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 pain, and that the pain they report is more likely to be moderate to severe than chronic pain in those who are not obese (Kerver et al., 2021). A large-scale population study found that the likelihood of reporting chronic pain increased proportionately with BMI: Compared with groups of people with a healthy BMI, in people with a BMI of 30–34, the rates of pain were 68%; the relative rates of chronic pain were 136% in those with a BMI of 35–39, and 254% in those with BMI >40. This increased prevalence of chronic pain is seen even after adjusting for the impact of obesity on other medical conditions, which contribute to multimorbidity and are independently associated with pain. There are both environmental and genetic elements to the relationship between pain and obesity. There is, however, limited evidence that weight loss improves chronic pain. However, there is evidence that being underweight is a consideration when managing patients with chronic pain: One study showed a higher chronic pain prevalence in men over 50 who had a BMI of less than 18.5; they also had higher rates of severe depression (Elma et al., 2022). Nutrition There is a connection between nutrition and the incidence of pain in a population, however, this relationship appears to be unclear. This, perhaps, stems from the large volume of papers and research submissions exploring this subject over the years. The conclusions from these submissions have suggested controversial links between these two. Nutrition management plans may be of benefit to patients with chronic pain by improving pain management and reducing cardiovascular risk factors that are related to chronic pain. There have been calls for patients with chronic pain to be offered personalized nutrition assessment and counseling targeted at improving diet and supplement use, and emerging evidence is that this may improve the quality of life and clinical outcomes in patients with chronic pain. Omega-3 as a diet supplement in preclinical trials did show an improvement in inflammatory pain, while garlic has been suggested to reduce pain severity in overweight women with knee arthritis (Vezza et al., 2021). A recent systematic review and meta-analysis of 23 papers found that interventions based on nutrition, particularly those testing an altered overall diet or a single nutrient, had
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