Neuromuscular electrical stimulation to combat cognitive aging in people with spinal cord injury: protocol for a single case experimental design study.

INTRODUCTION: Individuals with spinal cord injury (SCI) can experience accelerated cognitive aging. Myokines (factors released from muscle cells during contractions), such as brain-derived neurotrophic factor (BDNF), are thought to have beneficial effects on cognition. Neuromuscular electrical stimulation (NMES) was shown to elicit a large release of myokines. However, the effects of NMES on cognitive function have not been studied. OBJECTIVE: To present the study protocol for a clinical trial evaluating the effects of NMES aimed at improving cognition and BDNF. METHODS: A replicated randomized three-phases single-case experimental design (SCED) with sequential multiple baseline time series and a single-armed prospective trial will be conducted with 15 adults with chronic SCI (> 12 months after injury) above L1 neurological level undergoing 30-min quadriceps NMES, 3 days per week for 12 weeks. MAIN STUDY ENDPOINTS: Primary endpoint is cognitive performance (assessed by a smartphone test) conducted three times per week during the baseline phase with random duration of 3 to 8 weeks, the intervention phase of 12 weeks, and the follow-up phase of 3 weeks after a no measurement rest period of 12 weeks. Secondary endpoints are changes in BDNF levels and cognitive performance measured before the baseline period, before and after intervention and after a 12 weeks follow-up. CONCLUSION: This will be the first study investigating the effects of 12 weeks NMES on both cognition and BDNF levels in individuals with SCI. The SCED results provide information on individual treatment effect courses which may direct future research. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05822297, 12/01/2023).

Better Together. Group versus individual Cognitive-Behavioral Therapy for tinnitus: A Multiple-Baseline Single-Case Experimental Design.

OBJECTIVES: Chronic tinnitus is effectively treated through cognitive-behavioral therapy (CBT). Both group and individual CBT for tinnitus are effective, but no study has directly compared the two. The current study explores group versus individual CBT for tinnitus. DESIGN: A multiple-baseline single-case experimental design was employed to observe changes within/between individual and group treatments. Six participants started a 10-week CBT protocol and were equally divided into individual or group treatment. Participants were exchanged between treatments at random time points. Diary data included 14 variables on tinnitus experience (e.g. annoyance and distraction) and wellbeing (e.g. happiness and stress). Five male participants (59- to 67-year-old) completed treatment. RESULTS: Randomization tests comparing means between individual and group treatments did not reveal significant differences. Analysis of data overlap and trend (Tau-U) revealed minor significant improvements for seven variables (50%) in group treatment as compared to individual treatment. Diminished happiness and activity levels were observed in participants who went from group to individual treatment. CONCLUSIONS: Low effect sizes and homogeneity of sample restrict the generalizability of data. Group CBT indicated potential benefits when compared to individual CBT. Social learning may be an underlying process in group delivery boosting tinnitus recovery. Findings are limited to male patients with chronic disabling tinnitus.

Low back pain.

Low back pain covers a spectrum of different types of pain (eg, nociceptive, neuropathic and nociplastic, or non-specific) that frequently overlap. The elements comprising the lumbar spine (eg, soft tissue, vertebrae, zygapophyseal and sacroiliac joints, intervertebral discs, and neurovascular structures) are prone to different stressors, and each of these, alone or in combination, can contribute to low back pain. Due to numerous factors related to low back pain, and the low specificity of imaging and diagnostic injections, diagnostic methods for this condition continue to be a subject of controversy. The biopsychosocial model posits low back pain to be a dynamic interaction between social, psychological, and biological factors that can both predispose to and result from injury, and should be considered when devising interdisciplinary treatment plans. Prevention of low back pain is recognised as a pivotal challenge in high-risk populations to help tackle high health-care costs related to therapy and rehabilitation. To a large extent, therapy depends on pain classification, and usually starts with self-care and pharmacotherapy in combination with non-pharmacological methods, such as physical therapies and psychological treatments in appropriate patients. For refractory low back pain, a wide range of non-surgical (eg, epidural steroid injections and spinal cord stimulation for neuropathic pain, and radiofrequency ablation and intra-articular steroid injections for mechanical pain) and surgical (eg, decompression for neuropathic pain, disc replacement, and fusion for mechanical causes) treatment options are available in carefully selected patients. Most treatment options address only single, solitary causes and given the complex nature of low back pain, a multimodal interdisciplinary approach is necessary. Although globally recognised as an important health and socioeconomic challenge with an expected increase in prevalence, low back pain continues to have tremendous potential for improvement in both diagnostic and therapeutic aspects. Future research on low back pain should focus on improving the accuracy and objectivity of diagnostic assessments, and devising treatment algorithms that consider unique biological, psychological, and social factors. High-quality comparative-effectiveness and randomised controlled trials with longer follow-up periods that aim to establish the efficacy and cost-effectiveness of low back pain management are warranted.

