Chronic pain epidemiology and its clinical relevance

SummaryChronic pain affects ∼20% of the European population and is commoner in women, older people, and with relative deprivation. Its management in the community remains generally unsatisfactory, partly because of lack of evidence for effective interventions. Epidemiological study of chronic pain, through an understanding of its distribution and determinants, can inform the development, targeting, and evaluation of interventions in the general population. This paper reviews current knowledge of risk markers associated with chronic pain and considers how these might inform management and prevention. Risk factors include socio-demographic, clinical, psychological, and biological factors. These are relevant to our understanding of chronic pain mechanisms and the nature of, and responses to, current and future treatments. Chronic pain affects ∼20% of the European population and is commoner in women, older people, and with relative deprivation. Its management in the community remains generally unsatisfactory, partly because of lack of evidence for effective interventions. Epidemiological study of chronic pain, through an understanding of its distribution and determinants, can inform the development, targeting, and evaluation of interventions in the general population. This paper reviews current knowledge of risk markers associated with chronic pain and considers how these might inform management and prevention. Risk factors include socio-demographic, clinical, psychological, and biological factors. These are relevant to our understanding of chronic pain mechanisms and the nature of, and responses to, current and future treatments. Editor's key points•Identifying risk factors allows development of healthcare strategies to reduce the burden of chronic pain.•Around 20% of the population may be affected, with a huge impact on the wider society.•Some risk factors cannot be changed (e.g. gender, age); others can be modified (e.g. pain severity, mood).•Further epidemiological studies are an essential part of a chronic pain research strategy. •Identifying risk factors allows development of healthcare strategies to reduce the burden of chronic pain.•Around 20% of the population may be affected, with a huge impact on the wider society.•Some risk factors cannot be changed (e.g. gender, age); others can be modified (e.g. pain severity, mood).•Further epidemiological studies are an essential part of a chronic pain research strategy. Epidemiology is the 'study of the distribution and determinants of health-related states or events in specified populations and the applications of this study to control health problems'.1Last R A Dictionary of Epidemiology. 4th Edn. International Epidemiological Association, Oxford2001Google Scholar Good epidemiological research on chronic pain provides important information on prevalence and factors associated with its onset and persistence. Improving our understanding of associated factors will inform our clinical management, limiting severity, and minimizing disability. There is a strong argument that the most recent estimations of global burden of disease have underestimated the contribution of chronic pain.2Croft P Blyth FM Van der Windt D The global occurrence of chronic pain: an introduction.in: Croft P Blyth FM Van der Windt D Chronic Pain Epidemiology'From Aetiology to Public Health. Oxford University Press, New York2010: 9-18Crossref Scopus (5) Google Scholar By 2030, the WHO predicts that the four leading contributors of global burden of disease will be unipolar depression, coronary heart disease, cerebrovascular disease, and road traffic accidents.3Mathers C Fat WHOThe global burden of disease: 2004 update. D. 2008http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/Crossref Scopus (39) Google Scholar Chronic pain is an important co-morbidity associated with all of these. But chronic pain is more than just a co-morbidity of other identifiable disease or injury. Chronic pain is now acknowledged as a condition in its own right, underpinned by an agreed set of definitions and taxonomy.4IASPClassification of chronic pain. Descriptions of chronic pain syndromes and definitions of pain terms.Pain Suppl. 