The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms.

BACKGROUND: Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) often present with a range of flu-like symptoms resembling sickness behavior as well as widespread pain and concentration deficits. The aim of this study was to explore the association between inflammatory markers previously shown to be related to fatigue severity in ME/CFS and common ME/CFS symptoms post-exertional fatigue, impaired cognitive processing, musculoskeletal pain and recurrent flu-like symptoms, and the moderating effect of sex on these associations. METHODS: 53 adult patients diagnosed with ME/CFS at a specialist clinic were included in the study. Fasting blood plasma was analyzed using the Olink Proseek Multiplex Inflammation panel (ß-NGF, CCL11, CXCL1, CXCL10, IL-6, IL-7, IL-8, IL-10, IL-18, TGF-α, TGF-ß-1 and SCF) and BioRad Human Cytokine Type 1 assay (TNF-α). Participants rated the average severity of symptoms (0-10) based on the 2011 International Consensus Criteria of ME/CFS during a structured clinical interview. Associations between inflammatory markers and symptom severity were analyzed using bivariate correlations and moderated regression analyses bootstrapped with 5000 repetitions. RESULTS AND CONCLUSIONS: Only ß-NGF was associated with the fatigue severity measure. However, higher levels of CCL11, CXCL10, IL-7, TNF-α and TGF-ß-1 were significantly associated with higher levels of impaired cognitive processing and musculoskeletal pain, and sex was a significant moderator for CXCL10, IL-7 and TGF-ß-1. Future studies should investigate the relationship between inflammatory markers and key symptoms in ME/CFS in a longitudinal design in order to explore if and for whom low-grade inflammation may contribute to illness development.

Patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain report similar level of sickness behavior as individuals injected with bacterial endotoxin at peak inflammation.

Background: Chronic sickness behavior is implicated in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain but the level of subjective sickness behavior in these conditions has not been investigated or compared to other clinical and non-clinical samples, or to the level in experimental inflammation. Furthermore, the relationship between sickness behavior and self-rated health and functioning is not known in patients with ME/CFS and chronic pain. The aim of the present study was to investigate how sickness behavior in patients with chronic conditions differs from that in individuals with experimental acute sickness, primary care patients, the general population and healthy subjects. In addition, we wanted to explore how sickness behavior is related to self-rated health and health-related functioning. Methods: Sickness behavior was quantified using the sickness questionnaire (SicknessQ). Self-ratings were collected at one time-point in 6 different samples. Levels of sickness behavior in patients with ME/CFS (n â€‹= â€‹38) and patients with chronic pain (n â€‹= â€‹190) were compared to healthy subjects with lipopolysaccharide(LPS)-induced inflammation (n â€‹= â€‹29), primary care patients (n â€‹= â€‹163), individuals from the general population (n â€‹= â€‹155) and healthy subjects (n â€‹= â€‹48), using linear regression. Correlations and moderated regression analyses were used to investigate associations between sickness behavior and self-rated health and health-related functioning in ME/CFS, chronic pain and the general population. Results: LPS-injected individuals (M â€‹= â€‹16.3), patients with ME/CFS (M â€‹= â€‹16.1), chronic pain (M â€‹= â€‹16.1) and primary care patients (M â€‹= â€‹10.7) reported significantly higher SicknessQ scores than individuals from the general population (M â€‹= â€‹5.4) and healthy subjects (M â€‹= â€‹3.6) all p's â€‹< â€‹0.001). In turn, LPS-injected individuals, patients with ME/CFS and chronic pain reported significantly higher SicknessQ scores than primary care patients (p's â€‹< â€‹0.01). Higher levels of sickness behavior were associated with poorer self-rated health and health-related functioning (p's â€‹< â€‹0.01), but less so in patients with ME/CFS and chronic pain than in individuals from the general population. Conclusions: Patients with ME/CFS and chronic pain report similar high levels of sickness behavior; higher than primary care patients, and comparable to levels in experimental inflammation. Further study of sickness behavior in ME/CFS and chronic pain populations is warranted as immune-to-brain interactions and sickness behavior may be of importance for functioning as well as in core pathophysiological processes in subsets of patients.

Low-grade inflammation may moderate the effect of behavioral treatment for chronic pain in adults.