Pragmatic Uncontrolled Study of Specialized Cognitive Behavioral Therapy for Adults With Chronic Tinnitus.

OBJECTIVES: Tinnitus is the perception of sound without an external source, affecting quality of life that can cause severe distress in approximately 1 to 3% of the population of people with tinnitus. Randomized controlled trials of cognitive behavioral therapy for tinnitus have demonstrated its effectiveness in improving quality of life, but the effects of their implementation on a large scale in routine practice remains unknown. Therefore, the main purpose of this study was to examine the effects of stepped-care cognitive behavioral therapy for tinnitus delivered in a tertiary audiological center of a regional hospital. Second, we wished to examine predictors of favorable outcome. DESIGN: Four hundred three adults with chronic tinnitus were enrolled in this prospective observational study (at 3 months, N=334, 8 months, N=261; 12 months, N=214). The primary outcome was health-related quality of life as measured by the Health Utilities Index III (HUI-III) at 12 months. Secondary outcomes were self-reported levels of tinnitus-related distress, disability, affective distress and tinnitus-related negative beliefs and fear. Measures were completed pre-intervention at 3 months, 8 months, and 12 months. Multilevel modeling was used to examine effects and their predictors. RESULTS: Younger participants with lower levels of tinnitus distress were more likely to dropout while those with higher tinnitus distress at baseline and quality of life were more likely to receive step 2 of treatment. MLM analyses revealed, with one exception, no relation between any baseline variable and outcome change over time. Most participants' improvement exceeded minimally clinical important difference criteria for quality of life, tinnitus-related handicap, and tinnitus distress. CONCLUSIONS: Results from this large pragmatic study complements those from randomized controlled trials of cognitive behavioral therapy for chronic tinnitus distress and supports its implementation under "real-world" conditions.

The Daily Experience of Subjective Tinnitus: Ecological Momentary Assessment Versus End-of-Day Diary.

OBJECTIVE: Traditional methods of self-report assessments are susceptible to bias (i.e., memory, recall, and recency). Ecological momentary assessment (EMA) may curb these biases by repeated momentary assessment of the participant throughout the day. High costs and participant burden may, however, impede the use of EMA. End-of-day diary (EDD) provides an attractive alternative to EMA, though no direct comparison has been performed in the tinnitus field. DESIGN: Four thousand seven-hundred thirty-two data entries were collected from nine participants undergoing cognitive behavioral treatment for tinnitus. Eleven equivalent EMA and EDD items were collected for approximately 3 months. Tinnitus experience (i.e., anger, annoyance, avoidance, distraction, fear, invasiveness, pleasantness, and sadness) and well-being (i.e., anxiety, happiness, and stress) were correlated and means compared (t-tests). RESULTS: All variables presented adequate correlation (r > 0.68) between the EMA and EDD counterparts. Small (<3.9%) significant daily mean differences between EMA and EDD were found for six variables (tinnitus anger, invasiveness, pleasantness, sadness, as well as anxiety and stress) with worse results reported in EDD. CONCLUSION: The small significant effects found may be attributed to the large number of data points. When EMA is not possible or recommended, EDD provides a viable alternative to assess tinnitus experience daily. Further research on the underlying mechanisms of tinnitus experience and recollection is warranted.

Association of pain-related threat beliefs and disability with postural control and trunk motion in individuals with low back pain: a systematic review and meta-analysis.