1986; 3: S1-226PubMed Google Scholar 5Tracey I Bushnell M How neuroimaging studies have challenged us to rethink: is chronic pain a disease?.J Pain. 2009; 10: 1113-1120Abstract Full Text Full Text PDF PubMed Scopus (319) Google Scholar Approximately 20% of the adult European population have chronic pain6Breivik H Collett B Ventafridda V Cohen R Gallacher D Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment.Eur J Pain. 2006; 10: 287-333Crossref PubMed Scopus (3540) Google Scholar and, in addition to the physical and emotional burden it brings, the financial cost to society is huge, currently estimated at more than €200 billion per annum in Europe and $150 billion per annum in the USA.5Tracey I Bushnell M How neuroimaging studies have challenged us to rethink: is chronic pain a disease?.J Pain. 2009; 10: 1113-1120Abstract Full Text Full Text PDF PubMed Scopus (319) Google Scholar Fewer than 2% of sufferers ever attend a pain clinic6Breivik H Collett B Ventafridda V Cohen R Gallacher D Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment.Eur J Pain. 2006; 10: 287-333Crossref PubMed Scopus (3540) Google Scholar with the remainder managed mainly in primary care, if anywhere.7Smith B Torrance N Management of chronic pain in primary care.Curr Opin Support Palliat Care. 2011; 5: 137-142Crossref PubMed Scopus (40) Google Scholar While important recent advances in understanding pain mechanisms bring the possibility of new treatments, management of chronic pain is nonetheless generally unsatisfactory; two-thirds of sufferers report dissatisfaction with current treatment and most chronic pain persists for many years.8Elliott A Smith B Hannaford P Smith W Chambers W The course of chronic pain in the community: results of a 4-year follow-up study.Pain. 2002; 99: 299-307Abstract Full Text Full Text PDF PubMed Scopus (270) Google Scholar We need to understand the reasons for this, with a view to improving treatment. In addition to research on the pathophysiology of pain mechanisms, it is important to understand the risk factors associated with the presence and development of chronic pain, as this will allow the design and targeting of preventive and management strategies. Risk factors include socio-demographic, clinical, psychological, and biological factors, and recent research has elucidated many of these, with potential clinical relevance. One important aspect is the translation of research on risk factors from animal or small human samples to the general population.9Mao J Current challenges in translational pain research.Trends Pharmacol Sci. 2012; 33: 568-573Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar This paper will review our current understanding of risk markers associated with chronic pain, considering how this might be applied to the prevention and management of chronic pain. The socio-demographic factors associated with chronic pain are well described across different pain conditions10Smith B Macfarlane G Torrance N Epidemiology of chronic pain, from the laboratory to the bus stop: time to add understanding of biological mechanisms to the study of risk factors in population-based research.Pain. 2007; 127: 5-10Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar (Box 1).Box 1Socio-demographic factors associated with chronic pain•Female gender•Older age•Lower socio-economic status•Geographical and cultural background•Employment status and occupational factors•History of abuse or interpersonal violence •Female gender•Older age•Lower socio-economic status•Geographical and cultural background•Employment status and occupational factors•History of abuse or interpersonal violence In addition to a female preponderance for chronic pain, women consistently report lower pain thresholds, lower pain tolerance, and greater unpleasantness (or intensity) with pain with different analgesic sensitivity.11Wiesenfeld-Hallin Z Sex differences in pain perception.Gend Med. 2005; 2: 137-145Abstract Full Text PDF PubMed Scopus (431) Google Scholar There is some evidence for a biological basis for apparent sex differences in pain experiences involving oestrogens.12Craft R Modulation of pain by estrogens.Pain. 2007; 132: S3-12Abstract Full Text Full Text PDF PubMed Scopus (268) Google Scholar However, the greatest gender differences are seen in the prevalence of chronic pain syndromes.13Greenspan J Craft R LeResche L Studying sex and gender differences in pain and analgesia. A consensus report.Pain. 2007; 132: S26-S45Abstract Full Text Full Text PDF PubMed Scopus (717) Google Scholar Recent evidence suggests that the occurrence of disabling chronic pain continues to rise with old age. Although the onset of pain per se does not have a clear relationship with age,14Dionne C Dunn K Croft P Does back pain prevalence really decrease with increasing age? 