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Chronic Pain and Premature Aging – The Moderating Role of Physical Exercise
Abstract
Chronic pain induces a multitude of harmful effects; recently it has been suggested that chronic pain is also associated with premature aging, manifested in shortened telomere length (TL). However, evidence for this hypothesis is scarce and inconsistent. The aim was twofold: 1) Investigate whether chronic pain is associated with premature aging, and 2) Determine whether physical exercise (PE) moderates this association if it exists. Participants were 116 male subjects, with (n=67) and without chronic pain (n=49). Blood samples for TL analysis were collected and participants were interviewed and completed questionnaires. As a part of the cohort, we included people with physical disability; this variable was controlled in the analysis. The TL of individuals with chronic pain was significantly shorter than that of pain-free individuals. Regression analysis revealed a significant moderating effect of PE on chronic pain and TL, above and beyond the effects of disability, age, and weight. Whereas chronic pain was associated with shorter telomeres in participants who did not exercise, this association was non-significant among participants who did exercise. The results suggest that chronic pain is associated with premature ageing; however, PE may mitigate this association and may protect individuals against the harmful effects of chronic pain.
Perspective
The study suggest that it is important to monitor signs of premature ageing among chronic pain patients as they are at risk. However, chronic pain patients may benefit from regular physical exercise in this respect as it may moderate premature ageing.
... Time spent on earth (chronological aging) is a key risk factor for knee pain (Patel et al., 2013;Karttunen et al., 2015) and developing knee pain that severely limits daily activities (Dahlhamer et al., 2018a;Pitcher et al., 2019;Von Korff et al., 1992), may indirectly accelerate biological aging processes, which further impacts physical function (Badley et al., 1994) leading to morbidity and disability. There is evidence that those individuals with chronic pain and/or physical function decrements demonstrate premature aging (Lahav et al., 2021;Sibille et al., 2017;Stenholm et al., 2016). While both chronic pain and physical function limitations are heterogeneous with advancing age, other biological and environmental "aging" processes may influence this variation. ...
Knee pain is a leading cause of disability in the aging population and may indirectly accelerate biological aging processes. Chronological aging increases the risk of developing of knee pain and knee pain reduces physical function; however, limited data exist on how epigenetic aging, a known hallmark of biological aging shown to predict health span and mortality, may influence this relationship. The purpose of this study was to examine whether decreased physical performance associated with knee pain is mediated by markers of epigenetic aging. Participants (57.91 ± 8.04 years) with low impact knee pain (n = 95), high impact knee pain (n = 53) and pain-free controls (n = 26) completed self-reported pain, a blood draw and a short physical performance battery (SPPB) that included balance, walking, and sit to stand tasks. We employed an epigenetic clock previously associated with knee pain and shown to predict overall mortality risk (DNAmGrimAge). Bootstrapped-mediation analyses were used to determine associations of DNAmGrimAge and SPPB between pain groups. Those with high impact and low impact pain had a biologically older epigenetic age (5.14y ± 5.66 and 1.32y ± 5.41, respectively). However, while there were direct effects of pain on overall physical performance, these were not explained by epigenetic aging. Epigenetic aging only mediated the effect of pain on balance performance. Future work is needed to examine pain's impact on biological aging processes including epigenetic aging and its ultimate effect on physical function measures known to predict health span and mortality.
... Chronic pain is associated with increased risk of age-related health outcomes, including mortality [8][9][10]. Previous studies have shown that greater chronic pain severity is associated with elevated levels of pro-inflammatory cytokines, such as C-reactive protein (CRP) [2,[11][12][13] and shorter LTL [14][15][16][17]. The pathogenesis and progression of chronic pain appears to be influenced by a combination of physiological, psychosocial, and lifestyle factors [2,8,18]. ...