The purpose of the present pilot study was to explore the moderating role of basal inflammation on the effects of behavioral pain treatment in 41 patients with long-standing pain. Baseline pro-inflammatory status moderated behavioral treatment outcomes: higher pre-treatment levels of Tumor Necrosis Factor (TNF)-α and Interleukin (IL)-6 were related to less improvement in pain intensity, psychological inflexibility and in mental health-related quality of life. The treatment outcomes improved in the subgroup that had low levels of pro-inflammatory cytokines at baseline, while the subjects with higher pro-inflammatory status did not. Altogether, results indicate that low-grade inflammation may influence the behavioral treatment outcomes and provide a possible explanation of the heterogeneity in treatment response.

Exploring Changes in Valued Action in the Presence of Chronic Debilitating Pain in Acceptance and Commitment Therapy for Youth - A Single-Subject Design Study.

Objective: The objective of the study was to improve the understanding of processes of change in Acceptance and Commitment Therapy for youth with chronic debilitating pain by exploring the relation between individual change patterns in pain intensity and valued activities. Method: A single-subject design across three adolescents suffering from longstanding debilitating pain was utilized. Pain intensity and participation in valued activities were rated daily. Visual analysis of the graphed data was performed to evaluate the effects of the intervention, and the relationship between pain intensity and values-based activity. Results: The graphed data illustrated that pain levels did not decrease from the baseline period to the follow-up period. In contrast, compared to baseline ratings values oriented behaviors increased from the start of treatment to the follow-up period. Conclusion: Results illustrate that increases in values-based behavior may occur without corresponding decreases in pain, and warrant further research on change processes in ACT for youth suffering from chronic pain.

Efficacy and Cost-effectiveness of Acceptance and Commitment Therapy and Applied Relaxation for Longstanding Pain: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: To date, few studies have compared Acceptance and Commitment Therapy (ACT) for longstanding pain with established treatments. Only 1 study has evaluated the cost-effectiveness of ACT. The aim of the current study was to evaluate the efficacy and cost-effectiveness of ACT and applied relaxation (AR) for adults with unspecific, longstanding pain. MATERIALS AND METHODS: On the basis of the inclusion criteria 60 consecutive patients received 12 weekly group sessions of ACT or AR. Data were collected pretreatment, midtreatment, and posttreatment, as well as at 3- and 6-month follow-up. Growth curve modeling was used to analyze treatment effects on pain disability, pain intensity, health-related quality of life (physical domain), anxiety, depression, and acceptance. RESULTS: Significant improvements were seen across conditions (pretreatment to follow-up assessment) on all outcome measures. Pain disability decreased significantly in ACT relative to AR from preassessment to postassessment. A corresponding decrease in pain disability was seen in AR between postassessment and 6-month follow-up. Pain acceptance increased only in ACT, and this effect was maintained at 6-month follow-up. Approximately 20% of the participants achieved clinically significant change after treatment. Health economic analyses showed that ACT was more cost-effective than AR at post and 3-month follow-up assessment, but not at 6-month follow-up. DISCUSSION: More studies investigating moderators and mediators of change are needed. The present study is one of few that have evaluated the cost-effectiveness of ACT and AR and compared ACT with an established behavioral intervention, and the results provide additional support for behavioral interventions for longstanding pain.

Mediators of change in acceptance and commitment therapy for pediatric chronic pain.

Even though psychological interventions are well established in the treatment of pediatric chronic pain, there is a clear need for further development, especially with severely disabled patients. However, optimizing effectiveness in psychological treatments for pain requires clarification of the mechanisms of action. Studies addressing change processes are scarce, however, particularly in relation to pediatric chronic pain. Acceptance and Commitment Therapy (ACT), as an extension of traditional cognitive behavior therapy, is essentially aimed at improving functioning by increasing the ability to act effectively in the presence of pain and distress, that is, psychological flexibility. ACT has shown promising results for both adult and pediatric chronic pain. In the present study, the mediators of change in an ACT-oriented treatment for pediatric chronic pain were examined using a bootstrapped cross product of coefficients approach. Pain interference and depression were used as outcome variables. Six different variables relevant to theories underlying ACT and cognitive behavior therapy were included in the analyses as possible mediators of change: pain impairment beliefs, pain reactivity, self-efficacy, kinesiophobia, catastrophizing, and pain intensity. Results illustrated that pain impairment beliefs and pain reactivity were the only variables that significantly mediated the differential effects of treatment on outcomes at follow-up. Also, these 2 mediators were shown to independently predict effects in outcome variables at follow-up while controlling for earlier effects in outcome, but only for the ACT condition. Although tentative, the pattern of results suggests that variables consistent with psychological flexibility mediate the effects of ACT-based interventions to improve functioning in patients with chronic debilitating pain.

Psychological flexibility as a mediator of improvement in Acceptance and Commitment Therapy for patients with chronic pain following whiplash.