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Population-based studies of chronic pain have consistently shown that chronic pain occurrence is inversely related to socio-economic status17Blyth FM Chronic pain'is it a public health problem?.Pain. 2008; 137: 465-466Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar 18Poleshuck E Green C Socioeconomic disadvantage and pain.Pain. 2008; 136: 235-238Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar with evidence that people living in adverse socioeconomic circumstances experience more chronic pain and greater pain severity,19Brekke M Hjortdahl P Kvien T Severity of musculoskeletal pain: relationship to socioeconomic inequality.Soc Sci Med. 2002; 54: 221-228Crossref PubMed Scopus (118) Google Scholar 20Eachus J Chan P Pearson N Propper C Davey-Smith G An additional dimension to health inequality: disease severity and socioeconomic position.J Epidemiol Community Health. 1999; 53: 603-611Crossref PubMed Scopus (84) Google Scholar independent of other demographic, and clinical factors. There is also evidence of both geographical and cultural variation in occurrence of chronic pain.6Breivik H Collett B Ventafridda V Cohen R Gallacher D Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment.Eur J Pain. 2006; 10: 287-333Crossref PubMed Scopus (3540) Google Scholar The occurrence of pain, or the extent to which pain interferes with life, can be influenced by demands, expectations, control and fear of re-injury at work, specific occupational factors, employer and co-worker reactions to pain, or even by broader issues such as the job market.21Shaw W Linton S Pransky G Reducing sickness absence from work due to low back pain: how well do intervention strategies match modifiable risk factors?.J Occup Rehabil. 2006; 16: 591-605Crossref PubMed Scopus (88) Google Scholar There is a growing body of literature from large-scale national surveys that pain is more common among people who report a history of abuse and violence at any age, in both domestic and public settings.22Ellsberg M Jansen H Heise L et al.Intimate partner violence and women's physical and mental health in the WHO multi-country study on women's health and domestic violence: an observational study.Lancet. 2008; 371: 1165-1172Abstract Full Text Full Text PDF PubMed Scopus (1258) Google Scholar 23Sachs-Ericsson N Kendall-Tackett K Hernandez A Childhood abuse, chronic pain, and depression in the National Comorbidity Survey.Child Abuse Negl. 2007; 31: 531-547Crossref PubMed Scopus (149) Google Scholar This effect appears to be additional to the risk caused by physical injuries and pain, and highlights the need to elicit any history of domestic, sexual, or criminal violence in assessing the propensity to chronic pain and in managing its impact. A prospective population-based study in the North of England (EpifunD study) concluded that there was a strong relationship between lack of sunshine, lower temperatures, and pain reporting, postulating climate as a possible risk factor.24Macfarlane TV Mcbeth J Jones GT Nicholl B Macfarlane GJ Whether the weather influences pain? Results from the EpiFunD study in North West England.Rheumatology. 2010; 49: 1513-1520Crossref PubMed Scopus (20) Google Scholar However, this relationship may be, at least in part, mediated through lifestyle factors associated with cooler and duller days (less exercise, poorer sleep, and higher reported boredom). Similarly, a seasonal effect suggests the potential role of vitamin D, low levels of which in some (but not all) studies have been shown to be related to the report of pain.25Straube S Andrew Moore R Derry S McQuay HJ Vitamin D and chronic pain.Pain. 2009; 141: 10-13Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar Although many of these risk factors are un-modifiable or not amenable to medical intervention, it is important to recognize them, as they inform a targeted approach to chronic pain assessment and management. Dedicated coding and inclusion within routinely collected data sources and disease registries will enable routine population and health system surveillance of chronic pain. This will also aid visibility, linking chronic pain to existing (better-funded) health priority areas such as cancer, injury, obesity, and healthy ageing.26Blyth F van der Windt D Croft P Introduction to chronic pain as a public health problem.in: Croft P Blyth FM van der Windt D Chronic Pain Epidemiology - From Aetiology to Public Health. Oxford University Press, New York2010: 279-287Crossref Scopus (1) Google Scholar The existence of both individual-level risk factors and population-level risk factors for the onset or persistence of pain suggests that opportunities for intervention exist at more than one level.17Blyth FM Chronic pain'is it a public health problem?.Pain. 2008; 137: 465-466Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar Ignoring population-level factors and intervening