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Correlations between pain phenotypes and psychiatric traits such as depression and the personality trait of neuroticism are not fully understood. In this study, we estimated the genetic correlations of eight pain phenotypes (defined by the UK Biobank, n = 151,922-226,683) with depressive symptoms, major depressive disorders and neuroticism using the the cross-trait linkage disequilibrium score regression (LDSC) method integrated in the LD Hub. We also used the LDSC software to calculate the genetic correlations among pain phenotypes. All pain phenotypes, except hip pain and knee pain, had significant and positive genetic correlations with depressive symptoms, major depressive disorders and neuroticism. All pain phenotypes were heritable, with pain all over the body showing the highest heritability (h 2  = 0.31, standard error = 0.072). Many pain phenotypes had positive and significant genetic correlations with each other indicating shared genetic mechanisms. Our results suggest that pain, neuroticism and depression share partially overlapping genetic risk factors.

Knee pain is one of the most common musculoskeletal complaints that brings people to medical attention. Approximately 50% of individuals over the age of 50 report an experience of knee pain within the past 12 months. We sought to identify the genetic variants associated with knee pain in 171,516 subjects from the UK Biobank cohort and seek supporting evidence in cohorts from 23andMe, the Osteoarthritis Initiative, and the Johnston County Osteoarthritis Project. We identified two loci that reached genome-wide significance in the UK Biobank: rs143384, located in GDF5 ( P  = 1.32 × 10 -12 ), a gene previously implicated in osteoarthritis; and rs2808772, located near COL27A1 ( P  = 1.49 × 10 -8 ). These findings were supported in cohorts with self-reported osteoarthritis/radiographic knee osteoarthritis without pain information. In this report on genome-wide association of knee pain, we identified two loci in or near GDF5 and COL27A1 that are associated with knee pain., Competing Interests: Competing interestsJ.S., A.A. and members of the 23andMe Research Team are employees of 23andMe, Inc., and hold stock or stock options in 23andMe. Other authors declare no competing interests.

A previous study has reported that chronic pain is associated with a higher incidence of overall and site-specific cancer in subsequent years. The aim of this study was to confirm or refute these findings. In 1996, a cohort of 6940 individuals was recruited, and information on chronic pain, general health and socio-demographic details collected. Ten years later, a record linkage study was conducted between these data and the routinely collected national dataset for cancer registration. Hazard ratios for the incidence of all cancers and eight cancer-specific sites by chronic pain status were calculated. Eighty-four percent of individuals from the original cohort were linked. After excluding those with a known previous cancer diagnosis, all non-melanoma skin cancers and cancers which were not first occurrences, a total of 646 cancers had occurred in 607 people since the baseline study. The overall cancer incidence in the cohort was 10.4% over the 10 years. There were no significant associations between chronic pain and all cancer, or any of the eight cancer-specific sites, after adjustment for age and sex. There was a significant increased risk of developing lymphoma/leukaemia amongst those with all chronic pain and various causes of chronic pain on univariate analysis. After adjustment, these trends remained, although most of the associations were no longer significant. There were no significant differences between those with severe chronic pain compared to those with mild chronic pain. The findings suggest that those with chronic pain are not at a significantly increased risk of developing cancer., (Copyright 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.)

