability was higher (d = 0.70, 0.86) during slow, deep breathing compared to the two control conditions. The effect of slow, deep breathing on pain was not mediated by alterations in heart rate variability or arousal but was moderated by pain catastrophizing.CONCLUSIONS AND INFERENCES: Slow, deep breathing can reduce visceral pain intensity. However, the effect is not specific to the slow breathing frequency and is not mediated by autonomic or emotional responses, suggesting other underlying mechanisms (notably distraction). Whether a long-term practice of slow, deep breathing can influence (clinical) visceral pain warrants to be investigated.

Background A substantial group of patients with inflammatory bowel disease (IBD) experience fatigue, even while in clinical remission. At present, disease-specific behaviours that maintain or worsen symptom burden including fatigue have not been explored. We developed a questionnaire evaluating IBD-specific avoidance behaviour and investigated how this relates to self-reported fatigue. Methods This study was a close collaboration between the psychology and gastroenterology department of our tertiary referral centre. A 72-item IBD-specific avoidance behaviour questionnaire (IBD-B) was generated based on literature review and input from clinicians and a patient focus group (n = 10). Between July 2018 and March 2019, 500 consecutive IBD patients were included at our infusion unit (wave 1) (participation rate 79%, 48% male, 66% Crohn’s disease (CD), median age 40). Patients completed the 72-item IBD-B, a demographic questionnaire, patient-reported outcome assessing disease activity (PRO2) and a Visual Analogue Scale (VAS) for fatigue. Test–retest reliability was assessed in 89 patients (54% male, 70% CD, median age of 40) who completed the IBD-B, PRO2 and VAS fatigue scale a second time after 4–12 weeks (wave 2). Clinical remission was defined as an abdominal pain score ≤1 and a liquid to very soft stool frequency ≤1.5 in CD patients and as no rectal bleeding and a stool frequency ≤1 in patients with ulcerative colitis (UC). A principal component analysis (PCA) was then used to reduce the number of items and investigate the underlying factor structure of the IBD-B. The predictive value of IBD-specific behaviours for fatigue was finally investigated both cross-sectionally and prospectively. Results At wave 1, 46% and 69% of CD and UC patients, respectively, were in clinical remission. PCA suggested a reduction of the 72-item to a final 25-item IBD-B and a seven-factor solution for use in clinical practice (loading factors >0.5, Table 1). The final 25-item IBD-B showed good psychometric properties. The median (IQR) total IBD-B and fatigue scores were, respectively, 29 (40-20) and 52 (77-25) for patients in clinical remission compared with 38 (48-28) and 74 (87-50) for patients not in clinical remission (both p < 0.01). Both cross-sectional and prospective significant correlations between IBD-B factors and fatigue were demonstrated (Table 2). Conclusion The IBD-B is a valuable tool to accurately measure IBD-specific avoidance behaviour in IBD patients. IBD patients without clinical remission report higher IBD-B values and show a higher correlation between avoidance behaviour and fatigue. Further research should now focus on identifying predictors for fatigue in IBD patients in clinical remission.

Pain can be considered as a signal of "bodily error": errors put organisms at danger and activate behavioral defensive systems. If the error is of physical nature, pain is the warning signal that motivates protective action such as avoidance behavior to safeguard our body's integrity. Interestingly, an important component of neural error processing, the error-related negativity (ERN), has been found to be related to avoidance in anxiety disorders. The present study is the first to extend these findings to pain and investigate the relationship between ERN and pain-related avoidance behavior. It was hypothesized that individuals with larger ERN amplitudes would show more pain-related avoidance behavior and would be more persistent in their avoidance despite changes in the environment. Fifty-three healthy individuals performed the Eriksen flanker task during which their brain activity on correct and erroneous motor responses was recorded by means of high-density electroencephalography. Avoidance behavior was assessed with an arm reaching task using the HapticMaster robot arm. The results showed that, in contrast to our hypothesis, avoidance was not related to ERN amplitudes. Surprisingly, persons with elevated ERN amplitudes showed low levels of avoidance specifically during early acquisition trials. In contrast to earlier findings in anxiety disorders, individuals with elevated ERN amplitudes did not engage in more pain-related avoidance behavior. In fact, the opposite pattern was found at the start of acquisition: individuals with higher compared with lower ERN amplitudes were slower in learning to avoid pain. Replications and future studies on the relationship between ERN and avoidance behavior are needed. ispartof: Pain vol:163 issue:2 pages:E190-E201 ispartof: location:United States status: Published online

Tinnitus is the perception of a phantom sound and the patient's reaction to it. Although much progress has been made, tinnitus remains a scientific and clinical enigma of high prevalence and high economic burden, with an estimated prevalence of 10%-20% among the adult population. The EU is funding a new collaborative project entitled "Unification of Treatments and Interventions for Tinnitus Patients" (UNITI, grant no. 848261) under its Horizon 2020 framework. The main goal of the UNITI project is to set the ground for a predictive computational model based on existing and longitudinal data attempting to address the question of which treatment or combination of treatments is optimal for a specific patient group based on certain parameters. Clinical, epidemiological, genetic and audiological data, including signals reflecting ear-brain communication, as well as patients' medical history, will be analyzed making use of existing databases. Predictive factors for different patient groups will be extracted and their prognostic relevance validated through a Randomized Clinical Trial (RCT) in which different patient groups will undergo a combination of tinnitus therapies targeting both auditory and central nervous systems. From a scientific point of view, the UNITI project can be summarized into the following research goals: (1) Analysis of existing data: Results of existing clinical studies will be analyzed to identify subgroups of patients with specific treatment responses and to identify systematic differences between the patient groups at the participating clinical centers. (2) Genetic and blood biomarker analysis: High throughput Whole Exome Sequencing (WES) will be performed in well-characterized chronic tinnitus cases, together with Proximity Extension Assays (PEA) for the identification of blood biomarkers for tinnitus. (3) RCT: A total of 500 patients will be recruited at five clinical centers across Europe comparing single treatments against combinational treatments. The four main treatments are Cognitive Behavioral Therapy (CBT), hearing aids, sound stimulation, and structured counseling. The consortium will also make use of e/m-health applications for the treatment and assessment of tinnitus. (4) Decision Support System: An innovative Decision Support System will be implemented, integrating all available parameters (epidemiological, clinical, audiometry, genetics, socioeconomic and medical history) to suggest specific examinations and the optimal intervention strategy based on the collected data. (5) Financial estimation analysis: A cost-effectiveness analysis for the respective interventions will be calculated to investigate the economic effects of the interventions based on quality-adjusted life years. In this paper, we will present the UNITI project, the scientific questions that it aims to address, the research consortium, and the organizational structure.

