Individual Patterns and Temporal Trajectories of Changes in Fear and Pain during Exposure In Vivo: A Multiple Single-Case Experimental Design in Patients with Chronic Pain.

Exposure in vivo (EXP) is an effective treatment to reduce pain-related fear and disability in chronic pain populations. Yet, it remains unclear how reductions in fear and pain relate to each other. This single-case experimental design study attempted to identify patterns in the individual responses to EXP and to unravel temporal trajectories of fear and pain. Daily diaries were completed before, during and after EXP. Multilevel modelling analyses were performed to evaluate the overall effect. Temporal effects were scrutinized by individual regression analyses and determination of the time to reach a minimal clinically important difference. Furthermore, individual graphs were visually inspected for potential patterns. Twenty patients with chronic low back pain and complex regional pain syndrome type I were included. On a group level, both fear and pain were reduced following EXP. Individually, fear was significantly reduced in 65% of the patients, while pain in only 20%. A decrease in fear was seen mostly in the first weeks, while pain levels reduced later or remained unchanged. Daily measurements provided rich data on temporal trajectories of reductions in fear and pain. Overall, reductions in fear preceded pain relief and seemed to be essential to achieve pain reductions.

Corticolimbic Circuitry in Chronic Pain Tracks Pain Intensity Relief Following Exposure In Vivo.

Background: A subset of patients with chronic pain who receive exposure in vivo (EXP) treatment experience clinically relevant relief of pain intensity. Although pain relief is not an explicit therapeutic target, it is important to understand how and why this concomitant effect occurs in some patients but not others. This longitudinal study therefore aimed to characterize brain plasticity as well as to explore pretreatment factors related to pain relief. Methods: Resting-state functional magnetic resonance imaging data were acquired in 30 patients with chronic pain. Twenty-three patients completed EXP, and 6-month follow-up data were available in 20 patients (magnetic resonance imaging data in 17 patients). Pain-free control data were acquired at two time points (n = 29, n = 21). Seed-based resting-state functional connectivity (rsFC) analyses were performed, with seeds in the amygdala, hippocampus, and nucleus accumbens. Results: Pain relief after EXP was highly variable, with 60% of patients reporting a clinically relevant improvement. Amygdala rsFC with the middle frontal gyrus decreased significantly over time in patients but was not associated with pain relief. In contrast, greater pain relief was associated with greater decreases over time in hippocampus rsFC with the precuneus, which was related to reductions in catastrophizing (EXP therapeutic target) as well. Greater pain relief was also associated with lower pretreatment rsFC between nucleus accumbens and postcentral gyrus. Conclusions: While changes in hippocampus rsFC were associated with pain relief after EXP, pretreatment nucleus accumbens rsFC showed potential prognostic value. Our findings further support the importance of corticolimbic circuitry in chronic pain, emphasizing its relation to pain relief and identifying potential underlying mechanisms and prognostic factors, warranting further testing in independent samples.

Exposure in vivo Induced Changes in Neural Circuitry for Pain-Related Fear: A Longitudinal fMRI Study in Chronic Low Back Pain.

Exposure in vivo (EXP) is a cognitive-behavioral treatment aimed at reducing pain-related fear in chronic pain, and has proven successful in reducing pain-related disability in patients with chronic low back pain (cLBP). The current longitudinal study aimed to reveal the neural correlates of changes in pain-related fear as a result of EXP. Twenty-three patients with cLBP were included in this study. Patients with cLBP underwent MRI scanning pre-treatment (pre-EXP), post-treatment (post-EXP), and 6 months after end of treatment (FU-EXP). Pain-free controls were scanned at two time points. In the scanner, participants were presented with pictures involving back-related movements, evoking pain-related fear in patients. Pre-treatment, functional MRI revealed increased activation in right posterior insula and increased deactivation in medial prefrontal cortex (mPFC) in patients compared to controls. Post-treatment, patients reported reduced fear and pre-EXP group differences were no longer present. Contrasting pre- to post- and FU-EXP in patients revealed that stimulus-evoked neural responses changed in sensorimotor as well as cognitive/affective brain regions. Lastly, exploratory analyses revealed a tendency toward an association between changes in neural activation and changes in fear ratings, including the hippocampus and temporal lobe (pre- to post-EXP changes), and mPFC and posterior cingulate cortex (pre- to FU-EXP changes). Taken together, we show evidence that neural circuitry for pain-related fear is modulated by EXP, and that changes are associated with self-reported decreases in pain-related fear.