Previous research has clearly demonstrated a link between chronic pain and poor health, and has suggested a link with increased mortality, though the latter is less consistent. In 1996 a cohort of 6940 individuals was recruited, and information collected, about reported chronic pain status, general health and socio-demographic details. Ten years later, a record linkage was conducted between these data and the routinely collected national dataset for death registration. Primary cause of death was classified according to ICD-10 codes. Survival analysis was conducted to obtain unadjusted and multi-adjusted hazard ratios (HR) for all-cause, system-specific and disease-specific mortality by chronic pain status. A total of 5858 (84.4%) of individuals from the original cohort were linked, including 1557 (26.6%) who had died. Survival analysis found significant associations between any reported chronic pain and all-cause mortality (HR 1.32, 99% CI, 1.14-1.54) and a number of specific causes. However, when we adjusted for socio-demographic factors and reported long-term limiting illness, the significant association was lost. Survival among those reporting severe chronic pain was significantly worse than among those reporting mild or no chronic pain. After adjustment for socio-demographic factors and reported long-term limiting illness, severe chronic pain remained significantly associated with all-cause mortality (HR 1.49, 99% CI 1.21-1.84) and all circulatory system disease deaths (HR 1.68, 99% CI 1.20-2.35). The evident association between any chronic pain and increased mortality can apparently be explained by confounding caused by socio-demographic factors. However, severe chronic pain is associated with increased risk of mortality, independent of socio-demographic factors., (Copyright (c) 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.)

More than 1 in 10 adults in the general population experience chronic widespread body pain (CWP), which lies at one end of a continuous spectrum of pain ranging in both severity and duration. Neuroendocrine factors can modify the effect of known psychological and psychosocial risk factors for progression along the spectrum of pain and development of CWP, and genetic variants that affect neuroendocrine and neural processing potentially affect susceptibility to chronic pain development. We have examined variants across genes encoding the beta2-adrenergic receptor (ADRB2) and catecholamine-O-methyltransferase (COMT) - key neuroendocrine signalling factors - in a large population-based sample to determine whether these may be involved in pain progression and CWP development. A nested association study was conducted using individuals from the 1958 British Birth Cohort Study who had been assessed for pain status. Genotypes were available for nine single nucleotide polymorphisms (SNPs) across ADRB2 and 11 SNPs across COMT. ADRB2 SNPs rs12654778 and rs1042713 were associated either with CWP alone (p=0.02 for both) or with position along pain spectrum (pain status; p=0.04). Common functional ADRB2 haplotype combinations were also associated with pain status (p(model)=0.002) and, further, with both extent and duration of pain (p(model)=0.003 and p(model)=0.002, respectively). There were no associations of either CWP or pain status with COMT genotypes or haplotypes. These results are the first to suggest that functional ADRB2 variants are involved in regulating pain status at a population level. A role for COMT in chronic pain development was not identified, though could not be excluded., (Copyright 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Chronic pain is generally regarded as being divided into two mutually exclusive pain mechanisms: nociceptive and neuropathic. Recently, this dichotomous approach has been questioned and a model of chronic pain being 'more or less neuropathic' has been suggested. To test whether such a spectrum exists, we examined responses by patients with chronic pain to validated neuropathic pain assessment tools and compared these with ratings of certainty about the neuropathic origin of pain by their specialist pain physicians. We examined 200 patients (100 each with nociceptive and neuropathic pain) and administered the self-complete Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS score) and the Neuropathic Pain Scale (NPS). Clinicians were asked to rate their certainty of the presence of neuropathic pain mechanisms on a 100 mm visual analogue scale (VAS) (0='not at all neuropathic in origin' to 100='completely neuropathic in origin'). The whole sample was divided into tertiles based on ascending ratings of diagnostic certainty by clinicians using the VAS and labelled 'unlikely', 'possible' and 'definite' neuropathic pain. There were significant differences in median S-LANSS and NPS composite scores between all tertile groups. There were also significant differences between many S-LANSS and NPS item scores between groups. We have shown that higher scores on both the S-LANSS and the NPS are indicative of greater clinician certainty of neuropathic pain mechanisms being present. These data support the theoretical construct that pain can be more or less neuropathic and that pain of predominantly neuropathic origin may be a useful clinical concept.