Cognitive behavior therapy (CBT) has made important contributions to chronic pain management, but the process by which it is effective is not clear. Recently, strong arguments have been raised concerning the need for theory driven research to e.g. identify mechanisms of change in CBT and enhance the effectiveness of this type of treatment. However, the number of studies addressing these issues is still relatively scarce. Furthermore, the arrival of varieties of CBT with seemingly different process targets increases the need for such information. The present study explored the processes of change in a previously reported successful randomized controlled trial evaluating the effectiveness of an exposure-based form of behavioral and cognitive therapy, Acceptance and Commitment Therapy (ACT), on improvement in pain-related disability and life satisfaction for patients suffering from whiplash-associated disorder (WAD). Several process variables relevant to theories underlying traditional CBT were included: pain, distress, kinesiophobia, self-efficacy, and the process primarily targeted by ACT: psychological inflexibility. Mediation analyses were performed using a non-parametric cross-product of the coefficients approach. Results illustrated that pain intensity, anxiety, depression, kinesiophobia, and self-efficacy did not have significant mediating effects on the dependent variables. In contrast, significant indirect effects were seen for psychological inflexibility on pain-related disability (pre- to post-change scores) and life satisfaction (pre- to post; pre- to 4-month follow-up change scores). Although tentative, these results support the mediating role of psychological inflexibility in ACT-oriented interventions aimed at improving functioning and life satisfaction in people with chronic pain.

The Psychological Inflexibility in Pain Scale (PIPS)--statistical properties and model fit of an instrument to assess change processes in pain related disability.

Recent developments within CBT have emphasized acceptance rather than control of pain and distress in treatments aimed at improving functioning and life quality, but there is still a lack of reliable and valid instruments to assess relevant processes in such interventions. The Psychological Inflexibility in Pain Scale (PIPS) was developed to assess target variables in exposure and acceptance oriented treatments. A preliminary validation study resulted in a two-factor solution with subscales for avoidance and cognitive fusion related to pain, showing satisfactory psychometric properties. This study sought to evaluate the instrument with 611 participants with whiplash associated disorders. Exploratory and confirmatory factor analyses supported a two-factor solution with 12 items which showed an acceptable model fit, adequate internal consistencies, and strong relations with criteria variables (e.g. disability and life satisfaction). The construct validity of the instrument was supported by high correlations with subscales from the Chronic Pain Acceptance Questionnaire (CPAQ) and the Tampa Scale of Kinesiophobia (TSK). Notably, hierarchical regression analyses illustrated that PIPS explained more variance than TSK in pain, disability, life satisfaction and depression. Furthermore, PIPS was found to mediate the relationship between e.g. pain and disability, suggesting the usefulness of PIPS as a process measure in treatments of people with chronic pain. Thus, it is argued that this 12-item version of PIPS may be used to explore the importance of psychological in/flexibility in chronic pain and to analyse processes of change in exposure based interventions, as well as for clinicians in tailoring interventions for patients with chronic debilitating pain.

Evaluating the effectiveness of exposure and acceptance strategies to improve functioning and quality of life in longstanding pediatric pain--a randomized controlled trial.

Although several studies have illustrated the effectiveness of cognitive behavior therapy (CBT) on adult pain patients, there are few randomized controlled trials on children and adolescents. There is particularly a need for studies on pediatric patients who are severely disabled by longstanding pain syndromes. Acceptance and Commitment Therapy, as an extension of traditional CBT, focuses on improving functioning and quality of life by increasing the patient's ability to act effectively in concordance with personal values also in the presence of pain and distress. Following a pilot study, we sought to evaluate the effectiveness of an ACT-oriented intervention based on exposure and acceptance strategies and to compare this with a multidisciplinary treatment approach including amitriptyline (n=32). The ACT condition underwent a relatively brief treatment protocol of approximately 10 weekly sessions. Assessments were made before and immediately after treatment, as well as at 3.5 and 6.5 months follow-up. Prolonged treatment in the MDT group complicated comparisons between groups at follow-up assessments. Results showed substantial and sustained improvements for the ACT group. When follow-up assessments were included, ACT performed significantly better than MDT on perceived functional ability in relation to pain, pain intensity and to pain-related discomfort (intent-to-treat analyses). At post-treatment, significant differences in favor of the ACT condition were also seen in fear of re/injury or kinesiophobia, pain interference and in quality of life. Thus, results from the present study support previous findings and suggest the effectiveness of this ACT-oriented intervention for pediatric longstanding pain syndromes.