Living with painful diabetic neuropathy: insights from focus groups into fears and coping strategies.

OBJECTIVE: Painful diabetic neuropathy (PDN) is known to negatively affect quality of life. Being physically active is a crucial part of successful diabetes self-management, but regimen adherence is often low. Coping strategies and fears have shown to be related to less physical activity (PA). The aim of the present study was to obtain more in-depth information on psychological risk factors leading to less PA in persons with PDN. DESIGN: Three semi-structured focus group interviews were conducted with a representative sample of persons with PDN (N = 12). Data were transcribed verbatim and analysed using a hybrid method of thematic analyses and a grounded theory approach. MAIN OUTCOME MEASURES: Fears and coping strategies related to PA in persons with PDN. RESULTS: Several specific fears were identified; fear of hypoglycaemia, fear of pain increase, fear of total exhaustion, fear of physical injury, fear of falling, fear of loss of identity, and fear of negative evaluation by others. To cope with these fears, avoidance, remaining active, cognitive distraction, and acceptance strategies were described. CONCLUSION: In persons with PDN, diabetes-related fears and pain-related fears play a role in less engagement in PA, indicating the need for new methods for improving self-management in persons with PDN.

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.

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.

Reduction of pain-related fear and increased function and participation in work-related upper extremity pain (WRUEP): effects of exposure in vivo.

There is increasing evidence that pain-related fear influences the development and maintenance of pain disability, presumably mediated through the fear-related avoidance of valued activities. Individually tailored graded exposure in vivo (GEXP) has been demonstrated to reduce pain-related fear and increase functional abilities in patients with chronic low back pain, neck pain, and complex regional pain syndrome. The current study aimed to test whether these effects generalize towards patients with work-related upper extremity pain. A sequential replicated and randomized single-case experimental phase design with multiple measurements was used. Within each participant, GEXP was compared to a no-treatment baseline period and a no-treatment 6-month follow-up period. Eight patients who reported a high level of pain-related fear were included in the study. Daily changes in pain catastrophizing, pain-related fear, and pain intensity were assessed using a diary, and subjected to randomization tests. Before the start of the baseline period, just after GEXP, and at 6-month follow-up, clinically relevant changes of pain catastrophizing, pain-related fear, perceived harmfulness of physical activity, pain disability, and participation/autonomy were verified. When GEXP was introduced, levels of pain catastrophizing and pain-related fear decreased significantly. Clinically relevant improvements were observed for pain disability, perceived participation, and autonomy. These favourable changes were maintained until 6-month follow-up. The findings of the current study underscore the external validity of a cognitive-behavioural GEXP treatment for patients with chronic pain reporting increased pain-related fear.

Pain-related fear, perceived harmfulness of activities, and functional limitations in complex regional pain syndrome type I.

UNLABELLED: Numerous studies have shown that pain-related fear is one of the strongest predictors of pain disability in patients with chronic musculoskeletal pain, and there is evidence that the reduction of pain-related fear through an exposure treatment can be associated with restoration of functional abilities in patients with complex regional pain syndrome type I (CRPS-I). These findings suggest that pain-related fear may be associated with functional limitations in neuropathic pain as well. The aim of the current study was to test whether the debilitating role of pain-related fear generalizes to patients with CRPS-I. The results of 2 studies are presented. Study I includes a sample of patients with early CRPS-I referred to an outpatient pain clinic. In Study II, patients with chronic CRPS who are members of a patients' association were invited to participate. The results show that in early CRPS-I, pain severity but not fear of movement/(re)injury as measured with the Tampa Scale for Kinesiophobia was related to functional limitations. In patients with chronic CRPS-I, however, perceived harmfulness of activities as measured with the pictorial assessment method significantly predicted functional limitations beyond and above the contribution of pain severity. Not fear of movement/(re)injury in general, but the perceived harmfulness of activities appears a key factor that might be addressed more systematically in the clinical assessment of patients with CRPS-I. These results support the idea that pain-related fear might be a promising concept in the understanding of pain disability in patients with neuropathic pain. PERSPECTIVE: This is the first study showing that perceived harmfulness of activities contribute to the functional limitations in CRPS-I. The current findings may help clinicians customizing cognitive-behavioral treatments for patients with chronic neuropathic pain.