exclusively on high-risk individuals (such as in specialist pain clinics) could limit options for reducing the overall community burden of chronic pain. Perhaps the most important clinical factor for chronic pain at a specific site is pain (acute pain, or chronic pain at a different site). The more severe the pain and the greater number of pain sites, the more likely severe chronic pain.8Elliott A Smith B Hannaford P Smith W Chambers W The course of chronic pain in the community: results of a 4-year follow-up study.Pain. 2002; 99: 299-307Abstract Full Text Full Text PDF PubMed Scopus (270) Google Scholar 27Bergman S Herrstrom P Jacobsson L Petersson I Chronic widespread pain: a three year follow-up of pain distribution and risk factors.J Rheumatol. 2002; 29: 818-825PubMed Google Scholar 28Elliott A Hannaford P Chambers W Smith W Factors related to the onset and persistence of chronic back pain in the community: results from a general population follow-up study.Spine. 2004; 29: 1032-1040Crossref PubMed Scopus (143) Google Scholar This highlights the importance of pain management, not just in the relief of suffering, but also as a preventive activity. As Bingel and colleagues29Bingel I Tracey I Wiech K Neuroimaging as a tool to investigate how cognitive factors influence analgesic drug outcomes.Neurosci Lett. 2012; 520: 149-155Crossref PubMed Scopus (18) Google Scholar highlighted, neuroimaging of pain has evolved from providing evidence that pain is processed in the brain at all to a sophisticated, mechanism-orientated research tool that can address a plethora of specific aspects related to the processing, perception, and modulation of pain. Functional brain imaging has provided objective proof of pain perception both in experimentally-induced and in disease-related pain.30Gracely R Geisser M Giesecke T et al.Pain catastrophizing and neural responses to pain among persons with fibromyalgia.Brain. 2004; 127: 835-843Crossref PubMed Scopus (666) Google Scholar 31Mayer E Berman S Suyenobu B et al.Differences in brain responses to visceral pain between patients with irritable bowel syndrome and ulcerative colitis.Pain. 2005; 115: 398-409Abstract Full Text Full Text PDF PubMed Scopus (249) Google Scholar From this, we now know that chronic pain patients display an altered brain activation in response to acute pain stimuli.32Apkarian A Bushnell M Treede R Zubieta J Human brain mechanisms of pain perception and regulation in health and disease.Eur J Pain. 2005; 9: 463-484Crossref PubMed Scopus (2237) Google Scholar There is also some evidence to suggest that brain changes associated with chronic pain may be reversible after effective treatment.33Rodriguez-Raecke R Niemeier A Ihle K Brain gray matter decrease in chronic pain is the consequence and not the cause of pain.J Neurosci. 2009; 29: 13746-13750Crossref PubMed Scopus (381) Google Scholar 34Gwilym S Fillipini N Douaud G Thalamic atrophy associated with painful osteoarthritis of the hip is reversible after arthroplasty; a longitudinal voxel-based-morphometric study.Arthritis Rheum. 2010; 62: 2930-2940Crossref PubMed Scopus (234) Google Scholar In healthy individuals, neuroimaging studies have found that grey matter plasticity can be induced by repetitive experimental noxious stimuli as early as 8 days (after daily pain stimulus for 8 consecutive days), and that this receded between 22 days and 12 months later.35Teutsch S Herken W Bingel U Changes in brain gray matter due to repetitive painful stimulation.Neuroimage. 2008; 42: 845-849Crossref PubMed Scopus (156) Google Scholar That these anatomical changes within the brain occur in the early stages of pain (before pain is labelled as chronic) further suggests that early intervention will be important in preventing chronicity, though this remains to be tested clinically. It is uncertain whether there is pre-existing brain vulnerability to chronic pain, or whether these changes arise as a result of chronic pain. Even if brain responses are found to be tracking pain, these could conceivably represent co-located non-nociceptive functions.36Davis K Neuroimaging of pain: what does it tell us?.Curr Opin Support and Palliat Care. 2011; 5: 116-121Crossref PubMed Scopus (39) Google Scholar 37Davis K Racine E Collett B Neuroethical issues related to the use of brain imaging: can we and should we use brain imaging as a biomarker to diagnose chronic pain?.Pain. 2012; 153: 1555-1559Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar Mindful of these caveats, future neuroimaging has the potential to optimize treatment or even offer personalized therapy, improve pain diagnostics in those who cannot communicate this and