The Chronic Pain Acceptance Questionnaire (CPAQ)-further validation including a confirmatory factor analysis and a comparison with the Tampa Scale of Kinesiophobia.

Acceptance of pain and distress has lately appeared as an important factor in determining peoples' ability to restore functioning in the presence of chronic pain. Although treatments based on cognitive behaviour therapy are beginning to incorporate acceptance strategies, there is still a lack of reliable and valid instruments to assess relevant processes in such interventions. The Chronic Pain Acceptance Questionnaire (CPAQ) was originally constructed as part of the development of an acceptance oriented treatment approach for pain patients. A revised 20-item version of the instrument with two subscales has shown adequate reliability and validity. In the present study, a Swedish translation of CPAQ was evaluated with 611 participants reporting chronic pain and symptoms of whiplash associated disorders. This study sought to further assess the psychometric properties of the instrument and to investigate its relation to another important measure of pain adjustment, the Tampa Scale of Kinesiophobia. Due to low intercorrelations with other items, item 16 was excluded. Exploratory and confirmatory factor analyses supported the previously suggested two-factor solution. Furthermore, the internal consistencies were good for the subscales (activities engagement and pain willingness) as well as the total scale. Hierarchical regression analyses illustrated strong relations with criteria variables (e.g. disability and life satisfaction). In general, the activities engagement subscale contributed more than pain willingness to the prediction of criteria variables. Furthermore, results illustrated that CPAQ explained more variance than the Tampa Scale of Kinesiophobia in pain intensity, disability, life satisfaction, and depression.

Infants' and toddlers' remembering and forgetting of a stressful medical procedure.

OBJECTIVE: To examine whether a distressing medical procedure leaves lasting impressions in young children's memories. METHODS: Children 12- to 78-weeks old (N = 172) received inhalation treatment through a face mask or underwent other interventions at a pediatric emergency department. They were randomized to be presented with neutral cues and cues from the inhalation 1 week or 6 months after the target event. Children's reactions at cue presentation were scored from videotapes. RESULTS: Across the age span tested, children treated with inhalation showed higher distress than controls when presented with cues from inhalation 1 week, but not 6 months after target treatment. CONCLUSIONS: Stress during medical procedures in preverbal children may develop as a result of prior experience of such procedures. These memories typically seem to fade within 6 months.

Can exposure and acceptance strategies improve functioning and life satisfaction in people with chronic pain and whiplash-associated disorders (WAD)? A randomized controlled trial.

Although 14% to 42% of people with whiplash injuries end up with chronic debilitating pain, there is still a paucity of empirically supported treatments for this group of patients. In chronic pain management, there is increasing consensus regarding the importance of a behavioural medicine approach to symptoms and disability. Cognitive behaviour therapy has proven to be beneficial in the treatment of chronic pain. An approach that promotes acceptance of, or willingness to experience, pain and other associated negative private events (e.g. fear, anxiety, and fatigue) instead of reducing or controlling symptoms has received increasing attention. Although the empirical support for treatments emphasizing exposure and acceptance (such as acceptance and commitment therapy) is growing, there is clearly a need for more outcome studies, especially randomized controlled trials. In this study, participants (N = 21) with chronic pain and whiplash-associated disorders were recruited from a patient organization and randomized to either a treatment or a wait-list control condition. Both groups continued to receive treatment as usual. In the experimental condition, a learning theory framework was applied to the analysis and treatment. The intervention consisted of a 10-session protocol emphasizing values-based exposure and acceptance strategies to improve functioning and life satisfaction by increasing the participants' abilities to behave in accordance with values in the presence of interfering pain and distress (psychological flexibility). After treatment, significant differences in favor of the treatment group were seen in pain disability, life satisfaction, fear of movements, depression, and psychological inflexibility. No change for any of the groups was seen in pain intensity. Improvements in the treatment group were maintained at 7-month follow-up. The authors discuss implications of these findings and offer suggestions for further research in this area.

Spinal cord stimulation in adolescents with complex regional pain syndrome type I (CRPS-I).