Fear reduction in patients with chronic pain: a learning theory perspective.

Acute pain informs the individual that there is an imminent threat of body damage, and is associated with the urge to escape and avoid. Fear learning takes place when neutral stimuli receive the propensity to predict the occurrence of pain, and when defensive responses are initiated in anticipation of potential threats to the integrity of the body. Fear-avoidance models have been put forward featuring the role of individual differences in catastrophic interpretations of pain in the modulation of learning and avoidance. Based on extensive literature on fear reduction in anxiety disorders; cognitive-behavioral treatments have been developed and applied to patients with chronic pain reporting substantial pain-related fear. In this article, we discuss mechanisms underlying the acquisition, the assessment and extinction of pain-related fear through the cognitive-behavioral treatment of pain-related fear. Finally, we provide a number of critical notes and directions for future research in the field of chronic pain and pain-related fear.

Reduction of pain-related fear and disability in post-traumatic neck pain: a replicated single-case experimental study of exposure in vivo.

UNLABELLED: For patients with acute post-traumatic neck pain (PTNP), pain-related fear has been identified as a potential predictor of chronic disability. If such is the case, fear reduction should enhance the prevention of further pain disability and distress after traumatic neck pain disability. However, exposure-based treatments have not been tested in patients with PTNP. Using a replicated single-case crossover phase design with multiple measurements, this study examined whether the validity of a graded exposure in vivo, as compared with usual graded activity, extends to PTNP. Eight patients who reported substantial pain-related fear were included in the study. Daily changes in pain intensity, pain-related fear, pain catastrophizing, and activity goal achievement were assessed. Before and after each intervention, and at 6-month follow-up, standardized questionnaires of pain-related fear and pain disability were administered, and, to quantify daily physical activity level, patients carried an ambulatory activity monitor. The results showed decreasing levels of self-reported pain-related fear, pain intensity, disability, and improvements in physical activity level only when graded exposure in vivo was introduced, and not in the graded activity condition. The results are discussed in the context of the search for customized treatments for PTNP. PERSPECTIVE: This is the first study showing that the effects of graded exposure in vivo generalize to patients with chronic PTNP reporting elevated levels of pain-related fear. This could help clinicians to customize treatments for PTNP.

Exposure in vivo versus operant graded activity in chronic low back pain patients: results of a randomized controlled trial.

Since pain-related fear may contribute to the development and maintenance of chronic low back pain (CLBP), an exposure in vivo treatment (EXP) was developed for CLBP patients. We examined the effectiveness as well as specific mediating mechanisms of EXP versus operant graded activity (GA) directly and 6 months post-treatment in a multi-centre randomized controlled trial. In total, 85 patients suffering from disabling non-specific CLBP reporting at least moderate pain-related fear were randomly allocated to EXP or GA. It was demonstrated that EXP, despite excelling in diminishing pain catastrophizing and perceived harmfulness of activities, was equally effective as GA in improving functional disability and main complaints, although the group difference almost reached statistical significance favouring EXP. Both treatment conditions did not differ in pain intensity and daily activity levels either. Nor was EXP superior to GA in the subgroup of highly fearful patients. Irrespective of treatment, approximately half the patients reported clinically relevant improvements in main complaints and functional disability, although for the latter outcome the group difference was almost significant favouring EXP. Furthermore, the effect of EXP relative to GA on functional disability and main complaints was mediated by decreases in catastrophizing and perceived harmfulness of activities. In sum, this study demonstrates that up to 6 months after treatment EXP is an effective treatment, but not more effective than GA, in moderately to highly fearful CLBP patients, although its superiority in altering pain catastrophizing and perceived harmfulness of activities is clearly established. Possible explanations for these findings are discussed.

Reduction of pain-related fear in complex regional pain syndrome type I: the application of graded exposure in vivo.