ispartof: Pain vol:163 issue:4 pages:604-609 ispartof: location:United States status: published

Compared to the field of anxiety research, the use of fear conditioning paradigms for studying chronic pain is relatively novel. Developments in identifying the neural correlates of pain-related fear are important for understanding the mechanisms underlying chronic pain and warrant synthesis to establish the state-of-the-art. Using effect-size signed differential mapping, this meta-analysis combined nine MRI studies and compared the overlap in these correlates of pain-related fear to those of other non-pain-related conditioned fears (55 studies). Pain-related fear was characterized by neural activation of the supramarginal gyrus, middle temporal gyrus, inferior/middle frontal gyri, frontal operculum and insula, pre-/post-central gyri, medial frontal and (para-)cingulate cortex, hippocampus, thalamus, and putamen. There were differences with other non-pain-related conditioned fears, specifically in the inferior frontal gyrus, medial superior frontal gyrus, post-central gyrus, middle temporal gyrus, parieto-occipital sulcus, and striatum. We conclude that pain-related and non-pain-related conditioned fears recruit overlapping but distinguishable networks, with potential implications for understanding the mechanisms underlying different psychopathologies. ispartof: Neuroscience And Biobehavioral Reviews vol:119 pages:52-65 ispartof: location:United States status: published

BackgroundMaladaptive defensive responses such as excessive avoidance behavior have received increasing attention as a main mechanism for the development and maintenance of chronic pain complaints. However, another defensive response which is commonly studied in animals as a proxy for fear is freezing behavior. No research to date has investigated human freezing behavior in the context of pain. In addition, there is an increasing realization that social context can affect pain-relevant processes such as pain experience and pain behavior but less is known about the effects of social context on defensive responses to pain. Hence, this study investigated freezing behavior and facial pain expression in the context of pain, and their modulation by social context.MethodsHealthy, pain-free participants (N = 39) stood on a stabilometric force platform in a threatening or safe social context, which was manipulated using angry or happy facial stimuli. In some trials, an auditory cue (conditioned stimulus; CS) predicted the occurrence of painful electrocutaneous stimulus (unconditioned stimulus; pain-US). We assessed body sway (an index of freezing), heart rate, facial pain expression, self-reported pain intensity, unpleasantness, and pain-US expectancy during the CS and the context alone (no CS).ResultsThe results were mixed. Neither the anticipation of pain, nor social context affected body sway. Heart rate and painful facial expression were reduced in the threatening social context at high anxiety levels. A threatening social context also elicited higher pain-US expectancy ratings. In sum, a threatening social context increases the expectation of pain, but reduces the facial expression of pain and lowers heart rate in highly anxious individuals.

Deep breathing exercises are commonly used for several health conditions including pain and hypertension. Various techniques are available to practice deep breathing, whereas possible differential psychophysiological effects have not been investigated. We compared four deep breathing techniques and examined outcomes in blood pressure variability, respiratory sinus arrhythmia, baroreflex function, and emotional state. Healthy adult volunteers performed pursed-lips breathing, left and right unilateral nostril breathing, and deep breathing with an inspiratory threshold load (loaded breathing), all at a frequency of 0.1 Hz (i.e., controlled breathing) and for three minutes each. Results showed that blood pressure variability was higher during loaded breathing versus other conditions and higher during pursed-lips breathing versus left and right unilateral nostril breathing. Respiratory sinus arrhythmia was higher during loaded breathing versus other conditions and higher during pursed-lips breathing versus left unilateral nostril breathing. The effect of breathing condition on respiratory sinus arrhythmia was mediated by alterations in blood pressure variability. There was no difference between the breathing conditions in baroreflex sensitivity or effectiveness. Participants rated pursed-lips breathing as more calming and pleasant and with more sense of control (vs. other conditions). Overall, among the four tested deep breathing techniques, loaded breathing was associated with enhanced cardiovascular effects and pursed-lips breathing with better emotional responses, while also enhancing cardiovascular effects (albeit less than loaded breathing). These findings can be informative in applying deep breathing techniques as self-management interventions for health conditions, in which baroreceptors stimulation and autonomic and emotional modulations can be beneficial, such as pain and hypertension.

The International Classification of Diseases-11 (ICD-11) chronic pain classification includes about 100 chronic pain diagnoses on different diagnostic levels. Each of these diagnoses requires specific operationalized diagnostic criteria to be present. The classification comprises more than 200 diagnostic criteria. The aim of the Classification Algorithm for Chronic Pain in ICD-11 (CAL-CP) is to facilitate the use of the classification by guiding users through these diagnostic criteria. The diagnostic criteria were ordered hierarchically and visualized in accordance with the standards defined by the Society for Medical Decision Making Committee on Standardization of Clinical Algorithms. The resulting linear decision tree underwent several rounds of iterative checks and feedback by its developers, as well as other pain experts. A preliminary pilot evaluation was conducted in the context of an ecological implementation field study of the classification itself. The resulting algorithm consists of a linear decision tree, an introduction form, and an appendix. The initial decision trunk can be used as a standalone algorithm in primary care. Each diagnostic criterion is represented in a decision box. The user needs to decide for each criterion whether it is present or not, and then follow the respective yes or no arrows to arrive at the corresponding ICD-11 diagnosis. The results of the pilot evaluation showed good clinical utility of the algorithm. The CAL-CP can contribute to reliable diagnoses by structuring a way through the classification and by increasing adherence to the criteria. Future studies need to evaluate its utility further and analyze its impact on the accuracy of the assigned diagnoses. ispartof: Pain vol:162 issue:7 pages:2087-2096 ispartof: location:United States status: published

The aim of the study reported in this paper is to investigate the effect of slow-deep breathing (SDB) on self-reported pain, heart rate variability, and baroreflex sensitivity (BRS). These effects are examined in 3 separate experiments, each using a different phasic pain modality. For each experiment, different subjects were recruited. Eighty-three healthy female participants were instructed to breathe guided by a visual cue at a slow frequency (SDB: .1 Hz), and at a frequency close to the spontaneous breathing frequency (normal paced breathing, .2 Hz). Pain was induced during instructed breathing using electrocutaneous (experiment 1, n .31), thermal (experiment 2, n . 28), or mechanical stimuli (experiment 3, n = 24). Participants were requested to rate the intensity of each painful stimulus (Numerical Rating Scale) and subjective level of pleasantness, arousal, and dominance (self-assessment manikin). During the experiment, R-R interval, blood pressure, tidal volume, and end-tidal CO2 were continuously measured. Results for self-reported pain, self-assessment manikin, and physiological measurements were consistent across the 3 experiments. Although SDB significantly increased baroreflex sensitivity and heart rate variability, self-reported pain did not differ between breathing conditions, regardless of pain modality. Other potential mechanisms or components should be considered such as behavioral modulators including relaxation and treatment expectation.Perspective: Merely slowing down the breathing frequency to .1 Hz is not sufficient to induce hypoalgesia, despite the significant physiological effects associated with SDB compared to spontaneous breathing. (C) 2020 U.S. Association for the Study of Pain. Published by Elsevier Inc. All rights reserved.

