Managing chronic widespread pain in primary care : a qualitative study of patient perspectives and implications for treatment delivery

Funding The MUSICIAN trial was supported by an award from Arthritis Research UK, Chesterfield, UK. Grant number: 17292. The funding body approved the design of the study. They played no role in the collection, analysis, and interpretation of data or the writing of the manuscript.Peer reviewedPublisher PD

Chronic pain and mortality : a systematic review

Background: Chronic pain is common, often widespread and has a substantial impact on health and quality of life. The relationship between chronic pain and mortality is unclear. This systematic review aimed to identify and evaluate evidence for a relationship between chronic pain and mortality. Methods: A search of ten electronic databases including EMBASE and MEDLINE was conducted in March 2012, and updated until March 2014. Observational studies investigating the association between chronic or widespread pain (including fibromyalgia) and mortality were included. Risk of bias was assessed and a meta-analysis was undertaken to quantify heterogeneity and pool results. A narrative review was undertaken to explore similarities and differences between the included studies. Results: Ten studies were included in the review. Three reported significant associations between chronic or widespread pain and mortality in unadjusted results. In adjusted analyses, four studies reported a significant association. The remaining studies reported no statistically significant association. A meta-analysis showed statistically significant heterogeneity of results from studies using comparable outcome measures (n = 7)(I2 = 78.8%) and a modest but non-significant pooled estimate (MRR1.14,95%CI 0.95–1.37) for the relationship between chronic pain and all-cause mortality. This association was stronger when analysis was restricted to studies of widespread pain (n = 5,I2 = 82.3%) MRR1.22(95%CI 0.93–1.60). The same pattern was observed with deaths from cancer and cardiovascular diseases. Heterogeneity is likely to be due to differences in study populations, follow-up time, pain phenotype, methods of analysis and use of confounding factors. Conclusion: This review showed a mildly increased risk of death in people with chronic pain, particularly from cancer. However, the small number of studies and methodological differences prevented clear conclusions from being drawn. Consistently applied definitions of chronic pain and further investigation of the role of health, lifestyle, social and psychological factors in future studies will improve understanding of the relationship between chronic pain and mortality

Allostatic load and pain severity in older adults:Results from the English Longitudinal Study of Ageing

Pain is common in older adults, is frequently experienced as stressful, and is associated with increased morbidity and mortality. Stress regulatory systems are adaptive to challenge and change, allostasis, until demands exceed the adaptive capacity contributing to dysregulation, resulting in a high allostatic load. A high allostatic load is associated with increased risk of morbidity and mortality. Pain severity, based on the average intensity of frequent pain, was hypothesized to be positively associated with AL. Four formulations of AL were investigated. Cross-sectional data from Wave 4 (2008-2009) of the English Longitudinal Study of Aging (ELSA) were analyzed. Covariates in the model included age, sex, education, smoking status, alcohol consumption, activity level, depression and common comorbid health conditions. A total of 5341 individuals were included; mean age 65.3(±9.2) years, 55% female, 62.4% infrequent or no pain, 12.6% mild pain, 19.1% moderate pain, and 5.9% severe pain. Severe pain was associated with greater AL defined by all four formulations. The amount of variance explained by pain severity and the covariates was highest when allostatic load was defined by the high risk quartile (12.9%) and by the clinical value (11.7%). Findings indicate a positive relationship between pain severity and AL. Further investigation is needed to determine if there is a specific AL signature for pain that differs from other health conditions

BayesGmed : An R-package for Bayesian Causal Mediation Analysis

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Modelling and classifying joint trajectories of self-reported mood and pain in a large cohort study

It is well-known that mood and pain interact with each other, however individual-level variability in this relationship has been less well quantified than overall associations between low mood and pain. Here, we leverage the possibilities presented by mobile health data, in particular the "Cloudy with a Chance of Pain" study, which collected longitudinal data from the residents of the UK with chronic pain conditions. Participants used an App to record self-reported measures of factors including mood, pain and sleep quality. The richness of these data allows us to perform model-based clustering of the data as a mixture of Markov processes. Through this analysis we discover four endotypes with distinct patterns of co-evolution of mood and pain over time. The differences between endotypes are sufficiently large to play a role in clinical hypothesis generation for personalised treatments of comorbid pain and low mood

The relationship between back pain and mortality in older adults varies with disability and gender: results from the Cambridge City over-75s Cohort (CC75C) study.