Complex regional pain syndrome type I (CRPS-I) is not uncommon in children, particularly in adolescent girls. Most often, the condition involves a foot and is characterized by spontaneous pain, tactile allodynia and dysautonomic signs. There is usually a history of a minor, local trauma but sometimes no reasonable cause can be identified, and there are no signs of persistent tissue injury giving rise to ongoing nociception. Common analgesics are generally of no benefit, and the standard treatment includes sociopsychological support, physiotherapy, tricyclic antidepressants and antiepileptic drugs, sympathetic blocks (SB), and cognitive-behavioural therapy. For a minority of patients who prove to be resistant to such therapies, spinal cord stimulation (SCS) may be tried. The present study comprises seven girls, 11-14 years of age, presenting with severe, incapacitating and therapy-resistant CRPS-I, who were subjected to SCS. In two of them, percutaneous electrode implantation had to be performed in general anaesthesia. Trial stimulation was performed in all, but one. In two cases, it was not possible to produce paraesthesias that entirely covered the pain area. A pain relieving effect of SCS was usually not reported until after 1-2 weeks of trial stimulation. After another 2-6 weeks, pain alleviation was complete in five of the seven patients, one to eight years after the intervention. In one case, a local infection necessitated the removal of the electrode; nevertheless a few days of trial stimulation produced substantial pain relief that still persists. In four patients, the SCS use was gradually diminished and eventually the device could be removed. The favourable outcome in all seven cases with no or minor remaining symptoms and without severe recurrences illustrates that SCS may also be an efficient treatment in paediatric cases with exceptionally therapy resistant forms of CRPS I.

Avoidance and cognitive fusion--central components in pain related disability? Development and preliminary validation of the Psychological Inflexibility in Pain Scale (PIPS).

Acceptance of pain and other associated negative private experiences has received increasing attention in recent years. This approach is in stark contrast to the traditional approach of reducing or controlling symptoms of pain. The empirical support for treatments emphasizing exposure and acceptance, such as Acceptance and Commitment Therapy, is growing. However, to date, few instruments exist to assess the core processes in these types of treatments. This study describes the development and preliminary validation of the Psychological Inflexibility in Pain Scale. Principal components analysis (PCA) suggests a 2-factor solution with a total of 16 items measuring avoidance of pain and cognitive fusion with pain. Results also indicate adequate reliability and validity for the scale. Implications of these findings for clinical assessment, as well as for research on pain related disability, are discussed along with suggestions for further research in this area.

Exposure and acceptance in the rehabilitation of adolescents with idiopathic chronic pain - a pilot study.

For chronic pain of unclear origin (idiopathic), pharmacological therapy is often insufficient. Psychological treatment strategies have been developed and evaluated for adults with chronic pain. However, few such studies are seen with youths, and to date there is limited empirical evidence regarding the effectiveness of psychological treatment for generalized musculoskeletal pain syndromes in adolescents. Acceptance and commitment therapy (ACT) is a development of cognitive behaviour therapy emphasizing exposure and acceptance. In this pilot study, 14 adolescents referred to the pain treatment service due to chronic debilitating pain were treated using an ACT-based approach. It was hypothesized that avoidance of pain and related stimuli was central to the disability seen among these patients, and that exposure and acceptance strategies could increase functioning and decrease pain. In contrast to emphasizing reductions in pain and distress, the treatment objective was to improve functioning by increasing the patient's ability to act in line with personal values in the presence of negative thoughts, emotions or bodily sensations. Following treatment, and retained at 3- and 6-month follow-up, improvements in functional ability, school attendance, catastrophizing and pain (i.e., intensity and interference) were seen. The outcome of this pilot study indicates that exposure and acceptance can been useful in the rehabilitation of adolescents with chronic debilitating pain. Randomized controlled studies are needed to empirically evaluate the effectiveness of this approach.

Sensory and affective components of pain as recorded with the Pain-O-Meter (POM) among children with acute and chronic pain.

AIM: To explore the usefulness of the Pain-O-Meter sensory and affective words scale (POM-WDS) with regard to whether children aged 6-16 who suffer from chronic and acute pain know the words and what words they chose to describe their pain. METHODS: Sixty-one children participated, mean age 11 y, suffering from acute pain (n=25) and pain associated with juvenile idiopathic arthritis (JIA, n=36). Children rated their pain intensity on the POM-VAS (visual analogue scale, 0-10 cm). Thereafter, children were asked whether each sensory and affective word on the POM-WDS was known to them, and whether each word described their pain experience. RESULTS: Seventeen out of 23 words were known to at least 70% of the sample. The least recognized word was grinding. Children age 6-16 knew fewer words than the adolescents. Age was a significant determinant for whether the children knew the words grinding (odds ratio (OR) 20.08, p<0.01), gnawing (OR 5.92, p < 0.05), unbearable (OR 8.02, p<0.05), and excruciating (OR 20.17, p<0.001). Terrible (OR 33.3, p<0.05), aching (OR 44.5, p<0.05) and sore (OR 5.4, p<0.05) were selected more often by children with acute pain than with JIA. CONCLUSION: Further studies will be required to determine the suitability of using the POM-WDS with children.