Elevated inflammatory cytokines and chronic pain are associated with shorter leukocyte telomere length (LTL), a measure of cellular aging. Micronutrients, such as 25-hydroxyvitamin D (vitamin D) and omega 3, have anti-inflammatory properties. Little is known regarding the relationships between vitamin D, omega 6:3 ratio, LTL, inflammation, and chronic pain. We investigate associations between vitamin D, omega 6:3 ratio, LTL, and C-reactive protein (CRP) in people living with/without chronic pain overall and stratified by chronic pain status. A cross-sectional analysis of 402 individuals (63% women, 79.5% with chronic pain) was completed. Demographic and health information was collected. Chronic pain was assessed as pain experienced for at least three months. LTL was measured in genomic DNA isolated from blood leukocytes, and micronutrients and CRP were measured in serum samples. Data were analyzed with general linear regression. Although an association between the continuous micronutrients and LTL was not observed, a positive association between omega 6:3 ratio and CRP was detected. In individuals with chronic pain, based on clinical categories, significant associations between vitamin D, omega 6:3 ratio, and CRP were observed. Findings highlight the complex relationships between anti-inflammatory micronutrients, inflammation, cellular aging, and chronic pain.
... Given that research has indicated that occupational status was linked with depression, that age and weight were associated with shorter TL (e.g., Mundstock et al., 2015), and, as found in our previous study on the same dataset (Lahav et al., 2021), that physical exercise was associated with longer TL, these factors served as a covariate in the present analysis. ...
Objectives:
Evidence suggests that individuals with physical disability may suffer from psychological distress and accelerated cellular aging, manifested by shortened telomere length (TL), compared with healthy individuals. Studies indicate that high levels of perceived stress and depression may increase the physiological susceptibility and thus, may contribute to a short TL. However, the moderating role of perceived stress and depression within the relationship between physical disability and TL remains unknown.
Methods:
The participants consisted of 119 male subjects (mean age 54.36 years, range 35-70). Of them, 30 were able-bodied and 86 had a physical disability: 34 were due to Poliomyelitis (polio) and 55 were due to spinal cord injury (SCI). Blood samples for TL analysis were collected; the participants completed questionnaires and underwent disability evaluation.
Results:
Participants with disability had a shorter TL as well as elevated levels of perceived stress and depression compared with able-bodied controls. Both the perceived stress and depression were correlated with a shorter TL. Nonetheless, perceived stress, rather than depression, moderated the relationship between disability and TL; among participants with higher perceived stress levels, in particular, individuals with physical disability had a shorter TL than the able-bodied controls.
Discussion:
The present findings suggest that individuals with physical disability and who exhibit high levels of perceived stress may be particularly vulnerable for accelerated cellular aging, suggesting that perceived stress can be used as a valuable target for intervention.
Chronic pain is a disease of long-lasting pain with unpleasant feelings mediated by central and (or) peripheral sensitization, its duration usually lasts more than 3 months or longer than the expected recovery time. The patients with chronic pain are manifested with enhanced sensitivity to noxious and non-noxious stimuli. Due to an incomplete understanding of the mechanisms, patients are commonly insensitive to the treatment of first line analgesic medicine in clinic. Thus, the exploration of non-opioid-dependent analgesia are needed. Recent studies have shown that “sinomenine,” the main active ingredient in the natural plant “sinomenium acutum (Thunb.) Rehd. Et Wils,” has a powerful inhibitory effect on chronic pain, but its underlying mechanism still needs to be further elucidated. A growing number of studies have shown that various immune cells such as T cells, B cells, macrophages, astrocytes and microglia, accompanied with the relative inflammatory factors and neuropeptides, are involved in the pathogenesis of chronic pain. Notably, the interaction of the immune system and sensory neurons is essential for the development of central and (or) peripheral sensitization, as well as the progression and maintenance of chronic pain. Based on the effects of sinomenine on immune cells and their subsets, this review mainly focused on describing the potential analgesic effects of sinomenine, with rationality of regulating the neuroimmune interaction.
