there is some evidence for the role of estrogens and genetics, including sex-specific differences in the contribution of pain- related genes (Wang et al., 2020). Employment status People who are not in employment because of ill health or disability are more likely to have chronic pain than those who are employed. Occupational risk factors for chronic pain include poor job control, expectations of a return to work (including fear around a recurring injury), lack of work autonomy or the ability to modify work, job satisfaction, and higher perceived level of difficulty of job requirements. Chronic neck and shoulder pain was found to be an independent predictor of chronic pain and related to work stress. Non-manual workers were less likely to report chronic pain than people who hold manual occupations (Suur-Uski et al., 2022). A similar study also demonstrated that chronic pain relates to working status: Chronic pain was present in 78.9% of those who were unemployed, but only in 39.8% of those in paid employment and 42.4% of those in voluntary or unpaid work. This relationship, however, may be bidirectional in that people with chronic pain may be less likely to be at work because of their pain (Sheikhzadeh et al., 2021). The extent of the burden on healthcare from chronic pain has also been related to the education level and socioeconomic level of patients. A score to assess work disability from pain leading to absent days demonstrated that, in both genders, more locations of pain, smoking, less education, and obesity were related to a higher risk of time off work as a result of pain. Ethnicity and cultural background Evidence comparing the incidence and prevalence of pain from different regions of the world suggests that there are substantial and complex ethnic variations in the prevalence and outcomes of pain-related conditions, although the mechanisms behind these remain poorly understood. A report demonstrated how Caucasian patients have been found to experience less pain and less pain-related disability than Black patients. In another survey of 500, 000 people in the UK, those who self-identified as white were less likely to report chronic pain than those reporting Black, Asian, or mixed ethnicity. However, once adjusted for income employment, and adverse life events, the association between self-reported ethnicity and chronic pain was significantly attenuated. The prevalence of chronic pain and its associated disability is greater in developing countries than in developed countries (Verma & Tiwari, 2022). Socioeconomic background Population studies reliably show that the prevalence of chronic pain is inversely related to socioeconomic factors. Those who are socioeconomically deprived are not only more likely to experience chronic pain than people from more affluent areas, but they are also more likely to experience more severe pain and a greater level of pain-related disability. People who have low levels of education, perceived income inequalities, and high levels of neighborhood deprivation are more likely to experience chronic pain than those who have higher levels of education, less perceived income inequality, and who live in more affluent neighborhoods. The economic impact of chronic pain compounds the cycle of pain’s complex interrelationship with socioeconomic deprivation. Although an individual’s socioeconomic and educational background are nonmodifiable, it is clear that political attention to these factors can have a profound influence on the future prevalence and severity of chronic pain at a societal level (Hobson et al., 2022). Physical activity The evidence on the relationship between the incidence and prevalence of pain and physical activity appears to be slightly controversial. A few systematic reviews conclude that exercise and physical activity have positive effects on chronic pain, with improved quality of life and physical function, reduced pain severity, and few adverse effects, although the quality of evidence is variable. Compliance with exercise interventions is key to their success; interventions with measured high
compliance yielded a significantly larger reduction in pain than those with uncertain or unmonitored compliance (Marques et al., 2022). The specific effects of physical activity on chronic pain are hard to determine because of the heterogeneity of chronic pain and exercise regimes, and study limitations, including limited follow-up periods and small sample sizes. However, there is evidence of benefit for some types of physical activity in particular chronic pain conditions: Aquatic exercise can improve chronic back pain and improve physical function, supervised aerobic and strength training has been shown to reduce pain in patients with fibromyalgia, and tai chi had a beneficial effect in reducing arthritis pain. Yoga has also been shown to have a beneficial impact on those with chronic pain. Recommendations for including physical activity in treatment plans for the management of chronic pain have started to feature in national and international care guidelines. Multimorbidity and mortality Perhaps it is no surprise that patients with co-morbid physical and mental chronic diseases are more liable to suffer chronic pain than those without. Up to 88% of those with chronic pain reportedly have additional chronic diagnoses. Even after adjusting for known socioeconomic and environmental confounders (e.g., age, gender, smoking, deprivation, and education), there is an increased co-occurrence of chronic pain with depression and cardiovascular disease (Athnaiel et al., 2022). Approximately a third of patients with chronic pulmonary disease and coronary heart disease report experiencing chronic pain. The presence of co-morbidities also complicates the clinical management of people with chronic pain by limiting the applicability of disease-specific clinical guidelines and reducing the treatment options available for optimal pain control. In people with other medical co-morbidities, chronic pain is an independent risk factor for all-cause mortality. Patients diagnosed with severe chronic pain are twice as likely to have died 10 years later from ischemic heart disease or respiratory disease than those who report mild chronic pain or were pain-free. Those who were ‘resilient to pain’—people who experienced a high pain intensity but documented a low pain disability—had an improved 10-year survival rate compared with people who were not resilient to pain (You et al., 2022). Genetics Judging from available evidence, the relationship between chronic pain and genes can be aptly described as complex. Genes act at many levels of the biological arrangement to shape the experience of chronic pain, influencing emotional, behavioral, and biological processes. Sensitivity to painful stimuli and pain tolerance are partly genetically determined. Chronic pain is a heritable phenotype and the presence of chronic pain clusters in family groups through genetic and ‘maternal’ effects. It also may be a result of important genetic contributions to underlying diseases, which will include chronic pain (Axon & Chien, 2021). One of the current challenges in chronic pain epidemiology is to determine which genes contribute to chronic pain and what their roles are. Currently, at least 150 genes have been reported to be associated with chronic pain in humans, and this number is ever-expanding. Among others, they include genes from immune, inflammatory, and stress-related pathways, including COMT and OPRM . Specific genetic variants have been identified with rare chronic pain conditions, such as SNC9A with erythromelalgia. A recent systematic review of genetic factors associated with chronic neuropathic pain found that variants in HLA genes, COMT, OPRM1, TNFA, IL6 , and GCH1 , were identified in more than one study (Veluchamy et al., 2021). Weight Obesity, defined as a BMI of greater than 30, is related to multimorbidity and is an independent predictor of chronic pain. Obesity increases chronic pain in several ways, including placing strain on weight-bearing joints, reducing physical activity, and contributing to overall body deconditioning. One study suggests that nearly 40% of people who are obese experience chronic
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