indicate targets for drug development.37Davis K Racine E Collett B Neuroethical issues related to the use of brain imaging: can we and should we use brain imaging as a biomarker to diagnose chronic pain?.Pain. 2012; 153: 1555-1559Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar Anxiety, depression, and catastrophizing beliefs about pain are associated with chronic pain and with a poor prognosis in people with various pain conditions.38Boersma K Linton S Expectancy, fear and pain in the prediction of chronic pain and disability: a prospective analysis.Eur J Pain. 2006; 10: 551-557Crossref PubMed Scopus (139) Google Scholar, 39van der Windt D Croft P Penninx B Neck and upper limb pain: more pain is associated with psychological distress and consultation rate in primary care.J Rheumatol. 2002; 29: 564-569PubMed Google Scholar, 40van der Windt D Kuijpers T Jellema P van der Heijden G Bouter L Do psychological factors predict outcome in both low-back pain and shoulder pain?.Ann Rheum Dis. 2007; 66: 313-319Crossref PubMed Scopus (86) Google Scholar, 41Nijrolder I van der Windt D van der Horst H Prediction of outcome in patients presenting with fatigue in primary care.Br J Gen Pract. 2009; 59: e101-e109Crossref PubMed Scopus (10) Google Scholar The temporal relationship between chronic pain and mental health remains unclear and is likely bi-directional. There is evidence that top-down (central and cognitive) influences on pain perception may be greater than peripheral input, as exemplified by the analgesic effect of placebo.42Price D Finniss D Benedetti F A comprehensive review of the placebo effect: recent advances and current thought.Annu Rev Psychol. 2008; 59: 565-590Crossref PubMed Scopus (804) Google Scholar It is postulated that placebo analgesia can be potentiated by increasing endogenous opioid tone (e.g. after exercise) and, conversely, that anxiety reduces this endogenous effect. 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Clinically, the implication is that we need to address chronic pain as an important health component of multi-morbidity and chronic stress, and that doing so successfully might result in a corresponding improvement in overall health. Recent evidence has also shown that those with severe chronic pain have increased risk of all-cause mortality, independent of socio-demographic factors.50Torrance N Elliott A Lee A Smith B Severe chronic pain is associated with increased 10 year mortality. A cohort record linkage study.Eur J Pain. 2010; 14: 380-386Crossref PubMed Scopus (189) Google Scholar In particular, those reporting severe chronic pain were more than twice as likely to have died 10 years later from ischaemic heart disease or respiratory disease than those reporting no or mild chronic pain.50Torrance N Elliott A Lee A Smith B Severe chronic pain is associated with increased 10 year mortality. 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In general, attitudes and beliefs about established pain are important predictors in identifying those who are likely to develop long-term and disabling pain.54Rainville J Smeets R Bendix T Tveito T Poiraudeau S Indahl A Fear-avoidance beliefs and pain avoidance in low back pain–translating research into clinical practice.Spine J. 2011; 9: 895-903Abstract Full Text Full Text PDF Scopus (128) Google Scholar 55Darlow B Fullen B Dean S Hurley D Baxter G Dowell A The association between health care professional attitudes and beliefs and the attitudes and beliefs, clinical management, and outcomes of patients with low back pain: a systematic review.Eur J Pain. 2012; 16: 3-17Crossref PubMed Scopus (277) Google Scholar A recent review concluded that women tend to cope better with pain when they use pain-attentional focus or re-interpreting pain sensation strategies, whereas distraction techniques may be more efficient among men.56Racine M Tousignant-Laflamme Y Kloda L Dion D Dupuis G Choinière M A systematic literature review of 10 years of research on sex/gender and pain perception'Part 2: do biopsychosocial factors alter pain sensitivity differently in women and men?.Pain. 2012; 153: 619-663Abstract Full Text Full Text PDF PubMed Scopus (287) Google Scholar Passive coping strategies (e.g. taking medication, resting, hot-cold packs) were associated with three times as many healthcare visits and doubling the level of pain-related disability.57Blyth F March L Nicholas M Cousins M Self-management of chronic pain: a population-based study.Pain. 2005; 113: 285-292Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar compared with the use of active strategies (e.g. exercise). 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