Pain-related fear is typically associated with avoidance behavior and pain-related disability in youth with chronic pain. Youth with elevated pain-related fear have attenuated treatment responses, thus targeted treatment is highly warranted. Evidence supporting graded in-vivo exposure treatment (GET) for adults with chronic pain is considerable, but just emerging for youth. The current investigation represents the first sequential replicated and randomized single-case experimental phase design with multiple measures evaluating GET for youth with chronic pain, entitled GET Living. A cohort 27 youth (81% female) with mixed chronic pain completed GET Living. For each participant, a no-treatment randomized baseline period was compared with GET Living and 3- and 6-month follow-ups. Daily changes in primary outcomes fear and avoidance and secondary outcomes pain catastrophizing, pain intensity, and pain acceptance were assessed using electronic diaries and subjected to descriptive and model-based inference analyses (MLM). Based on individual effect size calculations, a third of participants significantly improved by the end of treatment on fear, avoidance, and pain acceptance. By follow-up over 80% of participants had improved across all primary and secondary outcomes. MLM results to examine the series of replicated cases were generally consistent. Improvements during GET Living was superior to the no-treatment randomized baseline period for avoidance, pain acceptance, and pain intensity, whereas fear and pain catastrophizing did not improve. All five outcomes emerged as significantly improved at 3-and 6-month follow-up. The results of this replicated SCED support the effectiveness of graded exposure for youth with chronic pain and elevated pain-related fear avoidance. ispartof: Pain vol:161 issue:3 pages:520-531 ispartof: location:United States status: published

Exposure in vivo has been found successful in reducing pain-related fear, disability, and experienced pain in chronic pain patients. Despite the success of exposure treatment, experimental studies show that extinction learning is fragile, raising doubts whether extinction of pain-related fear generalizes to new threatening activities after treatment. This study examined whether a particular exposure treatment, in which patients are exposed to a variety of activities (Multiple Exposure condition), promotes generalization of extinction to new threatening situations, compared to an exposure treatment in which subjects are repeatedly exposed to the same set of activities (Repeated Exposure condition). Generalization tests were combined with randomized replicated single case experimental designs (N=8). Included were patients with Complex Regional Pain Syndrome type I reporting elevated levels of pain-related fear. The Multiple Exposure treatment condition consisted of at least 15 activities to which patients were exposed once. The Repeated Exposure treatment condition exposed patients to only three activities during five sessions each. Generalization was tested by exposing patients to new fearful activities post-treatment and 6-months follow-up. Patients from both conditions performed equally well at both generalization tests. Daily measures showed that the Multiple Exposure condition is preferred to reduce fear of movement/(re)injury, pain catastrophizing and pain experience. ispartof: Behaviour Research And Therapy vol:124 ispartof: location:England status: published

ispartof: PAIN vol:159 issue:9 pages:1690-1695 ispartof: location:United States status: published

We examined how predictable and unpredictable punishment intensity contingent on error commission modulated ERN amplitudes. We recorded the ERN in 35 healthy volunteers performing the Eriksen flanker task. Errors were punished with predictable nonpainful, painful or unpredictable electrical stimulation. Furthermore, we investigated trait anxiety. We observed that ERN amplitudes did not differ across conditions, nor were there significant effects of anxiety. In contrast, we found that predictable painful punishments led to smaller Error Positivity (Pe). The effects of predictability and intensity were present in Somatosensory Evoked Potentials elicited by the punishments. N1 amplitudes were increased for painful compared to nonpainful stimulation, and P2/P3 amplitudes for painful compared to nonpainful, and for unpredictable compared to predictable stimulation. We suggest that unpredictability and increased painfulness of punishments enhance the potential motivational significance of the errors, but do not potentiate ERN amplitudes beyond the ones elicited by errors punished with predictable nonpainful stimulation. ispartof: BIOLOGICAL PSYCHOLOGY vol:165 ispartof: location:Netherlands status: published

Slow, deep breathing is being used as a self-management intervention for various health conditions including pain and hypertension. Stimulation of the arterial baroreceptors and increased vagal modulation are among the proposed mechanisms for the therapeutic effects of slow, deep breathing. We investigated whether adding inspiratory threshold load can enhance the cardiovascular responses to controlled breathing at the frequency of 0.1 Hz, a common form of slow, deep breathing. Healthy volunteers (N = 29) performed controlled breathing at 0.1 Hz (6 breaths/minute) without load and with inspiratory threshold loads of 5 cmH2 O and 10 cmH2 O. Respiratory airflow, heart rate, and blood pressure were continuously recorded. The amplitude of the systolic blood pressure variation during respiratory cycles increased with increasing loads. Respiratory sinus arrhythmia was higher during controlled breathing at 0.1 Hz with the load of 10 cmH2 O compared to without load. Baroreflex sensitivity was not affected by loads. The effect of loads on respiratory sinus arrhythmia was mediated by increasing the amplitude of systolic blood pressure variation during respiratory cycles. These results suggest that applying small inspiratory threshold loads during controlled breathing at 0.1 Hz increases cardiac vagal modulation by this breathing exercise. This effect seems to be mediated by stronger stimulation of the arterial baroreceptors because of larger systolic blood pressure swings along the respiratory cycle. The potential benefit of long-term practice of controlled breathing at 0.1 Hz with inspiratory threshold loads on baroreflex function and cardiac vagal control needs to be investigated, particularly in pain and hypertension patients.