BACKGROUND: This study aims to determine whether older adults reporting back pain (BP) are at increased risk of premature mortality, specifically, to examine the association with disabling/non-disabling pain separately. METHODS: Participants aged ≥75 years were recruited to the Cambridge City over-75s Cohort (CC75C) study. Participants answered interviewer-administered questions on BP and were followed up until death. The relationship between BP and mortality was examined using Cox regression, adjusted for potential confounding factors. Separate models were computed for men and women. RESULTS: From 1174 individuals with BP data, the date of death was known for 1158 (99%). A significant association was found between disabling BP and mortality (hazard ratio: 1.4; 95% confidence interval: 1.1-1.8) and this remained, albeit of borderline significance, following adjustment for socio-demographic variables and potential disease markers (1.3; 0.99-1.7). Further, this association was found to vary with sex: women experienced a 40% increase in the risk of mortality associated with disabling BP (1.4; 1.1-1.9), whereas no such increase was observed for men (1.0; 0.5-1.9). Participants with non-disabling BP were not at increased risk of mortality. CONCLUSIONS: This study confirmed previous findings regarding the relationship between pain and excess mortality. Further, we have shown that, among older adults, this association is specific to disabling pain and to women. Clinicians should be aware not only of the short-term implications of disabling BP but also the longer-term effects. Future research should attempt to understand the mechanisms underpinning this relationship to avoid excess mortality and should aim to determine why the relationship differs in men and women

Genetic variation in the hypothalamic–pituitary–adrenal stress axis influences susceptibility to musculoskeletal pain: results from the EPIFUND study

<b>Objectives</b> To determine if genetic variation in genes in the hypothalamic–pituitary–adrenal (HPA) axis, the primary stress response system, influences susceptibility to developing musculoskeletal pain.<p></p> <b>Methods</b> Pain and comorbidity data was collected at three time points in a prospective population-based cohort study. Pairwise tagging single nucleotide polymorphisms (SNPs) were selected and genotyped for seven genes. Genetic association analysis was carried out using zero-inflated negative binomial regression to test for association between SNPs and the maximum number of pain sites across the three time points in participants reporting pain, reported as proportional changes with 95% CIs. SNPs were also tested for association with chronic widespread pain (CWP) using logistic regression reporting odds ratios and 95% CI.<p></p> <b>Results</b> A total of 75 SNPs were successfully genotyped in 994 participants including 164 cases with persistent CWP and 172 pain-free controls. Multiple SNPs in SERPINA6 were associated with the maximum number of pain sites; for example, each copy of the T allele of rs941601 was associated with having 16% (proportional change=1.16, 95% CI 1.04 to 1.28, p=0.006) more pain sites compared to participants with the CC genotype. SERPINA6 gene SNPs were also associated with CWP. Significant associations between the maximum number of pain sites and SNPs in the CRHBP and POMC genes were also observed and a SNP in MC2R was also associated with CWP. Associations between SNPs and comorbidity of poor sleep quality and depression explained some of the associations observed.<p></p> <b>Conclusions</b> Genetic variation in HPA axis genes was associated with musculoskeletal pain; however, some of the associations were explained by comorbidities. Replication of these findings is required in independent cohorts

Do genetic predictors of pain sensitivity associate with persistent widespread pain?

Genetic risk factors for pain sensitivity may also play a role in susceptibility to chronic pain disorders, in which subjects have low pain thresholds. The aim of this study was to determine if proposed functional single nucleotide polymorphisms (SNPs) in the GTP cyclohydrolase (GCH1) and μ opioid receptor (OPRM1) genes previously associated with pain sensitivity affect susceptibility to chronic widespread pain (CWP). Pain data was collected using body manikins via questionnaire at three time-points over a four year period from subjects aged 25-65 in the North-West of England as part of a population based cohort study, EPIFUND. CWP was defined at each time point using standard criteria. Three SNPs forming a proposed "pain-protective" haplotype in GCH1 (rs10483639, rs3783641 and rs8007267) and two SNPs in OPRM1 (rs1777971 (A118G) and rs563649) were genotyped in cases with persistent CWP (CWP present at ≥2 time-points) and controls who were pain-free at all time-points. The expectation-maximisation algorithm was used to estimate haplotype frequencies. The frequency of the "pain-protective" (CAT - C allele of rs10483639, A allele of rs3783641 and T allele of rs8007267) haplotype was compared to the frequency of the other haplotypes between cases and controls using the χ2 test. Allele frequencies and carriage of the minor allele was compared between cases and controls using χ2 tests for the OPRM1 SNPs. The frequency of the proposed GCH1 "pain-protective" haplotype (CAT) did not significantly differ between cases and controls and no significant associations were observed between the OPRM1 SNPs and CWP. In conclusion, there was no evidence of association between proposed functional SNPs, previously reported to influence pain sensitivity, in GCH1 and OPRM1 with CWP. Further evidence of null association in large independent cohorts is required to truly exclude these SNPs as genetic risk factors for CWP