Unlabelled: Progress in the understanding of chronic pain with neuropathic features has been hindered by a lack of epidemiologic research in the general population. The Leeds Assessment of Neuropathic Symptoms and Signs score (S-LANSS) was recently validated for use in postal surveys, making the identification of pain of predominantly neuropathic origin possible. Six family practices in 3 UK cities (Aberdeen, Leeds, and London) generated a total random sample of 6,000 adults. The mailed questionnaire included demographic items, chronic pain identification, and intensity questions, the S-LANSS, the Level of Expressed Needs questionnaire, and the Neuropathic Pain Scale. With a corrected response rate of 52%, the prevalence of any chronic pain was 48% and the prevalence of pain of predominantly neuropathic origin was 8%. Respondents with this chronic neuropathic pain were significantly more likely to be female, slightly older, no longer married, living in council rented accommodation, unable to work, have no educational qualifications, and be smokers than all other respondents. Multiple logistic regression modeling found that pain of predominantly neuropathic origin was independently associated with older age, gender, employment (being unable to work), and lower educational attainment. Respondents with this pain type also reported significantly greater pain intensity, higher scores on the NPS, higher levels of expressed need, and longer duration of pain. This is the first estimate of the prevalence and distribution of pain of predominantly neuropathic origin in the general population, using a previously validated and reliable data collection instrument., Perspective: Chronic pain with neuropathic features appears to be more common in the general population than previously suggested. This type of pain is more severe than other chronic pain but distributed similarly throughout sociodemographic groups.

Relatively little is known about the clinical importance of symptoms not presented to healthcare services. Using data from a community survey we examined the health status among those with chronic pain who reported using or not using healthcare services. Individuals with chronic pain who had used healthcare services in the previous year had poorer health than symptomatic responders who had not used services, irrespective of the severity of chronic pain. The findings suggest that there is little point in trying to detect and treat individuals not currently presenting to healthcare services with their pain.

Background: and Objectives. There is a case for considering chronic pain as a distinct diagnosis in primary care, independent of its cause or body site, to allow development of common management strategies. This study examined the prevalence and factors associated with chronic pain among women still in the Royal College of General Practitioners' Oral Contraception Study, and compared the factors associated with chronic pain arising at different body sites, to examine the support for this case., Methods: A survey of 11797 women examined the presence and site(s) of chronic pain, and other health factors. Socio-demographic factors, attendance at the family doctor for the pain and self-rated health were examined for their association with any chronic pain and site-specific chronic pain., Results: Thirty-eight percent of women reported any chronic pain, for which most had attended their family doctor. Manual social class, former oral contraceptive use and area of residence were independently associated with any chronic pain. Chronic pain at different sites was associated with different socio-demographic factors, and different proportions of women consulting their family doctor or reporting unfavourable health. These proportions rose with the number of reported sites of chronic pain., Conclusions: The findings confirm the high prevalence of chronic pain and its importance to primary care. They suggest that chronic pain occurrence at different body sites varies across population subgroups, with differences in its impact on health. These differences call into question the independence of a chronic pain diagnosis. However, other factors common to any chronic pain support the development of common management and prevention strategies in primary care, and the variations highlighted will inform the targeting of these. The number of sites of chronic pain may be more important than the actual site(s) in determining its impact.

Recent research suggested associations between pain and subsequent all-cause and cancer-specific mortality. This study examined death and cancer development within six years of reporting pain, among women in the Royal College of General Practitioners Oral Contraception Study. We found no associations between 'any' or 'chronic' pain and subsequent all-cause mortality or cancer. We found a higher risk of death from respiratory disease among women reporting pain (adjusted odds ratio [AOR] = 2.5), a higher mortality among women reporting chronic chest pain (AOR = 1.75), and a higher risk of subsequent cancer among women reporting head or abdomen pain. Given the high prevalence of pain symptoms, these findings may be important, and warrant further research.