Background
Physical activity may attenuate age-related cognitive decline by improving cerebrovascular function. The aim of this study was therefore to investigate effects of aerobic exercise training on cerebral blood flow (CBF), which is a sensitive physiological marker of cerebrovascular function, in sedentary older men.Methods
Seventeen apparently healthy men, aged 60–70 years and with a BMI between 25 and 35 kg/m2, were included in a randomized, controlled cross-over trial. Study participants were randomly allocated to a fully-supervised, progressive, aerobic exercise training or no-exercise control period for 8 weeks, separated by a 12-week wash-out period. Measurements at the end of each period included aerobic fitness evaluated using peak oxygen consumption during incremental exercise (VO2peak), CBF measured with pseudo-continuous arterial spin labeling magnetic resonance imaging, and post-load glucose responses determined using an oral glucose tolerance test (OGTT). Furthermore, cognitive performance was assessed in the domains of executive function, memory, and psychomotor speed.ResultsVO2peak significantly increased following aerobic exercise training compared to no-exercise control by 262 ± 236 mL (P < 0.001). CBF was increased by 27% bilaterally in the frontal lobe, particularly the subcallosal and anterior cingulate gyrus (cluster volume: 1008 mm3; P < 0.05), while CBF was reduced by 19% in the right medial temporal lobe, mainly temporal fusiform gyrus (cluster volume: 408 mm3; P < 0.05). Mean post-load glucose concentrations determined using an OGTT decreased by 0.33 ± 0.63 mmol/L (P = 0.049). Furthermore, executive function improved as the latency of response was reduced by 5% (P = 0.034), but no changes were observed in memory or psychomotor speed.Conclusion
Aerobic exercise training improves regional CBF in sedentary older men. These changes in CBF may underlie exercise-induced beneficial effects on executive function, which could be partly mediated by improvements in glucose metabolism. This clinical trial is registered on ClinicalTrials.gov as NCT03272061.
Background:
This study aims to assess the decline in telomere length (TL) with age and evaluate effect modification by gender, chronic stress, and comorbidity in a representative sample of the US population.
Methods:
Cross-sectional data on 7826 adults with a TL measurement, were included from the National Health and Nutrition Examination Survey, years 1999-2002. The population rate of decline in TL across 10-year age categories was estimated using crude and adjusted regression.
Results:
In an adjusted model, the population rate of decline in TL with age was consistent and linear for only three age categories: 20-29 (β = -0.0172, 95% CI: -0.0342, -0.0002), 50-59 (β = -0.0182, 95% CI: -0.0311, -0.0054) and 70-79 (β = -0.0170, 95% CI: -0.0329, -0.0011) years. The population rate of decline in TL with age was significantly greater for males and those with high allostatic load and a history of comorbidities. When the population rate of decline in TL was analyzed by gender in 10-year age bins, a fairly consistent yet statistically non-significant decline for males was observed; however, a trough in the rate was observed for females in the age categories 20-29 years (β = -0.0284, 95% CI: -0.0464, -0.0103) and 50-59 years (β = -0.0211, 95% CI: -0.0391, -0.0032). To further elucidate the gender difference observed in the primary analyses, secondary analyses were conducted with reproductive and hormonal status; a significant inverse association was found between TL and parity, menopause, and age at menopause.
Conclusions:
TL was shorter with increasing age and this decline was modified by gender, chronic stress and comorbidities; individuals with chronic morbidity and/or chronic stress and females in their twenties and fifties experienced greater decline. Female reproductive factors, i.e., parity and menopause, were associated with TL.
Objective:
To investigate the effect of different levels of exercise on telomere length.
Methods:
CINAHL, SPORTDiscus (EBSCO), OVID (Medline) and EMBASE databases were searched for eligible studies. Methodological quality was evaluated using the Newcastle-Ottawa Scale, and heterogeneity among the studies was assessed using the I-squared test. When heterogeneity among studies was high (I2 > 50%), a random-effects model was used (Review Manager version 5, Cochrane Collaboration, Copenhagen, Denmark); otherwise, a fixed-effects model was used.
Results:
Eleven eligible studies involving 15,645 participants were included in this meta-analysis. Longer telomere length was associated with physically active individuals, with a mean difference (MD) of 0.15; 95% confidence interval; 95% CI 0.05, 0.24; I2 = 99%. Longer telomere length was significantly associated with robust exercise (MD 0.08; 95% CI 0.04, 0.12); I2 = 99%, as was moderate exercise (MD 0.07; 95% CI 0.03, 0.11); I2 = 100%. Subgroup analysis revealed that longer telomere length was positively associated with exercise, regardless of sex, but was not statistically significant in elderly populations.