PURPOSE: Low back pain (LBP) individuals with high levels of fear of pain might display changes in motor behavior, which leads to disability. This study aimed to systematically review the influence of pain-related threat beliefs or disability on trunk kinematic or postural control in LBP. METHOD: Eight electronic databases were searched from January 1990 to July 1, 2020. Meta-analysis using random-effect model was performed for 18 studies on the association between pain-related threat beliefs or disability and lumbar range of motion. Pearson r correlations were used as the effect size. RESULT: Negative correlations were observed between lumbar range of motion (ROM) and pain-related threat beliefs (r = - 0.31, p < 0.01, 95% CI: - 0.39, - 0.24) and disability (r = - 0.24, p < 0.01, 95% CI: - 0.40, - 0.21). Nonsignificant correlations were reported between pain-related threat beliefs and center of pressure parameters during static standing in 75% of the studies. In 33% of the studies, moderate negative correlations between disability and postural control were observed. CONCLUSION: Motor behaviors are influenced by several factors, and therefore, the relatively weak associations observed between reduced lumbar ROM with higher pain-related threat beliefs and perceived disability, and postural control with disability are to be expected. This could aid clinicians in the assessment and planning rehabilitation interventions. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

The Perceived Opportunity to Avoid Pain Paradoxically Increases Pain-Related Fear Through Increased Threat Appraisals.

BACKGROUND: Although pain-related avoidance is mainly intended to reduce the accompanying anticipatory fear, avoidance behavior may paradoxically increase fear when a previous avoidance response is no longer available, suggesting that there is a bidirectional relationship between pain-related fear and avoidance. PURPOSE: We hypothesized that avoidance can serve as a source of information that fuels irrational pain-related threat appraisals, which, in turn, increases pain-related fear. METHODS: Participants (N = 66) were exposed to a painful heat stimulus and randomly assigned to the avoidance or control group. They were instructed to avoid the full heat intensity by pressing a stop button in the presence of a stop cue. Only avoidance group participants received a stop cue and were allowed to press the stop button, while control group participants received the same instructions but never had the opportunity to avoid the full heat intensity. In reality and unknown to participants, the intensity and duration of the heat stimulus was independent of the avoidance response. In the subsequent test phase, the avoidance response was unavailable for both groups. We measured pain-related fear, threat appraisals/harmfulness, and pain intensity. RESULTS: In line with our expectations, pain-related fear levels were higher when the avoidance response was no longer available compared to those when the avoidance response was available. Increased threat appraisals mediated the relationship between avoidance behavior and increased pain-related fear. CONCLUSIONS: The perceived opportunity to avoid increased pain-related fear through threat appraisals, suggesting a more complicated relationship between pain-related fear, threat appraisals, and avoidance behavior than the unidirectional relationships proposed in the fear-avoidance model. Clinical implications are discussed.

Behavioral Conceptualization and Treatment of Chronic Pain.

Pain is considered a hardwired signal of bodily disturbance belonging to a basic motivational system that urges the individual to act and to restore the body's integrity, rather than just a sensory and emotional experience. Given its eminent survival value, pain is a strong motivator for learning. Response to repeated pain increases when harm risks are high (sensitization) and decreases in the absence of such risks (habituation). Discovering relations between pain and other events provides the possibility to predict (Pavlovian conditioning) and control (operant conditioning) harmful events. Avoidance is adaptive in the short term but paradoxically may have detrimental long-term effects. Pain and pain-related responses compete with other demands in the environment. Exposure-based treatments share the aim of facilitating or restoring the pursuit of individual valued life goals in the face of persistent pain, and further improvements in pain treatment may require a paradigm shift toward more personalized approaches.

The Fear of Tinnitus Questionnaire: Toward a Reliable and Valid Means of Assessing Fear in Adults with Tinnitus.

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.

EULAR recommendations for the health professional's approach to pain management in inflammatory arthritis and osteoarthritis.