Little is known about the course of chronic pain in the community. Such information is needed for the prevention and management of chronic pain. We undertook a 4-year follow-up study of 2184 individuals living in Grampian, UK to describe patterns and predictors of change in chronic pain over time. In October 2000, participants completed a postal questionnaire including case definition questions, the chronic pain grade questionnaire, the SF-36 and socio-demographic questions. Information from this questionnaire was compared to information collected from a similar questionnaire in 1996. A response rate of 83% was achieved for the follow-up study. The overall prevalence of chronic pain (pain or discomfort present either all the time or on and off for 3 months or longer) increased from 45.5% at baseline to 53.8% at follow-up. Seventy-nine percent of those with chronic pain at baseline still had it at follow-up. The average annual incidence was 8.3% and the average annual recovery rate was 5.4%. Individuals in the study samples who are in lowest quartile of SF-36 domains--physical functioning, social functioning and bodily pain at baseline--were more likely to develop chronic pain at follow-up, and respondents who were retired were less likely to develop chronic pain. Individuals in the study samples in the lowest quartile of SF-36 domains, bodily pain and general health at baseline, were less likely to recover from their chronic pain, as were those aged 45-74 compared with those aged 25-34. We concluded that chronic pain is a common, persistent problem in the community with relatively high incidence and low recovery rates. The lack of association between onset or recovery from chronic pain and most traditional socio-demographic factors, highlights the need to broaden the range of factors included in studies of chronic pain aetiology., (Copyright 2002 International Association for the Study of Pain)

Background: There is no standard method of measuring change in chronic pain severity. Clinical trials commonly use serial assessment scales, completed at two points in time, to estimate change in pain severity, while clinicians usually ask patients to make a retrospective assessment of change. How the two methods compare is not known., Aim: To assess different methods of measuring change in chronic pain severity, by comparing changes in scores on a serial measure of chronic pain severity using the Chronic Pain Grade (CPG) questionnaire and responders' retrospective perception of change in pain severity., Design of Study: Postal self-completion questionnaires., Setting: The Grampian region of Scotland., Method: Postal questionnaires were sent in March and September 1998 to a random sample of 535 adults with chronic pain, drawn from responders to a postal survey of the region conducted in 1996., Results: Corrected response rates of 87.5% and 90.7% were obtained. Over a six-month period poor levels of agreement were found, with responders' retrospective perceptions mirroring recorded changes in 41.8% of individuals (kappa = 0.081). A low partial correlation coefficient between the two measures (-0.209) was also found. Over a two-year period there were again poor levels of agreement, with responders' retrospective perceptions mirronng recorded changes in 35.2% of individuals (kappa = 0.071). A low partial correlation coefficient (-0.401) was again found., Conclusion: There was poor agreement and low correlation between two commonly used methods for assessing change in pain severity over time. This finding has important implications for both service practitioners and researchers.

Background: Chronic pain is known to be very common in the community. Less is known about the epidemiology of more significant or severe chronic pain. The impact of chronic pain in the community, in terms of general health, employment and interference with daily activity, has not been quantified., Objectives: The aim of this study was to describe the prevalence and distribution in the community of chronic pain defined as 'significant' and 'severe', and to explore the impact of chronic pain on health and activity., Methods: A questionnaire survey was carried out of a sample drawn from the general population in the Grampian region of SCOTLAND: Questionnaires were sent to a random sample of 4611 individuals aged 25 years and over, stratified for age and gender, selected from the practice lists of 29 general practices (total practice population 136,383). The study instrument included a case definition questionnaire, from which were identified individuals with 'any chronic pain' (pain of at least 3 months duration). The instrument also included a level of expressed need questionnaire and the chronic pain grade questionnaire, from which were derived definitions for 'significant chronic pain' (based on the reported need for treatment and professional advice) and 'severe chronic pain' (based on reported intensity and pain-related disability). The SF-36 general health questionnaire and demographic questions were also included., Results: Of the sample, 14.1% reported 'significant chronic pain', and this was more prevalent among women and older age groups. A total of 6.3% reported 'severe chronic pain', and this was more common in older age groups. On multiple logistic regression modelling, female gender, housing tenure, employment category and educational attainment were found to be independently associated with both 'significant' and 'severe' chronic pain. The presence of 'any', 'significant' and 'severe' chronic pain had progressively more marked adverse associations with employment, interference with daily activities and all measured dimensions of general health., Conclusions: Comparison of the epidemiology of 'significant chronic pain' and 'severe chronic pain' with 'any chronic pain' allows an understanding of the more clinically important end of the chronic pain spectrum. These results support the suggestion that chronic pain is multidimensional, both in its aetiology and in its effects, particularly at this end of the spectrum. This must be addressed in management and in further research.