Conclusion:
Compared with inactive individuals, telomere lengths were longer in active subjects, regardless of the intensity of exercise.
Telomeres are nucleoprotein structures that cap the end of each chromosome arm and function to maintain genome stability. The length of telomeres is known to shorten with each cell division and it is well-established that telomere attrition is related to replicative capacity in vitro. Moreover, telomere loss is also correlated with the process of aging in vivo. In this review, we discuss the mechanisms that lead to telomere shortening and summarise telomere homeostasis in humans throughout a lifetime. In addition, we discuss the available evidence that shows that telomere shortening is related to human aging and the onset of age-related disease.
Purpose of review:
The aim of the present systematic review is to provide an up-to-date analysis of the research on the effects of exercise programs on heart rate variability (HRV) in individuals with type 2 diabetes mellitus (T2DM). An electronic search of the literature (PubMed, PEDro and Web of Science) was performed. "HRV", "heart rate variability", "exercise", "physical" and "diabetes" were the terms used for article retrieval. Lastly, 15 articles were selected. PRISMA methodology was employed and data were extracted according to the PICOS approach.
Recent findings:
Although HRV is not routinely measured in the management of T2DM, it is an important measure due to its relation with mortality and diabetic neuropathy. Physical exercise has become a therapy for T2DM, because it improves physical fitness and functional capacity, enhances metabolic control and insulin sensitivity, reduces inflammatory markers and neuropathy symptoms and can increase the regenerative capacity of cutaneous axons, slowing or preventing neuropathy progression. However, it is not clear to what extent physical exercise can improve HRV in this population. Participation in the 15 selected studies was similar in men and women (48.01% men and 51.99% women). All the intervention programs included aerobic training, and it was complemented by strength training in four studies. Duration of physical exercise sessions ranged between 30 and 75 min, the frequency being between 2 and 7 days/week. Statistically significant improvements in groups with diabetes, relative to baseline, were observed in nine studies. More than 3 days per week of aerobic training, complemented by strength training, during at least 3 months seems to improve HRV in T2DM. Weekly frequency might be the most important factor to improve HRV. These aspects could help to design better programs based in scientific evidence, incorporating HRV as an important variable associated with diabetic neuropathy and mortality.
Background. :
Chronic pain is prevalent, costly, and disabling among older adults. Although mobility decline is inevitable with aging, it is clear, from current evidence, that older adults with chronic pain experience a greater rate of functional mobility decline than their pain-free peers. Past studies suggest that pain expedites the age-related decline in functional mobility; however, the pathways through which pain affects mobility remain unclear. Gerontological experts hypothesize that the age-related decline in mobility may be driven by alterations in energy expenditure; these concepts are outlined in a model known as the Energetic Pathway of Mobility Loss. Pain may play a critical role in this process through a pathway of energetic inefficiency, physical inactivity, and decreased capacity.
Purpose.:
The purposes of this article are to 1) summarize the current literature that supports the Energetic Pathway of Mobility Loss model and 2) propose a new framework, known as the Pain Energy Model, to clarify how the disablement process may be amplified among older adults with painful conditions.
Conclusion.:
This new framework is designed to generate new clinical research and to suggest new clinical implications for older adults with painful conditions by identifying key steps and potential treatment targets in the pathway to functional mobility decline.
This is the protocol for a review and there is no abstract. The objectives are as follows:
To provide an overview of Cochrane systematic reviews in adults with chronic pain conditions to determine:
• the effectiveness of different physical activity and exercise interventions in the management of chronic pain in adults in reducing pain severity and its impact on function, quality of life, and health care use;
• the evidence for any adverse effects or harm associated with physical activity and exercise interventions that are intended to reduce chronic pain in adults.
