Inflammatory Blood Signature Related to Common Psychological Comorbidity in Chronic Pain.

Chronic pain is characterized by high psychological comorbidity, and diagnoses are symptom-based due to a lack of clear pathophysiological factors and valid biomarkers. We investigate if inflammatory blood biomarker signatures are associated with pain intensity and psychological comorbidity in a mixed chronic pain population. Eighty-one patients (72% women) with chronic pain (>6 months) were included. Patient reported outcomes were collected, and blood was analyzed with the Proseek Multiplex Olink Inflammation Panel (Bioscience Uppsala, Uppsala, Sweden), resulting in 77 inflammatory markers included for multivariate data analysis. Three subgroups of chronic pain patients were identified using an unsupervised principal component analysis. No difference between the subgroups was seen in pain intensity, but differences were seen in mental health and inflammatory profiles. Ten inflammatory proteins were significantly associated with anxiety and depression (using the Generalized Anxiety Disorder 7-item scale (GAD-7) and the Patient Health Questionnaire (PHQ-9): STAMBP, SIRT2, AXIN1, CASP-8, ADA, IL-7, CD40, CXCL1, CXCL5, and CD244. No markers were related to pain intensity. Fifteen proteins could differentiate between patients with moderate/high (GAD-7/PHQ-9 > 10) or mild/no (GAD-7/PHQ-9 < 10) psychological comorbidity. This study further contributes to the increasing knowledge of the importance of inflammation in chronic pain conditions and indicates that specific inflammatory proteins may be related to psychological comorbidity.

Baseline Pro-Inflammatory Cytokine Levels Moderate Psychological Inflexibility in Behavioral Treatment for Chronic Pain.

Background: The medical and scientific communities struggle to understand chronic pain and find effective treatments. Multimodal approaches are encouraging but show significant individual differences. Methods: Seventy-eight persons (56 women) with chronic pain received Acceptance and Commitment Therapy and provided blood samples before and after treatment. The participants completed surveys with the blood sampling. Blood plasma was analyzed for IL-6 and TNF-α levels with the Olink Inflammation Panel (Olink Bioscience Uppsala, Sweden). The treatment effects and moderating effects of low-grade inflammation on changes in outcomes were analyzed using linear mixed models. Results: Pain interference (p < 0.001) and psychological inflexibility (p < 0.001) improved significantly during treatment, but pain intensity did not (p = 0.078). Cytokine levels did not change over the course of the treatment (IL-6/TNF-α p = 0.086/0.672). Mean baseline levels of IL-6 and TNF-α moderated improvement in psychological inflexibility during the course of treatment (p = 0.044), but cytokine levels did not moderate changes in pain interference (p = 0.205) or pain intensity (p = 0.536). Conclusions: Higher baseline inflammation levels were related to less improvement in psychological inflexibility. Low-grade inflammation may be one factor underlying the variability in behavioral treatment in chronic pain.

Evaluating the construct validity and internal consistency of the Sickness Questionnaire in a Swedish sample of adults with longstanding pain.

OBJECTIVES: Low-grade inflammation is a possible contributing factor in the development and persistence of chronic primary pain syndromes. Related to inflammatory activity is sickness behavior, a set of behavioral responses including increased pain sensitivity, fatigue, malaise, fever, loss of appetite, as well as depressive behavior and anhedonia. To capture these behavioral responses and their relation to longstanding pain, psychometrically sound self-report questionnaires are needed. The Sickness Questionnaire (SicknessQ) was developed to assess self-reported sickness behavior based on studies on acute immune activation while maintaining relevance for persistent conditions. The aim of the current study was to evaluate aspects of the validity and reliability of the SicknessQ in a Swedish sample of persons with longstanding pain. METHODS: Aspects of construct validity were evaluated by means of performing a confirmatory factor analysis (CFA) (testing structural validity) and by relevant hypothesis testing i.e., that ratings of sickness behavior in combination with other related factors (e.g., depression and anxiety) would be significantly related to ratings of avoidance. Reliability was evaluated by means of analyzing the internal consistency of items. RESULTS: Following the CFA, a non-significant Chi-Square test (χ2 [32, N=190] = 42.95, p=0.094) indicated perfect model fit. Also, the relative fit indices supported adequate model fit (CFI = 0.978; TLI = 0.969; RMSEA = 0.0430). Sickness behavior (p<0.0001), depression (p<0.05) and pain duration (p<0.05) significantly contributed to the regression model, explaining 45% of the total variance in avoidance. Internal consistency was adequate, as indicated by a Cronbach's α value of 0.82 for the entire questionnaire. CONCLUSIONS: Results indicate that the SicknessQ has adequate structural validity as well as adequate internal consistency, and is significantly associated with avoidance. The SicknessQ appears to have utility as a self-report questionnaire to assess symptoms of sickness behavior for adults with longstanding pain.

An observational study on risk factors for prolonged opioid prescription after severe trauma.

BACKGROUND AND AIMS: Trauma is one of the most common causes of morbidity and mortality in people of working age. Following surgery, approximately 10% of patients develop persistent postsurgical pain. Chronic pain is a complex phenomenon that can adversely affect quality of life and is associated with psychiatric conditions such as anxiety and depression. Pharmacological treatment is normally insufficient to fully alleviate chronic pain and improve functional capacity, especially in the long term. The appropriateness of opioid treatment in chronic non-cancer pain has become increasingly examined with high numbers of serious side effects including drug dependency and death. The present study was based on clinical observations suggesting that a problematic opioid use can be initiated during trauma care, which implies the importance of evaluating opioid therapy and its effect on trauma patients. Specific attention is given to patients with known psychiatric conditions which may render them more vulnerable to develop problematic opioid use. The aim of this observational study was to broadly characterize patients referred to a pain specialist after severe trauma regarding their trauma type, psychiatric co-morbidity, and opioid prescription pattern. This was done to tentatively investigate possible risk factors for long-term opioid use following trauma. METHODS: Trauma patients referred to the Pain Center at Karolinska University Hospital, Sweden (n=29) were recruited for the study over a period of 2 years. Demographic information, trauma-related data as well as psychiatric diagnoses and pharmacological prescriptions were retrieved from the registry SweTrau and electronic medical records. RESULTS: Among the 29 participants (age range 21-55 years, median=34; 76% male), 14 (48%) were prescribed opioids at least once during the 6-months period preceding the trauma. For 21 patients (72%) opioids were prescribed 6 months after the trauma. One year after the trauma, 18 patients (62%) still had prescriptions for opioids corresponding to daily use or more, and two other patients used opioids intermittently. Twenty patients (69%) had psychiatric diagnoses before the trauma. According to the medical records, 17 patients (59%) received pharmacological treatment for psychiatric conditions in the six months period preceding the trauma. During the follow-up period, psychiatric pharmacological treatment was prescribed for 27 (93%) of the patients. CONCLUSION AND IMPLICATIONS: For most of the participants opioids were still being prescribed one year after trauma. The majority presented with psychiatric co-morbidity before trauma and were also prescribed psychiatric medication. Findings support the notion that patients with a complex pain situation in the acute phase following trauma are at risk for prolonged opioid prescription. These results, although tentative, point at psychiatric co-morbidity, opioid use before trauma, high injury severity, extensive surgery and extended hospital stay as risk factors for prolonged opioid prescription after severe trauma. This study is purely observational, with a small sample and non-controlled design. However, these data further emphasize the need to identify patients at risk for developing problematic long-term opioid use following trauma and to ensure appropriate pain treatment.

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.