Biases in the way that people direct their attention towards or away from pain-related information are hypothesised to contribute to the onset and severity of pain-related disorders. This systematic review summarised 24 eye-tracking studies (N = 1424) examining effects of chronic pain, stimulus valence, individual differences in pain-related constructs such as fear of pain and pain catastrophising, and experimentally-induced pain or pain-related threat on attentional processing of visual stimuli. The majority of studies suggest that people with and without chronic pain do not differ in their eye movements on pain-related stimuli, although there is preliminary evidence that gaze biases vary across subtypes of chronic pain and may be evident only for certain stimuli. In contrast, participants with and without chronic pain exhibit a general tendency to allocate more first fixations and total fixations upon pain-related compared to neutral stimuli. Fear of pain was found to have limited effects on eye movements, whereas the tendency to catastrophise about pain, the anticipation of pain, and actual experimental pain stimulation have had stronger associations with eye movements, although results have been mixed. Methodological limitations and future research directions are discussed. ispartof: Clinical Psychology Review vol:80 pages:1-20 ispartof: location:United States status: published

Supplemental Digital Content is Available in the Text., Introduction: Research on learning in placebo and nocebo has relied predominantly on Pavlovian conditioning procedures. Operant learning procedures may more accurately model learning in real-life situations in which placebo and nocebo effects occur. Objectives: To investigate the development and persistence of placebo and nocebo effects using an operant avoidance learning task. Methods: Pain-free participants (n = 58) could learn to avoid pain by performing movements that differed in difficulty and intensity of painful stimulation. Participants performed movements in 2 contexts. In the high cost of avoidance context, pain stimulus intensity reduced with increasing movement difficulty. In the low cost of avoidance context, contingencies were reversed. Participants rated pain expectations and pain intensity. During test, movement difficulties were unchanged, but participants always received a medium-intensity pain stimulus. Placebo and nocebo effects were defined as lower/higher pain intensity ratings for trajectories that previously resulted in low/high-intensity compared with medium-intensity stimulation. Results: As expected, participants acquired differential movement-pain expectations and differential movement choices. Testing with a medium-intensity pain stimulus quickly erased differences in movement choice across contexts, but differences in pain expectations were maintained. Pain modulation across context was in line with movement-pain expectations. However, we only observed placebo effects within the low cost of avoidance context and found no evidence of nocebo effects. Conclusion: Operant learning can change pain expectations, pain modulation, and pain-related avoidance behavior. Persisting pain expectations suggest that acquired pain beliefs may be resistant to disconfirmation, despite self-initiated experience with novel pain-movement contingencies.

OBJECTIVES: The purpose of this study was to assess the factor structure, reliability, and validity of the Fear of Tinnitus Questionnaire (FTQ); a brief self-report measure of people's fears about potential cognitive, emotional, behavioral, and social consequences of living with tinnitus. DESIGN: Five hundred eighty-eight Dutch-speaking adults with tinnitus completed an online battery of questionnaires measuring tinnitus-related distress, fear, catastrophizing, and quality of life. The sample was randomly split into two to perform exploratory and Bayesian confirmatory factor analyses. A subsample of participants (n = 144) completed the battery of questionnaires a second time after a 2-week interval to calculate test-retest reliability and conduct a Bland-Altman analysis. Convergent and concurrent validity of the FTQ was assessed with the complete data set and measures of tinnitus-related distress as the outcome. RESULTS: Exploratory factor analyses indicated that single- and three-factor FTQ models were both valid solutions. Posterior predictive p values for the Bayesian confirmatory factor analyses ranged between 0.51 and 0.53 indicating that the respective models were an excellent fit for the data. The FTQ showed excellent test-retest reliability (average value intraclass correlation coefficient (ICC) = 0.92; 95% confidence interval, 0.89-0.95) and in the Bland-Altman analysis, satisfactory agreement between participants' scores after a 2-week interval. Furthermore, the FTQ demonstrated good internal reliability (α = 0.83, 95% confidence interval, 0.81-0.85) and added statistically significant amounts of variance to models predicting tinnitus-related distress and interference in daily life. CONCLUSIONS: The FTQ has good psychometric properties and can be used to assess people's fear of tinnitus in research or clinical settings. Further work to establish the reliability and validity should be conducted and include an examination of a version of the FTQ that uses Likert-type response scales which might offer improved sensitivity. ispartof: Ear and Hearing vol:40 issue:6 pages:1467-1477 ispartof: location:United States status: published

Pain intensity ratings are subject to various cognitive modulations - yet the mechanisms underlying this influence are still not understood. In a conditioning protocol, pain-related expectations were induced through pairing predefined movements with a noxious or innocuous stimulus in either a predictable or unpredictable fashion. Healthy volunteers (N = 37) categorized the stimuli as either painful or nonpainful and rated its perceived intensity. Using a Hierarchical Drift Diffusion model based on the categorization data, we found that an a priori decision-making bias evolved toward the expected sensations (P < .001). In particular, our findings suggest that differences in both the amount of decision-making bias (P = .004) and the speed of sensory processing predict pain intensity ratings (P < .001). As such, changes in pain ratings could be based in either of these processes, which may require a different approach when targeted as part of psychological pain treatment. PERSPECTIVE: Changes in reported pain levels were linked to two distinct mechanisms, suggesting that increased pain reports could be attributed to either enhanced sensory processing or biased inferences. Our results might contribute to the development of person-tailored treatments based on the identification of latent mechanisms using computational models.

A classical conditioning framework is often used for clinical reasoning about pain that persists after tissue healing. However, experimental studies demonstrating classically conditioned pain in humans are lacking. The current study tested whether non-nociceptive somatosensory stimuli can come to modulate pain threshold after being paired with painful nociceptive stimuli in healthy humans. We used a differential simultaneous conditioning paradigm in which one non-painful vibrotactile conditioned stimulus (CS+) was simultaneously paired with an unconditioned painful laser stimulus (US), while another vibrotactile stimulus (CS-) was paired with a non-painful laser stimulus. After acquisition, at-pain-threshold laser stimuli were delivered simultaneously with a CS+ or CS- vibrotactile stimulus. The primary outcome was the percentage of at-threshold laser stimuli that were reported as painful. The results were as expected: after conditioning, at-threshold laser trials paired with the CS+ were reported as painful more often, as more intense, and as more unpleasant than those paired with the CS-. This study provides new evidence that pain thresholds can be modulated via classical conditioning, even when the stimulus used to test the threshold can not be anticipated. As such, it lays a critical foundation for further investigations of classical conditioning as a possible driver of persistent pain. publisher: Elsevier articletitle: Pain by Association? Experimental Modulation of Human Pain Thresholds Using Classical Conditioning journaltitle: The Journal of Pain articlelink: http://dx.doi.org/10.1016/j.jpain.2016.06.012 content_type: article copyright: © 2016 by the American Pain Society ispartof: The Journal of Pain vol:17 issue:10 pages:1105-1115 ispartof: location:United States status: published