Telomeres protect the integrity of information-carrying DNA by serving as caps on the terminal portions of chromosomes. Telomere length decreases with aging, and this contributes to cell senescence. Recent evidence supports that telomere length of leukocytes and skeletal muscle cells may be positively associated with healthy living and inversely correlated with the risk of several age-related diseases, including cancer, cardiovascular disease, obesity, diabetes, chronic pain, and stress. In observational studies, higher levels of physical activity or exercise are related to longer telomere lengths in various populations, and athletes tend to have longer telomere lengths than non-athletes. This relationship is particularly evident in older individuals, suggesting a role of physical activity in combating the typical age-induced decrements in telomere length. To date, a small number of exercise interventions have been executed to examine the potential influence of chronic exercise on telomere length, but these studies have not fully established such relationship. Several potential mechanisms through which physical activity or exercise could affect telomere length are discussed, including changes in telomerase activity, oxidative stress, inflammation, and decreased skeletal muscle satellite cell content. Future research is needed to mechanistically examine the effects of various modalities of exercise on telomere length in middle-aged and older adults, as well as in specific clinical populations.
Background:
Chronic pain is defined as pain lasting beyond normal tissue healing time, generally taken to be 12 weeks. It contributes to disability, anxiety, depression, sleep disturbances, poor quality of life, and healthcare costs. Chronic pain has a weighted mean prevalence in adults of 20%.For many years, the treatment choice for chronic pain included recommendations for rest and inactivity. However, exercise may have specific benefits in reducing the severity of chronic pain, as well as more general benefits associated with improved overall physical and mental health, and physical functioning.Physical activity and exercise programmes are increasingly being promoted and offered in various healthcare systems, and for a variety of chronic pain conditions. It is therefore important at this stage to establish the efficacy and safety of these programmes, and furthermore to address the critical factors that determine their success or failure.
Objectives:
To provide an overview of Cochrane Reviews of adults with chronic pain to determine (1) the effectiveness of different physical activity and exercise interventions in reducing pain severity and its impact on function, quality of life, and healthcare use; and (2) the evidence for any adverse effects or harm associated with physical activity and exercise interventions.
Methods:
We searched theCochrane Database of Systematic Reviews (CDSR) on the Cochrane Library (CDSR 2016, Issue 1) for systematic reviews of randomised controlled trials (RCTs), after which we tracked any included reviews for updates, and tracked protocols in case of full review publication until an arbitrary cut-off date of 21 March 2016 (CDSR 2016, Issue 3). We assessed the methodological quality of the reviews using the AMSTAR tool, and also planned to analyse data for each painful condition based on quality of the evidence.We extracted data for (1) self-reported pain severity, (2) physical function (objectively or subjectively measured), (3) psychological function, (4) quality of life, (5) adherence to the prescribed intervention, (6) healthcare use/attendance, (7) adverse events, and (8) death.Due to the limited data available, we were unable to directly compare and analyse interventions, and have instead reported the evidence qualitatively.
Main results:
We included 21 reviews with 381 included studies and 37,143 participants. Of these, 264 studies (19,642 participants) examined exercise versus no exercise/minimal intervention in adults with chronic pain and were used in the qualitative analysis.Pain conditions included rheumatoid arthritis, osteoarthritis, fibromyalgia, low back pain, intermittent claudication, dysmenorrhoea, mechanical neck disorder, spinal cord injury, postpolio syndrome, and patellofemoral pain. None of the reviews assessed 'chronic pain' or 'chronic widespread pain' as a general term or specific condition. Interventions included aerobic, strength, flexibility, range of motion, and core or balance training programmes, as well as yoga, Pilates, and tai chi.Reviews were well performed and reported (based on AMSTAR), and included studies had acceptable risk of bias (with inadequate reporting of attrition and reporting biases). However the quality of evidence was low due to participant numbers (most included studies had fewer than 50 participants in total), length of intervention and follow-up (rarely assessed beyond three to six months). We pooled the results from relevant reviews where appropriate, though results should be interpreted with caution due to the low quality evidence. Pain severity: several reviews noted favourable results from exercise: only three reviews that reported pain severity found no statistically significant changes in usual or mean pain from any intervention. However, results were inconsistent across interventions and follow-up, as exercise did not consistently bring about a change (positive or negative) in self-reported pain scores at any single point. Physical function: was the most commonly reported outcome measure. Physical function was significantly improved as a result of the intervention in 14 reviews, though even these statistically significant results had only small-to-moderate effect sizes (only one review reported large effect sizes). Psychological function and quality of life: had variable results: results were either favourable to exercise (generally small and moderate effect size, with two reviews reporting significant, large effect sizes for quality of life), or showed no difference between groups. There were no negative effects. Adherence to the prescribed intervention: could not be assessed in any review. However, risk of withdrawal/dropout was slightly higher in the exercising group (82.8/1000 participants versus 81/1000 participants), though the group difference was non-significant. Healthcare use/attendance: was not reported in any review. Adverse events, potential harm, and death: only 25% of included studies (across 18 reviews) actively reported adverse events. Based on the available evidence, most adverse events were increased soreness or muscle pain, which reportedly subsided after a few weeks of the intervention. Only one review reported death separately to other adverse events: the intervention was protective against death (based on the available evidence), though did not reach statistical significance.