Pain is the predominant symptom for people with inflammatory arthritis (IA) and osteoarthritis (OA) mandating the development of evidence-based recommendations for the health professional's approach to pain management. A multidisciplinary task force including professionals and patient representatives conducted a systematic literature review of systematic reviews to evaluate evidence regarding effects on pain of multiple treatment modalities. Overarching principles and recommendations regarding assessment and pain treatment were specified on the basis of reviewed evidence and expert opinion. From 2914 review studies initially identified, 186 met inclusion criteria. The task force emphasised the importance for the health professional to adopt a patient-centred framework within a biopsychosocial perspective, to have sufficient knowledge of IA and OA pathogenesis, and to be able to differentiate localised and generalised pain. Treatment is guided by scientific evidence and the assessment of patient needs, preferences and priorities; pain characteristics; previous and ongoing pain treatments; inflammation and joint damage; and psychological and other pain-related factors. Pain treatment options typically include education complemented by physical activity and exercise, orthotics, psychological and social interventions, sleep hygiene education, weight management, pharmacological and joint-specific treatment options, or interdisciplinary pain management. Effects on pain were most uniformly positive for physical activity and exercise interventions, and for psychological interventions. Effects on pain for educational interventions, orthotics, weight management and multidisciplinary treatment were shown for particular disease groups. Underpinned by available systematic reviews and meta-analyses, these recommendations enable health professionals to provide knowledgeable pain-management support for people with IA and OA.

The Influence of Pain-Related Expectations on Intensity Perception of Nonpainful Somatosensory Stimuli.

OBJECTIVE: The extent to which pain-related expectations, known to affect pain perception, also affect perception of nonpainful sensations remains unclear, as well as the potential role of unpredictability in this context. METHODS: In a proprioceptive fear conditioning paradigm, various arm extension movements were associated with predictable and unpredictable electrocutaneous pain or its absence. During a subsequent test phase, nonpainful electrocutaneous stimuli with a high or low intensity were presented during movement execution. We used hierarchical drift diffusion modeling to examine the influence of expecting pain on the perceptual decision-making process underlying intensity perception of nonpainful sensations. In the first experiment (n = 36), the pain stimulus was never presented during the test phase after conditioning. In the second experiment (n = 39), partial reinforcement was adopted to prevent extinction of pain expectations. RESULTS: In both experiments, movements that were associated with (un)predictable pain led to higher pain expectancy, self-reported fear, unpleasantness, and arousal as compared with movements that were never paired with pain (effect sizes η2 ranging from 0.119 to 0.557; all p values < .05). Only in the second experiment-when the threat of pain remained present-we found that the expectation of pain affected decision making. Compared with the no pain condition, an a priori decision-making bias toward the high-intensity decision threshold was found with the strongest bias during unpredictable pain (effect sizes η2 ranging from 0.469 to 0.504; all p-values < .001). CONCLUSIONS: Thus, the expectation of pain affects inferential processes not only for subsequent painful but also for nonpainful bodily stimuli, with unpredictability moderating these effects, and only when the threat of pain remains present due to partial reinforcement.

EXPOSURE IN VIVO VERSUS PAIN-CONTINGENT PHYSICAL THERAPY IN COMPLEX REGIONAL PAIN SYNDROME TYPE I: A COST-EFFECTIVENESS ANALYSIS.

OBJECTIVES: The aim of this study was to evaluate the cost-effectiveness of exposure in vivo (EXP, a cognitive-behavioral treatment targeting pain-related fear) in Complex Regional Pain Syndrome Type I (CRPS-I), as compared to pain-contingent physical therapy (PPT). METHODS: Data from a randomized controlled trial were used to compare the cost-effectiveness of EXP versus PPT from a societal perspective. Intervention costs, other healthcare costs, costs to patient and family, and productivity losses were included. The main outcomes were changes in the SF-36 physical component scale and quality-adjusted life-years. Changes were followed until 6 months after treatment. Uncertainty was estimated using nonparametric bootstrap analysis, cost-effectiveness acceptability curves and cost-effectiveness planes. Sensitivity analyses were performed to check robustness of findings. RESULTS: Forty-six patients were randomized and thirty-eight completed the study. Over 6 months, EXP resulted in greater improvement in physical health-related quality of life and quality-adjusted life-years than PPT. Despite higher initial treatment costs, EXP showed a tendency to reduce all costs compared with PPT; healthcare costs were significantly reduced. Furthermore, the cost-effectiveness planes were in favor of EXP. Sensitivity analyses, for different program costs and complete cases only, confirmed robustness of these findings. CONCLUSIONS: EXP, a cognitive-behavioral treatment, seems more cost-effective than PPT in CRPS patients with pain-related fear. The initial higher costs for EXP are offset by a long-term reduction of costs for healthcare use, and a tendency to lower work absenteeism and reduced societal costs. Due to low sample sizes, replication of findings is required to confirm results.

Classical Conditioning Fails to Elicit Allodynia in an Experimental Study with Healthy Humans.