Chronic musculoskeletal pain in adolescence is a significant public health concern with 3-5% of adolescents suffering from significant pain-related disability. Pain-related fear and avoidance of activities has been found to have a significant influence on pain outcomes in children and adolescents and is a risk factor for less favorable response to treatment. To address this need, we developed graded exposure treatment for youth with chronic pain (GET Living). We describe the rationale, design, and implementation of a two-group randomized controlled trial (RCT) enhanced with single-case experimental design (SCED) methodology with a sample of 74 adolescents with chronic musculosketal pain and their parent caregivers. GET Living includes education, behavioral exposures, and parent intervention jointly delivered by pain psychology and physical therapy providers. The multidisciplinary pain management control group includes pain psychology delivered education and pain self-management skills training (e.g., relaxation, cognitive skills) and separate physical therapy. Assessments include brief daily diaries (baseline to discharge, 7-days at 3-month and 6-month follow-up), comprehensive in-person evaluations at baseline and discharge, and questionnaire across all time points (baseline, discharge, 3-month and 6-month follow-up). Primary outcome is pain-related fear avoidance. Secondary outcome is functional disability. We also outline all additional outcomes, exploratory outcomes, covariates, and implementation measures. The objective is to offer a mechanism-based, targeted intervention to youth with musculoskeletal pain to enhance likelihood of return to function. ispartof: Contemporary Clinical Trials Communications vol:16 ispartof: location:Netherlands status: Published online

This chapter highlights the ways that individuals learn to adapt to changes due to painful experiences. Learning is the observable change in behavior due to events in the internal and external environment, and it includes non-associative (habituation and sensitization) and associative learning (Pavlovian and operant conditioning). Once acquired, new knowledge representations remain stored in memory and may generalize to perceptually or functionally similar events. Moreover, these processes are not just a consequence of pain; they may also modulate the perception of pain. In contrast to the rapid acquisition of learned responses, their extinction is slow, fragile, and context-dependent, and it only occurs through inhibitory processes. The chapter reviews features of associative forms of learning in humans that contribute to pain, pain-related distress, and disability. It concludes with a discussion of promising future directions.

BackgroundWhen suffering from chronic pain, attempts to control or avoid pain often compete with other daily activities. Engaging in one activity excludes engaging in another, equally valued activity, which is referred to as “goal conflict.” As yet, the presence and effects of goal conflicts in patients with chronic pain remain poorly understood.MethodsThis study systematically mapped the presence and experience of goal conflicts in patients with fibromyalgia compared to healthy controls. A total of 40 patients and 37 controls completed a semi-structured interview in which they first reconstructed the previous day, identified conflicts experienced during that day, and classified each of the conflicting goals in one of nine goal categories. Additionally, they assessed how they experienced the previous day and the reported conflicts.ResultsResults showed that patients did not experience more goal conflicts than healthy controls, but that they did differ in the type of conflicts experienced. Compared to controls, patients reported more conflicts related to pain, and fewer conflicts involving work-related, social or pleasure-related goals. Moreover, patients experienced conflicts as more aversive and more difficult to resolve than control participants.DiscussionThis study provides more insight in the dynamics of goal conflict in daily life, and indicates that patients experience conflict as more aversive than controls, and that conflict between pain control (and avoidance) and other valued activities is part of the life of patients.

Slow deep breathing (SDB) is commonly employed in the management of pain, but the underlying mechanisms remain equivocal. This study sought to investigate effects of instructed breathing patterns on experimental heat pain and to explore possible mechanisms of action. In a within-subject experimental design, healthy volunteers (n = 48) performed 4 breathing patterns: 1) unpaced breathing, 2) paced breathing (PB) at the participant's spontaneous breathing frequency, 3) SDB at 6 breaths per minute with a high inspiration/expiration ratio (SDB-H), and 4) SDB at 6 breaths per minute with a low inspiration/expiration ratio (SDB-L). During presentation of each breathing pattern, participants received painful heat stimuli of 3 different temperatures and rated each stimulus on pain intensity. Respiration, heart rate, and blood pressure were recorded. Compared to unpaced breathing, participants reported less intense pain during each of the 3 instructed breathing patterns. Among the instructed breathing patterns, pain did not differ between PB and SDB-H, and SDB-L attenuated pain more than the PB and SDB-H patterns. The latter effect was paralleled by greater blood pressure variability and baroreflex effectiveness index during SDB-L. Cardiovascular changes did not mediate the observed effects of breathing patterns on pain.Perspectives: SDB is more efficacious to attenuate pain when breathing is paced at a slow rhythm with an expiration that is long relative to inspiration, but the underlying mechanisms remain to be elucidated. Crown Copyright (c) 2020 Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc.

OBJECTIVE: Our aim was to establish whether Exposure, a specialized tailored treatment for chronic low back pain, has any advantages over cognitive-behavioral therapy (CBT) among individuals with high fear-avoidance levels. Second, we planned to compare short and long versions of Exposure. Third, we aimed to investigate whether Exposure can be delivered in an outpatient psychological setting. METHOD: A total of 88 Caucasian participants (55% women) were randomized to three different psychological treatment conditions, Exposure-long, Exposure-short, and CBT. All participants were suffering from chronic pain and elevated levels of pain-related anxiety and disability. The primary outcomes were disability (assessed using two different questionnaires, QBPDS and PDI) and average pain intensity; secondary outcomes included pain-related anxiety, psychological flexibility, coping strategies, and depression. Assessments took place at pretreatment, midtreatment, posttreatment, and 6-month follow-up. RESULTS: Exposure was more effective than CBT at reducing movement-related disability assessed with the QBPDS. Exposure and CBT did not differ in reduction of pain intensity or disability assessed using the PDI. Exposure-short outperformed Exposure-long after 10 sessions, meaning that individuals improved faster when they were offered fewer sessions. Exposure could be safely delivered in the psychological setting. Concerning secondary outcomes, Exposure led to greater improvements in psychological flexibility relative to CBT. CBT was more effective than Exposure at enhancing coping strategies. In Exposure, significantly more participants dropped out. CONCLUSIONS: Although being more challenging to patients, Exposure is an effective treatment, which can be delivered in a psychological treatment setting and should be offered as a short-term treatment. (PsycINFO Database Record ispartof: JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY vol:86 issue:6 pages:533-545 ispartof: location:United States status: published