Fear of (re)injury/movement has been identified as a potential predictor of chronic disability in complex regional pain syndrome type I (CRPS-I). In order to reduce pain-related fears and pain disability, graded exposure in vivo (GEXP) is likely to be an appropriate treatment. Indeed, there is evidence that in chronic pain patients reporting substantial fear of (re)injury/movement, GEXP is successful in reducing pain disability. However, the efficacy of exposure-based protocols in the treatment of CRPS-I patients for reducing pain disability has not been tested. The main research question of this study was whether the reduction of pain-related fear through GEXP also resulted in a decrease of disability in a subgroup of patients with CRPS-I who report substantial pain-related fear. A single-case experimental ABCD-design was used with random determination of the start of the intervention. Eight patients with CRPS-I were included in the study. To assess daily changes in pain intensity, pain-related fear, pain catastrophizing, and activity goal achievement, a diary was used. Standardized questionnaires of pain-related fear, pain disability, and self-reported signs and symptoms of CRPS-I were administered before and after each intervention, and at 6-month follow-up. The current study supports a GEXP approach to chronic CRPS-I. The GEXP was successful in decreasing levels of self-reported pain-related fear, pain intensity, disability, and physiological signs and symptoms. These results support the hypothesis that the meaning people attach to a noxious stimulus influences its experienced painfulness, and that GEXP activates cortical networks and reconciles motor output and sensory feedback.

Fear of movement/(re)injury in chronic low back pain: education or exposure in vivo as mediator to fear reduction?

Clinical research of graded exposure in vivo with behavioral experiments in patients with chronic low back pain who reported fear of movement/(re)injury shows abrupt changes in self-reported pain-related fears and cognitions. The abrupt changes are more characteristics of insight learning rather than the usual gradual progression of trial and error learning. The educational session at the start of the exposure might have contributed to this insight. The current study examines the contribution of education and graded exposure versus graded activity in the reduction of pain-related fear and associated disability and physical activity. Six consecutive patients with chronic low back pain who reported substantial fear of movement/(re)injury were included in the study. After a no-treatment baseline measurement period, all the patients received a single educational session, followed again by a no-treatment period. Patients were then randomly assigned to either a graded exposure with behavioral experiments or an operant graded activity program. A diary was used to assess daily changes in pain intensity, pain-related fear, pain catastrophizing, and activity goal achievement. Standardized questionnaires of pain-related fear, pain vigilance, pain intensity, and pain disability were administered before and after each intervention and at the 6-month follow-up. An activity monitor was carried at baseline, during the interventions, and 1 week at 6-month follow-up. Randomization tests of the daily measures showed that improvements in pain-related fear and catastrophizing occurred after the education was introduced. The results also showed a further improvement when exposure in vivo followed the no-treatment period after the education and not during the operant graded activity program. Performance of relevant daily activities, however, were not affected by the educational session and improved significantly only in the exposure in vivo condition. All improvements remained at half-year follow-up only in patients receiving the exposure in vivo. These patients also reported a significant decrease in pain intensity at follow-up.

Can pain-related fear be reduced? The application of cognitive-behavioural exposure in vivo.

Although cognitive-behavioural treatments of patients with chronic pain generally are reported to be effective, customization might increase their effectiveness. One possible way to customize treatment is to focus the intervention on the supposed mechanism underlying the transition from acute to chronic pain disability. Evidence is accumulating in support of the conjecture that pain-related fear and associated avoidance behaviours are crucial in the development and maintenance of chronic pain disability. It seems timely to apply this knowledge to the cognitive-behavioural management of chronic pain. Two studies are presented here. Study 1 concerns a secondary analysis of data gathered in a clinical trial that was aimed at the examination of the supplementary value of coping skills training when added to an operant-behavioural treatment in patients with chronic back pain. The results show that, compared with a waiting list control, an operant-behavioural treatment with or without pain-coping skills training produced very modest and clinically negligible decreases in pain-related fear. Study 2 presents the effects of more systematic exposure in vivo treatment with behavioural experiments in two single patients reporting substantial pain-related fear. Randomization tests for AB designs revealed dramatic changes in pain-related fear and pain catastrophizing. In both cases, pain intensity also decreased significantly, but at a slower pace. Differences before and after treatment revealed clinically significant improvements in pain vigilance and pain disability.