OBJECTIVE: Associative learning has been proposed as a mechanism behind the persistence of pain after tissue healing. The simultaneous occurrence of nociceptive and non-nociceptive input during acute injury mimics the pairings thought to drive classical conditioning effects. However, empirical evidence for classically conditioned allodynia is lacking. We aimed to manipulate pain thresholds with a classical conditioning procedure that used non-nociceptive somatosensory stimuli as conditioned stimuli (CS) and nociceptive stimuli as unconditioned stimuli. We also explored the influence of gender, depression, anxiety, negative affect, and pain catastrophizing on the main manipulation. DESIGN: Thirty-four healthy humans participated in a differential classical conditioning procedure that used vibrotactile stimulations at two different locations as CS. In an acquisition phase, CS+ was paired with painful thermal stimulation, and CS- with nonpainful thermal stimulation. Heat pain threshold was assessed during paired heat-CS trials before and after acquisition. A 2 (time: 1 and 2) x 2 (condition: CS+ and CS-) repeated-measures analysis of variance compared pain thresholds before and after acquisition. Exploratory analyses explored the influence of gender, depression, anxiety, negative affect, and pain catastrophizing. Postexperiment questions investigated participants' awareness of the contingencies employed. RESULTS: The classical conditioning procedure did not alter pain thresholds. Exploratory analyses did not reveal any influence of individual differences. Thirty of the 34 participants were unaware of the contingencies between stimuli. CONCLUSIONS: The results of this study provide no evidence that allodynia can be induced in healthy humans using a classical conditioning procedure with simultaneous timing.

Learned Fear of Gastrointestinal Sensations in Healthy Adults.

BACKGROUND & AIMS: Gastrointestinal symptom-specific fear and anxiety are important determinants of gastrointestinal symptom perception. We studied learning of fear toward innocuous gastrointestinal sensations as a putative mechanism in the development of gastrointestinal symptom-specific fear and anxiety. METHODS: Fifty-two healthy subjects (26 women) received 2 types of esophageal balloon distention at a perceptible but nonpainful intensity (conditioned stimulus [CS], the innocuous sensation) and at a painful intensity (unconditioned stimulus [US]). Subjects were assigned randomly to 1 of 2 groups. During the learning phase, the innocuous CS preceded the painful US in the experimental group (n = 26). In the control group (n = 26), on the contrary, the US never followed the CS directly. During a subsequent extinction phase, both groups received only CS distention-the painful US was no longer administered. Indexes of fear learning toward the innocuous CS distention included the skin conductance response, fear-potentiated startle (measured by the eye-blink electromyogram), and self-reported expectancy of the US. RESULTS: During the learning phase, only the experimental group learned to fear the innocuous gastrointestinal CS, based on the increase in US expectancy (compared with the control group, P = .04), increased skin conductance response (compared with the control group, P = .03), and potentiated startle reflex (compared with the control group, P = .001) in response to the CS. The differences between the experimental and control groups in US expectancy and skin conductance, but not fear-potentiated startle, disappeared during the extinction phase. CONCLUSIONS: Fear toward innocuous gastrointestinal sensations can be established through associative learning in healthy human beings. This may be an important mechanism in the development of fear of gastrointestinal symptoms, implicated in the pathophysiology of functional gastrointestinal disorders.

Influence of Interoceptive Fear Learning on Visceral Perception.

OBJECTIVES: Interoceptive fear learning and generalization have been hypothesized to play a key role in unexplained abdominal and esophageal pain in patients with functional gastrointestinal disorders. However, there is no experimental evidence demonstrating that fear learning and generalization to visceral sensations can be established in humans and alter visceral perception. METHODS: In a novel fear learning-generalization paradigm, an innocuous esophageal balloon distension served as conditioned stimulus (CS), and distensions at three different pressure levels around the pain detection threshold were used as generalization stimuli. During fear learning, the CS was paired with a painful electrical stimulus (unconditioned stimulus) in the conditioning group (n = 30), whereas in the control group (n = 30), the unconditioned stimulus was delivered alone. Before and after fear learning, visceral perception thresholds for first sensation, discomfort, and pain and visceral discrimination sensitivity were assessed. RESULTS: Fear learning was established in the conditioning group only (potentiated eye-blink startle to the CS (t(464.06) = 3.17, p = .002), and fear generalization to other stimulus intensities was observed (t(469.12) = 2.97, p = .003; t(464.29) = 4.17, p < .001). The thresholds for first sensation habituated in the control group, whereas it remained constant in the conditioning group (F(1,43) = 9.77, p = .003). CONCLUSIONS: These data show that fear learning using visceral stimuli induces fear generalization and influences visceral perception. These findings support the idea that in functional gastrointestinal disorder, fear learning and generalization can foster gastrointestinal-specific anxiety and contribute to visceral hypersensitivity.