AIMS: Headache has been reported to occur during cryoballoon ablation for atrial fibrillation (AF). No study has systematically analysed this phenomenon.METHODS AND RESULTS: Twenty consecutive patients with symptomatic AF underwent cryoballoon ablation without sedation. Headache was evaluated before, during, and after the first cryoapplication in every pulmonary vein (PV) using a visual representation of a head for location of the headache, a numerical rating scale (NRS) for measuring pain intensity and the short-form McGill pain questionnaire (MPQ) for qualitative analysis of pain. The order in which the PVs were ablated was randomized. Sixteen (80%) patients perceived mainly frontal headache during cryoablation. The overall NRS scores were significantly higher during (5.1 ± 1.7), compared with before (2.7 ± 1.4), and after (3.5 ± 2.2) a cryoapplication (P < 0.05). The NRS score was significantly higher during ablation of the first PV. The intensity of the perceived headache was not related to the temperature reached 150 s after initiation of a cryoapplication (P = 0.81). Of the MPQ, three sensory adjectives and one affective adjective averaged between scores 1 and 2, representing mild-to-moderate severity of pain.CONCLUSION: The majority of patients treated by balloon cryoablation experienced headache during a cryoapplication. There was no correlation between the temperature reached during a cryoballoon freeze and the intensity of the headache. Cryoballoon ablation of the first PV was significantly more painful than the remaining PVs.

In chronic musculoskeletal pain, avoidance behavior is a prominent behavioral characteristic that can manifest itself in various ways. It is also considered a crucial component in the development and maintenance of chronic pain-related disability, supposedly fueled by pain-related fear and catastrophic beliefs. Despite the frequent occurrence of avoidance behavior and its potential impact on quality of life, relatively little research has been dedicated to the nature of avoidance in chronic pain and its assessment, leaving its underlying mechanisms poorly understood. In the current paper, we stipulate some of the existing parallels between chronic pain research and more basic fear and anxiety research inspired by modern learning theories. After a brief introduction, we discuss avoidance theories that are likely apt to be applied to chronic pain, including avoidance as a response that can affect fear responding, and the role of avoidant decision making and motivational context. Finally, we will outline how these theories may impact clinical treatment. publisher: Elsevier articletitle: Avoidance behavior in chronic pain research: A cold case revisited journaltitle: Behaviour Research and Therapy articlelink: http://dx.doi.org/10.1016/j.brat.2014.11.003 content_type: article copyright: Copyright © 2014 Elsevier Ltd. All rights reserved. ispartof: Behaviour Research and Therapy vol:64 pages:31-37 ispartof: location:England status: published

BACKGROUND: Pain interferes with cognitive functioning in several ways. Among other symptoms, pain patients often report difficulties with remembering future intentions. It remains unclear, however, whether it is the pain per se that impairs prospective remembering or other factors that often characterize people with pain (e.g. poor sleep quality). In this experiment, we investigated whether prospective memory is impaired within the context of pain, and whether this impairment is enhanced when the threat value of pain is increased.METHODS: Healthy participants engaged in an ongoing word categorization task, during which they received either experimental pain stimuli (with or without threatening instructions designed to increase the threat value of pain), or no pain stimuli (no somatic stimuli and no threatening instructions). Crucially, participants were also instructed to perform a prospective memory intention on future moments that would be signalled by specific retrieval cues.RESULTS: Threatening instructions did not differentiate the pain groups in terms of pain threat value; therefore, we only focus on the difference between pain and no pain. Pain and no-pain groups performed the prospective memory intention with similar frequency, indicating that prospective memory is not necessarily impaired when the intended action has to be performed in a painful context.CONCLUSIONS: Findings are discussed in the framework of the multiprocess theory of prospective memory, which differentiates between the spontaneous and the strategic retrieval of intentions. Methodological considerations and suggestions for future research are discussed.SIGNIFICANCE: This laboratory study combines established methods from two research fields to investigate the effects of a painful context on memory for future intentions. Painful context did not impair performance of a prospective memory intention that is assumed to be retrieved by means of spontaneous processing.