Chronic pain is a common and disabling condition, with a high impact on health and the health services in the community. The extent of help-seeking behaviour and factors that influence this are complex, but poorly understood. A simple, valid measure of help-seeking behaviour would be useful for community-based research, with a view to developing and evaluating interventions. The aims of the study were to test a hierarchical scale designed to measure help-seeking behaviour in chronic pain in postal surveys of the community, and to explore factors associated with responses. As part of a community survey of chronic pain, we developed the Level of Expressed Need (LEN) scale, based on questions about the use of treatment and professional advice for chronic pain. We compared this scale with two measures of chronic pain severity--the Chronic Pain Grade (CPG), and the Glasgow Pain Questionnaire (GPQ)--and analyzed associations with the SF36 general health questionnaire and demographic variables. Of 3605 respondents (corrected response rate 82%), 1817 reported chronic pain. Of these, 17% were at the mildest and 28% at the severest LEN. There were strong correlations with both the CPG (r=0.48) and the GPQ (r=0.55). There were, however, many important disparities in responses to these measures. Several other factors were independently associated with a high LEN in chronic pain: female gender, lower educational level, and physical, mental, pain and general health dimensions of the SF36 questionnaire. The LEN is a useful tool for measuring the help-seeking response to chronic pain in the general population. The findings confirm that this response is influenced by clinical and demographic factors in addition to the severity of the pain. Further development work will strengthen the instrument to explore these., (Copyright 2001 European Federation of Chapters of the International Association for the Study of Pain.)

Our understanding of the natural history of chronic pain in the community is limited. This is partly due to the lack of a validated measure of chronic pain severity known to be responsive to change over time. The Chronic Pain Grade questionnaire has been shown to be valid and reliable for use in a general population as a self-completion questionnaire. However, its reliability and validity for use in longitudinal studies and its responsiveness to change over time has not yet been assessed. We undertook a postal survey designed to test the responsiveness and the validity of the Chronic Pain Grade questionnaire over time. A random sample of 560 chronic pain patients, aged 25 years and over was drawn from an existing cohort and stratified for age, gender and chronic pain severity. Subjects were re-surveyed by a postal self-completion questionnaire consisting of the Chronic Pain Grade and the SF-36 general health questionnaire, which is known to be responsive to change in health over time. To test whether changes in CPG scores correlated with changes in SF-36 scores, Spearman's rank correlation coefficients were calculated. A response rate of 86% was achieved for the follow-up study. The majority of SF-36 scores changed in the hypothesized directions. Changes in CPG scores were significantly correlated with changes in most of the SF-36 domains. We concluded that the CPG is a useful and valid objective instrument for measuring change in severity of chronic pain over time and could be used in longitudinal studies of chronic pain severity.