Global and Situational Relationship Satisfaction Moderate the Effect of Threat on Pain in Couples.

OBJECTIVE: The aim of this study was to test the hypothesis that greater global and situational relationship satisfaction would reduce the negative impact of threatening information on acute pain. DESIGN: An experimental design was used to manipulate threat and elicit acute pain via a cold pressor task. SETTING: The study was completed in a research laboratory at a large urban university in the Midwestern USA. SUBJECTS: Participants were 134 couples, in which at least one individual was an undergraduate student. METHODS: After administration of a global relationship satisfaction measure, couples were randomly assigned to either receive high or low threatening information about the painful task. Following the threat manipulation, couples discussed the upcoming task and rated their satisfaction with the interaction (i.e., situational relationship satisfaction). The designated pain participant then completed the painful task alone. RESULTS: The threat manipulation altered couples' perceived threat of pain. Situational relationship satisfaction moderated the effect of threat on pain trajectories such that situational relationship satisfaction predicted less pain intensity at an earlier point in the task for the low threat condition than the high threat condition. Greater global relationship satisfaction predicted greater likelihood of task completion among those in the low threat condition, whereas it was unrelated to task completion in the high threat condition. Greater global relationship satisfaction also predicted lower pain intensity throughout the task. CONCLUSIONS: These findings demonstrate that the interpersonal context is independently related to acute pain and may also alter the effect of threatening information on acute pain.

Can Pain or Hyperalgesia Be a Classically Conditioned Response in Humans? A Systematic Review and Meta-Analysis.

BACKGROUND: Clinical scenarios of repeated pain usually involve both nociceptive and non-nociceptive input. It is likely that associations between these stimuli are learned over time. Such learning may underlie subsequent amplification of pain, or evocation of pain in the absence of nociception. METHODS: We undertook a systematic review and meta-analysis to evaluate the evidence that allodynia or hyperalgesia can be a classically conditioned response. A sensitive search of the literature covered Medline, Embase, CINAHL, AMED, PubMed, Scopus, PsycArticles, PsycINFO, Cochrane Library, and Web of Science. Additional studies were identified by contacting experts and searching published reviews. Two reviewers independently assessed studies for inclusion, evaluated risk of bias, and extracted data. Studies were included if they aimed to elicit or amplify pain using a classical conditioning procedure in healthy, adult humans. Studies were excluded if they did not distinguish between classical conditioning and explicit verbal suggestion as learning sources, or did not use experiential learning. RESULTS: Thirteen studies, with varying risk of bias, were included. Ten studies evaluated classically conditioned hyperalgesia: nine found hyperalgesia; one did not. Pooled effects (n = 8 with full data) showed a significant pain increase after conditioning (mean difference of 7.40 [95%CI: 4.00-10.80] on a 0-100 pain scale). Three studies evaluated conditioned allodynia and found conflicting results. CONCLUSION: The existing literature suggests that classical conditioning can amplify pain. No conclusions can be drawn about whether or not classical conditioning can elicit pain. Rigorous experimental conditioning studies with nociceptive unconditioned stimuli are needed to fill this gap in knowledge.

Effectiveness of a home-based cognitive behavioral program to manage concerns about falls in community-dwelling, frail older people: results of a randomized controlled trial.