Background Tinnitus affects up to 21% of the adult population with an estimated 1% to 3% experiencing severe problems. Cognitive behavioural therapy (CBT) is a collection of psychological treatments based on the cognitive and behavioural traditions in psychology and often used to treat people suffering from tinnitus. Objectives To assess the effects and safety of CBT for tinnitus in adults. Search methods The Cochrane ENT Information Specialist searched the ENT Trials Register; CENTRAL (2019, Issue 11); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 25 November 2019. Selection criteria Randomised controlled trials (RCTs) of CBT versus no intervention, audiological care, tinnitus retraining therapy or any other active treatment in adult participants with tinnitus. Data collection and analysis We used the standard methodological procedures expected by Cochrane. Our primary outcomes were the impact of tinnitus on disease-specific quality of life and serious adverse effects. Our secondary outcomes were: depression, anxiety, general health-related quality of life, negatively biased interpretations of tinnitus and other adverse effects. We used GRADE to assess the certainty of evidence for each outcome. Main results We included 28 studies (mostly from Europe) with a total of 2733 participants. All participants had had tinnitus for at least three months and their average age ranged from 43 to 70 years. The duration of the CBT ranged from 3 to 22 weeks and it was mostly conducted in hospitals or online. There were four comparisons and we were interested in outcomes at end of treatment, and 6 and 12 months follow-up. The results below only refer to outcomes at end of treatment due to an absence of evidence at the other follow-up time points. CBT versus no intervention/wait list control Fourteen studies compared CBT with no intervention/wait list control. For the primary outcome, CBT may reduce the impact of tinnitus on quality of life at treatment end (standardised mean difference (SMD) -0.56, 95% confidence interval (CI) -0.83 to -0.30; 10 studies; 537 participants; low certainty). Re-expressed as a score on the Tinnitus Handicap Inventory (THI; range 0 to 100) this is equivalent to a score 10.91 points tower in the CBT group, with an estimated minimal clinically important difference (MCID) for this scale being 7 points. Seven studies, rated as moderate certainty, either reported or informed us via personal commu nication about serious adverse effects. CBT probably results in little or no difference in adverse effects: six studies reported none and in one study one participant in the CBT condition worsened (risk ratio (RR) 3.00, 95% CI 0.13 to 69.87). For the secondary outcomes, CBT may result in a slight reduction in depression (SMD -0.34, 95% CI-0.60 to -0.08; 8 studies; 502 participants; low certainty). However, we are uncertain whether CBT reduces anxiety, improves health-related quality of life or reduces negatively biased interpretations of tinnitus (all very low certainty). From seven studies, no other adverse effects were reported (moderate certainty). CBT versus audiological care Three studies compared CBT with audiological care. CBT probably reduces the impact of tinnitus on quality of life when compared with audiological care as measured by the THI (range 0 to 100; mean difference (MD) -5.65, 95% CI -9.79 to -1.50; 3 studies; 444 participants) (moderate certainty; MCID = 7 points). No serious adverse effects occurred in the two included studies reporting these, thus risk ratios were not calculated (moderate certainty). The evidence suggests that CBT may slightly reduce depression but may result in little or no difference in anxiety or health-related quality of life (all low certainty) when compared with audiological care. CBT may reduce negatively biased interpretations of tinnitus when compared with audiological care (low certainty). No other adverse effects were reported for either group (moderate certainty). CBT versus tinnitus retraining therapy (TRT) One study compared CBT with TRT (including bilateral sound generators as per TRT protocol). CBT may reduce the impact of tinnitus on quality of life as measured by the THI when compared with TRT (range 0 to 100) (MD -15.79, 95% CI -27.91 to -3.67; 1 study; 42 participants; low certainty). For serious adverse effects three participants deteriorated during the study: one in the CBT (n = 22) and two in the TRT group (n = 20) (RR 0.45, 95% CI 0.04 to 4.64; low certainty). We are uncertain whether CBT reduces depression and anxiety or improves heal-threlated quality of life (low certainty). CBT may reduce negatively biased interpretations of tinnitus. No data were available for other adverse effects. CBT versus other active control Sixteen studies compared CBT with another active control (e.g. relaxation, information, Internet-based discussion forums). CBT may reduce the impact of tinnitus on quality of life when compared with other active treatments (SMD -0.30, 95% CI -0.55 to -0.05; 12 studies; 966 participants; low certainty). Re-expressed as a THI score this is equivalent to 5.84 points lower in the CBT group than the other active control group (MCID = 7 points). One study reported that three participants deteriorated: one in the CBT and two in the information only group (RR 1.70, 95% CI 0.16 to 18.36; low certainty). CBT may reduce depression and anxiety (both low certainty). We are uncertain whether CBT improves health-related quality of life compared with other control. CBT probably reduces negatively biased interpretations of tinnitus compared with other treatments. No data were available for other adverse effects. Authors' conclusions CBT may be effective in reducing the negative impact that tinnitus can have on quality of life. There is, however, an absence of evidence at 6 or 12 months follow-up. There is also some evidence that adverse effects may be rare in adults with tinnitus receiving CBT, but this could be further investigated. CBT fortinnitus may have small additional benefit in reducing symptoms of depression although uncertainty remains due to concerns about the quality of the evidence. Overall, there is limited evidence for CBT for tinnitus improving anxiety, heal-threlated quality of life or negatively biased interpretations of tinnitus.

Expectations about an impeding pain stimulus strongly shape its perception, yet the degree that uncertainty might affect perception is far less understood. To explore the influence of uncertainty on pain ratings, we performed a close replication of the study of Yoshida, Seymour, Koltzenburg, and Dolan (2013), who manipulated vicarious information about upcoming heat pain and found evidence for uncertainty-induced hyperalgesia. In our study, we presented eight fictitious ratings of previous participants prior the delivery of electrocutaneous pain. The vicarious information was either biased to over- or underreport pain levels based on the participant's psychometric function. We induced uncertainty by manipulating the variation of the vicarious information. As in Yoshida et al. (2013), four computational models were formulated, such that each model represented a different way of how the pain ratings might have been generated by the physical stimulus and the vicarious information. The four competing models were tested against the data of each participant separately. Using a formal model selection criterion, the best model was selected and interpreted. Contrary to the original study, the preferred model for the majority of participants suggested that pain ratings were biased towards the average vicarious information, ignoring the degree of uncertainty. Possible reasons for these diverging results are discussed.

Background An influential idea is that attentional bias to information related to pain or pain-related negative affect underlies persistent pain problems. Such information is however often ambiguous. If ambiguous input is perceived as pain or threat related, attention to this stimulus would be enhanced compared with stimuli with no (dominant) pain-/threat-related meaning. Attentional bias to ambiguous stimuli related to somatic/health threat was expected to be more pronounced with higher levels of pain catastrophizing. Methods University students performed a spatial cueing task including four types of word cues that were combinations of word content (somatic/health threat vs. non-threat), and word ambiguity (unambiguous vs. ambiguous), each presented for 500 or 750 ms. Attentional bias to somatic/health threat is reflected in larger cue validity effects for somatic/heath threat words than for non-threat words. Results In the 500-ms condition, cue validity effects were larger for threat than for non-threat words in participants reporting low catastrophizing, but did not depend on word content in participants reporting higher catastrophizing. In the 750-ms condition, cue validity effects did not depend on pain catastrophizing or word content. Cue validity effects did not significantly differ between unambiguous words and ambiguous homographs. Conclusions Low catastrophizers demonstrated attentional bias to threat content. Participants reporting higher catastrophizing showed overall enhanced attentional orienting. There was no evidence for differences in (biased) attention to unambiguous and ambiguous words. Further research is needed to determine attentional bias for ambiguous pain-/threat-related stimuli in the context of consistent attentional bias for unambiguous pain-/threat-related stimuli.

Fear of movement-related pain significantly contributes to musculoskeletal chronic pain disability. Previous research has shown that fear of movement-related pain can be classically conditioned. That is, in a differential fear conditioning paradigm, after (repeatedly) pairing a neutral joystick movement (conditioned stimulus; CS+) with a painful stimulus (unconditioned stimulus; pain-US), that movement in itself starts to elicit self-reported fear and elevated psychophysiological arousal compared to a control joystick movement (CS-) that was never paired with pain. Further, it has been demonstrated that novel movements that are more similar to the original CS+ elicit more fear than novel movements that are more similar to the CS-, an adaptive process referred to as stimulus generalization. By default, movement/action takes place in reference to the three-dimensional space: a movement thus not only involves proprioceptive information, but it also contains spatiotopic information. Therefore, the aim of this study was to investigate to what extent spatiotopic information (i.e., endpoint location of movement) contributes to the acquisition and generalization of such fear of movement-related pain besides proprioception (i.e., movement direction). In a between-subjects design, the location group performed joystick movements from the middle position to left and right; the movement group moved the joystick from left and right to the middle. One movement (CS+) was paired with pain, another not (CS-). Feature overlap between CSs typically reduces differential learning. The endpoint of both CSs in the movement group is an overlapping feature whereas in the location group the endpoint of both CSs is distinct; therefore we hypothesized that there would be less differential fear learning in the movement group compared to the location group. We also tested generalization to movements with similar proprioceptive features but different endpoint location. Following the principle of stimulus generalization, we expected that novel movements in the same direction as the CS+ but with a different endpoint would elicit more fear than novel movement in the same direction of the CS- but with a different endpoint. Main outcome variables were self-reported fear and pain-US expectancy and eyeblink startle responses (electromyographic). Corroborating the feature overlap hypothesis, the location group showed greater differential fear acquisition. Fear generalization emerged for both groups in the verbal ratings, suggesting that fear indeed accrued to proprioceptive CS features; these effects, however, were not replicated in the startle measures. ispartof: PeerJ vol:7 ispartof: location:United States status: published