Hypothalamic-pituitary-adrenal stress axis function and the relationship with chronic widespread pain and its antecedents

In clinic studies, altered hypothalamic-pituitary-adrenal (HPA) axis function has been associated with fibromyalgia, a syndrome characterised by chronic widespread body pain. These results may be explained by the associated high rates of psychological distress and somatisation. We address the hypothesis that the latter, rather than the pain, might explain the HPA results. A population study ascertained pain and psychological status in subjects aged 25 to 65 years. Random samples were selected from the following three groups: satisfying criteria for chronic widespread pain; free of chronic widespread pain but with strong evidence of somatisation ('at risk'); and a reference group. HPA axis function was assessed from measuring early morning and evening salivary cortisol levels, and serum cortisol after physical (pain pressure threshold exam) and chemical (overnight 0.25 mg dexamethasone suppression test) stressors. The relationship between HPA function with pain and the various psychosocial scales assessed was modelled using appropriate regression analyses, adjusted for age and gender. In all 131 persons with chronic widespread pain (participation rate 74%), 267 'at risk' (58%) and 56 controls (70%) were studied. Those in the chronic widespread pain and 'at risk' groups were, respectively, 3.1 (95% CI (1.3, 7.3)) and 1.8 (0.8, 4.0) times more likely to have a saliva cortisol score in the lowest third. None of the psychosocial factors measured were, however, associated with saliva cortisol scores. Further, those in the chronic widespread pain (1.9 (0.8, 4.7)) and 'at risk' (1.6 (0.7, 3.6)) groups were also more likely to have the highest serum cortisol scores. High post-stress serum cortisol was related to high levels of psychological distress (p = 0.05, 95% CI (0.02, 0.08)). After adjusting for levels of psychological distress, the association between chronic widespread pain and post-stress cortisol scores remained, albeit slightly attenuated. This is the first population study to demonstrate that those with established, and those psychologically at risk of, chronic widespread pain demonstrate abnormalities of HPA axis function, which are more marked in the former group. Although some aspects of the altered function are related to the psychosocial factors measured, we conclude that the occurrence of HPA abnormality in persons with chronic widespread pain is not fully explained by the accompanying psychological stress

Testing the credibility, feasibility and acceptability of an optimised behavioural intervention (OBI) for avoidant chronic low back pain patients: protocol for a randomised feasibility study

Background: Chronic back pain continues to be a costly and prevalent condition. The latest NICE guidelines issued in 2009 state that for patients with persistent back pain (of between six weeks and twelve months duration), who are highly distressed and/or disabled and for whom exercise, manual therapy and acupuncture has not been beneficial, the evidence supports a combination of around 100 hours of combined physical and psychological treatment. This is costly, and may prove unacceptable to many patients. A key recommendation of these guidelines was for further randomised controlled trials (RCTs) of psychological treatment and to target treatment to specific sub-groups of patients. Recent trials that have included psychological interventions have shown only moderate improvement at best, and results are not maintained long term. There is therefore a need to test theoretically driven interventions that focus on specific high-risk sub-groups, in which the intervention is delivered at full integrity against a credible control. Methods/design: A feasibility study of a pragmatic randomised controlled trial comparing psychologist-delivered Contextual Cognitive Behavioural Therapy (CCBT) against Treatment As Usual (TAU) physiotherapy delivered by physiotherapists for the treatment of chronic lower back pain in ‘avoidant’ patients. Ninety-two patients referred for physiotherapy will be recruited and randomised on a 1:1 basis to receive CCBT or TAU. Treatment groups will be balanced by centre and pain interference score. Primary outcomes include assessing the credibility and acceptability of the intervention, and to demonstrate proof of principle through a greater change in pain acceptance in the CCBT arm, measured by the Acceptance and Action –II and the Chronic Pain Acceptance questionnaires. In addition, the feasibility of carrying out a full trial will be explored with reference to recruitment and follow-up rates including the assessment of the burden of outcome measure completion. Secondary patient outcomes include disability, pain, fear of movement, mood, quality of life, and global recovery. Outcomes are measured at three and six months post-randomisation. Discussion: This paper details the rationale, design, therapist training system and recruitment methods to be used in a feasibility study which will inform the design and efficient implementation of a future definitive RCT