BACKGROUND: Concerns about falls are common among older people. These concerns, also referred to as fear of falling, can have serious physical and psychosocial consequences, such as functional decline, increased risk of falls, activity restriction, and lower social participation. Although cognitive behavioral group programs to reduce concerns about falls are available, no home-based approaches for older people with health problems, who may not be able to attend such group programs are available yet. The aim of this study was to assess the effectiveness of a home-based cognitive behavioral program on concerns about falls, in frail, older people living in the community. METHODS: In a randomized controlled trial in the Netherlands, 389 people aged 70 years and older, in fair or poor perceived health, who reported at least some concerns about falls and related activity avoidance were allocated to a control (n = 195) or intervention group (n = 194). The intervention was a home-based, cognitive behavioral program consisting of seven sessions including three home visits and four telephone contacts. The program aims to instill adaptive and realistic views about fall risks via cognitive restructuring and to increase activity and safe behavior using goal setting and action planning and was facilitated by community nurses. Control group participants received usual care. Outcomes at 5 and 12 months follow-up were concerns about falls, activity avoidance due to concerns about falls, disability and falls. RESULTS: At 12 months, the intervention group showed significant lower levels of concerns about falls compared to the control group. Furthermore, significant reductions in activity avoidance, disability and indoor falls were identified in the intervention group compared with the control group. Effect sizes were small to medium. No significant difference in total number of falls was noted between the groups. CONCLUSIONS: The home-based, cognitive behavioral program significantly reduces concerns about falls, related activity avoidance, disability and indoor falls in community-living, frail older people. The program may prolong independent living and provides an alternative for those people who are not able or willing to attend group programs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01358032. Registered 17 May 2011.

The effect of threat information on acquisition, extinction, and reinstatement of experimentally conditioned fear of movement-related pain.

OBJECTIVE: The experiential acquisition of pain-related fear has been demonstrated by pairing a painful electrocutaneous stimulus pain-US; unconditioned pain stimulus) with one movement (CS+; conditioned stimulus) but not with another (CS-). However, it is expected that during acquisition through direct experience, pain-related fear can be intensified or weakened by verbally/visually transmitted information about the pain and its meaning. METHOD: Participants received threatening information (US-inflation), safety information (US-deflation), or no information about the pain-US (US-same). Additionally, we measured return of fear after a reinstatement procedure: two unsignaled pain-USs were presented in the experimental groups, but not in the control groups. RESULTS: We replicated the acquisition and extinction of experimentally induced fear of movement-related pain in healthy subjects both in the verbal reports and the eye-blink startle measures. Two reinstating pain-US presentations led to a differential return of self-reported fear and a nondifferential return of fear in the eye-blink startle responses. Although, we failed to find an effect of verbal/visual information regarding the meaning of the pain-US on the acquisition, extinction, or reinstatement of pain-related fear, we did observe a pain sensitization effect over time suggesting that our threat manipulation induced an increase of perceived threat in all groups. CONCLUSION: The results suggest that our threat manipulation might not have worked or that it was not sensitive enough to yield group-specific effects. We replicated acquisition, extinction, and return of experimentally conditioned fear of movement-related pain, but the threat manipulation failed to generate any additional effects.

Is exposure in vivo cost-effective for chronic low back pain? A trial-based economic evaluation.

BACKGROUND: Back pain is one of the most expensive health complaints. Comparing the economic aspects of back pain interventions may therefore contribute to a more efficient use of available resources. This study reports on a long-term cost-effectiveness analysis (CEA) and cost-utility analysis (CUA) of two treatments as viewed from a societal perspective: 1) exposure in vivo treatment (EXP), a recently developed cognitive behavioral treatment for patients with chronic low back pain who have elevated pain-related fear and 2) the more commonly used graded activity (GA) treatment. METHODS: Sixty-two patients with non-specific chronic low back pain received either EXP or GA. Primary data were collected at four participating treatment centers in the Netherlands. Primary outcomes were self-reported disability (for the CEA) and quality-adjusted life years (for the CUA). Program costs, health care utilization, patient and family costs, and production losses were measured by analyzing therapy records and cost diaries. Data was gathered before, during, and after treatment, and at 6 and 12 months after treatment. Non-parametric bootstrap analyses were used to quantify the uncertainty concerning the cost-effectiveness ratio. In addition, cost-effectiveness planes and cost-effectiveness acceptability curves were performed. RESULTS: EXP showed a tendency to reduce disability, increase quality adjusted life years and decrease costs compared to GA. The incremental cost-effectiveness ratios of both the CEA and CUA are in favor of EXP. CONCLUSIONS: Based on these results, implementing EXP for this group of patients seems to be the best decision. TRIAL REGISTRATION: ISRCTN88087718.