This study investigated observational learning of pain-related fear and subsequent extinction after first-hand exposure to the feared stimulus. Moreover, the specific contingencies that are learned when observing others in pain were explored. A differential fear-conditioning paradigm was used, showing video models displaying either a painful (CS+ color; aversively conditioned stimulus) or a neutral (CS− color; neutrally conditioned stimulus) facial expression in the presence of a colored warm water task (WWT; observation phase). In 1 condition (open WWT cover), the model's hand was immersed in the colored liquid, while in the other condition (closed WWT cover), no contact was displayed between the model and the liquid. During exposure, participants subsequently immersed their own hand into each WWT with equal temperatures. Results revealed successful acquisition of pain-related fear. Participants with higher levels of pain catastrophizing, intolerance of uncertainty, trait fear of pain, or dispositional empathy were more prone to develop pain-related fear. Pain-related fear extinguished quickly after direct exposure to both WWTs. Contingencies between the color of the WWT and either the painful facial expressions or the assumed properties of the colored liquid were learned in both conditions. Clinical implications and limitations of the current study are discussed, providing avenues for future research in observational learning of pain-related fear. Perspective Pain-related fear promotes the development as well as the continuation of chronic pain. A better understanding of the acquisition and extinction of this fear may help to improve pain treatment programs. Furthermore, we intended to identify individuals who are more prone to develop pain-related fear.

BACKGROUND: Long-term avoidance of painful activities has shown to be dysfunctional in chronic pain. Pain may elicit escape or avoidance responses automatically, particularly when pain-related fear is high. A conflict may arise between opposing short-term escape/avoidance goals to reduce pain and long-term approach goals to receive a reward. An inhibitory control system may resolve this conflict. It was hypothesized that reduced response inhibition would be associated with greater escape/avoidance during pain, particularly among subjects with higher pain-related fear. METHODS: Response inhibition was measured with the stop-signal task, and pain-related fear with the Fear of Pain Questionnaire. Participants completed a tone-detection task (TDT) in which they could earn money while being exposed to cold pressor pain. Escape/avoidance was operationalized as the hand immersion time during a cold pressor task (CPT) and the performance on the TDT. RESULTS: Poorer response inhibition was associated with shorter CPT immersion duration and with worse TDT performance. Pain after the CPT was associated with pain-related fear, but not with response inhibition. No supportive evidence was found for the hypothesis that the relation between inhibition and escape/avoidance would be most pronounced for those with higher pain-related fear. In contrast, the relation between response inhibition and number of hits on the TDT was most pronounced for those with lower pain-related fear. CONCLUSIONS: The findings suggest that individuals with a stronger ability to inhibit responses in a stop-signal task are better able to inhibit escape/avoidance responses elicited by pain, in the service of a conflicting approach goal.

Fresh empirical evidence supports the notion that fear of movement-related pain can be acquired through associative learning. In the context of these findings, 2 ideas are appealing, yet uninvestigated. The first is that merely the intention to perform a painful movement acts as a covert conditioned stimulus (CS) inducing defensive fear responses (ie, gaining excitatory properties following Pavlovian acquisition). The second idea is that after extinction, fear of movement-related pain can easily be reinstated after unexpected painful stimuli (ie, reinstatement). In a voluntary differential conditioning movement paradigm with movements as CSs and a painful electrocutaneous stimulus as the unconditioned stimulus (pain-US), 2 groups were included (Experimental/Control). One movement (CS+) was followed by the pain-US and another movement (CS) was not during acquisition, while the CS+ was no longer reinforced during extinction. Next, the Experimental group received 2 reinstating pain-USs, whereas the Control group did not. The CS+ but not the CS evoked fear of movement-related pain in self-reports and eye-blink startles. Intriguingly, the mere intention to perform the painful movement produced higher eye-blink startle responses than the intention to perform the nonpainful movement. We also demonstrated nondifferential reinstatement in the verbal fear ratings in the Experimental group only. Perspective: This study demonstrates that the mere intention to perform a painful movement prior to the actual painful movement itself can come to elicit conditioned fear responses. These results suggest that actual movement may not be necessary to elicit pain-related fear responses, maintaining chronic pain-related fear, avoidance, and disability. (C) 2013 by the American Pain Society

Recent evidence indicates that pain-related fear can be acquired through associative learning. In the clinic, however, spreading of fear and avoidance is observed beyond movements/activities that were associated with pain during the original pain episode. One mechanism accounting for this spreading of fear is stimulus generalization. In a voluntary movement-conditioning paradigm, healthy participants received predictable pain (ie, one movement predicts pain, another does not) in one context, and unpredictable pain in another context. The former procedure is known to induce cued pain-related fear to the painful movement, whereas the latter procedure generates contextual pain-related fear. In both experimental pain contexts, we subsequently tested fear generalization to novel movements (having either proprioceptive features in common with the original painful movement or nonpainful movement). Results indicated that in the predictable pain context, pain-related fear spreads selectively to novel movements proprioceptively related to the original painful movement, and not to those resembling the original nonpainful movement. In the unpredictable context, nondifferential fear generalization was observed, suggesting persistent contextual pain-related fear and poor safety learning. These data illustrate that spreading of pain-related fear is fostered by previously acquired movement-pain contingencies. Based on recent advances in anxiety research, we proposed an innovative approach conceptualizing predictable pain as a laboratory model for fear of movement in regional musculoskeletal pain, and unpredictable pain generating contextual pain-related fear as a prototype of widespread musculoskeletal pain. Consequently, fear generalization might play an important role in spreading of pain-related fear and avoidance behavior in regional and widespread musculoskeletal pain. (c) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.