Background: Chronic pain is recognised as an important problem in the community but our understanding of the epidemiology of chronic pain remains limited. We undertook a study designed to quantify and describe the prevalence and distribution of chronic pain in the community., Methods: A random sample of 5036 patients, aged 25 and over, was drawn from 29 general practices in the Grampian region of the UK and surveyed by a postal self-completion questionnaire. The questionnaire included case-screening questions, a question on the cause of the pain, the chronic pain grade questionnaire, the level of expressed needs questionnaire, and sociodemographic questions., Findings: 3605 questionnaires were returned completed. 1817 (50.4%) of patients self reported chronic pain, equivalent to 46.5% of the general population. 576 reported back pain and 570 reported arthritis; these were the most common complaints and accounted for a third of all complaints. Backward stepwise logistic-regression modelling identified age, sex, housing tenure, and employment status as significant predictors of the presence of chronic pain in the community. 703 (48.7%) individuals with chronic pain had the least severe grade of pain, and 228 (15.8%) the most severe grade. Of those who reported chronic pain, 312 (17.2%) reported no expressed need, and 509 (28.0%) reported the highest expressed need., Interpretation: Chronic pain is a major problem in the community and certain groups within the population are more likely to have chronic pain. A detailed understanding of the epidemiology of chronic pain is essential for efficient management of chronic pain in primary care.

Chronic pain is a very common cause of suffering, disability and economic adversity in the community. It is a complex problem that needs to be understood in a multi-dimensional way for effective management. Most research to date has been based in specialist clinics rather than in primary care, with consequently limited findings. Chronic pain differs from acute pain in that management follows a rehabilitative rather than a treatment model, though these are not mutually exclusive. Full assessment of the patient, preferably multi-disciplinary, will improve his or her outlook. Management should be holistic, rigorous in the application of conventional therapies (including analgesics and physical therapy) and ready to admit an improved understanding of psychological and social techniques. There may be a role for complementary therapies. As a large proportion of chronic pain presents only in the community, there may be a role for greater primary care input to management.

Chronic pain is an important cause of suffering, disability and loss of productivity within the community. Chronic pain can also be viewed as a multidimensional phenomenon, and may be associated with increased suffering of a social and psychological nature, as well as physical suffering. In this paper, the severity of the chronic pain gradings (CPG) is defined in terms of physical, social and psychological well-being, as measured by the SF36 and Glasgow Pain Questionnaire. Although previous work has shown the chronic pain grade to be a valid measure of chronic pain severity, little is known of the relationship between this and other health measures. A random sample of 5036 individuals, representative of the general population, stratified for age and sex, was drawn. A further sample of 4175 patients was drawn from a list of patients enrolled for repeat prescriptions for analgesic medication. A questionnaire survey was carried out, and response rates of 82 and 87% were achieved, respectively. The comparisons described confirm the widespread impact of chronic pain on all aspects of health, supporting the multidimensional view. These findings are important in addressing the management of chronic pain patients, and in particular, the social and psychological well-being of a patient needs to be addressed in parallel with the physical well-being in order to successfully reduce the suffering associated with chronic pain.

The Chronic Pain Grade questionnaire has been proposed as an interview-administered, multi-dimensional measure of chronic pain severity in selected populations with chronic pain in the United States of America. It has not previously been tested in the United Kingdom, in self-completion form or in an unselected general population. We undertook a postal survey to assess its reliability, validity and acceptability in these circumstances, using a general practice population in Scotland, with a practice population of 11202 patients. A random sample of 400 patients aged over 18 was drawn, stratified for age, gender and receipt or non-receipt of regular prescriptions for pain-relieving medication. The dimensions and sub-scales of the Chronic Pain Grade were compared with the SF-36 general health questionnaire and questions relating to duration of any pain and attempts to seek treatment for this. The methodological approach proposed by Streiner and Norman (1989) was used to assess validity and reliability. A response rate of 76% was achieved. Cronbach's alpha was > 0.9 and item-total correlations were all high, indicating good internal consistency and reliability. Validity was confirmed by psychometric testing, including confirmatory factor analysis. Good correlations with comparable dimensions of the SF-36 general health questionnaire confirmed convergent validity. Construct validity was confirmed by testing scores against duration of pain and treatment sought for pain. We concluded that the Chronic Pain Grade questionnaire is a useful, reliable and valid measure of severity of chronic pain. It translates well into UK English and is acceptable in general population postal research.