Authors' conclusions:
The quality of the evidence examining physical activity and exercise for chronic pain is low. This is largely due to small sample sizes and potentially underpowered studies. A number of studies had adequately long interventions, but planned follow-up was limited to less than one year in all but six reviews.There were some favourable effects in reduction in pain severity and improved physical function, though these were mostly of small-to-moderate effect, and were not consistent across the reviews. There were variable effects for psychological function and quality of life.The available evidence suggests physical activity and exercise is an intervention with few adverse events that may improve pain severity and physical function, and consequent quality of life. However, further research is required and should focus on increasing participant numbers, including participants with a broader spectrum of pain severity, and lengthening both the intervention itself, and the follow-up period.
Purpose of review:
Converging evidence from animal models of stroke and clinical trials suggests that aerobic exercise has effects across multiple targets.
Recent findings:
The subacute phase is characterized by a period of heightened neuroplasticity when aerobic exercise has the potential to optimize recovery. In animals, low intensity aerobic exercise shrinks lesion size and reduces cell death and inflammation, beginning 24 h poststroke. Also in animals, aerobic exercise upregulates brain-derived neurotrophic factor near the lesion and improves learning. In terms of neuroplastic effects, clinical trial results are less convincing and have only examined effects in chronic stroke. Stroke patients demonstrate cardiorespiratory fitness levels below the threshold required to carry out daily activities. This may contribute to a 'neurorehabilitation ceiling' that limits capacity to practice at a high enough frequency and intensity to promote recovery. Aerobic exercise when delivered 2-5 days per week at moderate to high intensity beginning as early as 5 days poststroke improves cardiorespiratory fitness, dyslipidemia, and glucose tolerance.
Summary:
Based on the evidence discussed and applying principles of periodization commonly used to prepare athletes for competition, we have created a model of aerobic training in subacute stroke in which training is delivered in density blocks (duration × intensity) matched to recovery phases.
The combination of aerobic and resistance training (AER + RES) is recommended by almost every major organization to improve health-related risk factors associated with sedentary behavior. Since the release of the Physical Activity Guidelines for Americans in 2008, several large well-controlled trials and ancillary reports have been published that provide further insight into the effects of AER + RES on health-related outcomes. The current manuscript examines the literature on the effects of AER + RES on major clinical outcomes, including glucose homeostasis, cardiorespiratory fitness (CRF), and muscular strength, as well as other important clinical outcomes, including metabolic syndrome, hypertension, dyslipidemia, and quality of life. Collectively, research suggests that AER + RES and AER or RES alone improves glycemic control and insulin sensitivity compared with continued sedentary behavior. Significant changes in CRF are also observed, suggesting a reduction in cardiovascular disease-related mortality risk. Reduced adiposity, especially abdominal adiposity, and increased strength may also interact with CRF to promote additional health benefits associated with AER + RES. While findings from our review support current physical activity guidelines, a paucity of research limits the generalizability of the results.
The brain is the central organ involved in perceiving and adapting to social and physical stressors via multiple interacting mediators, from the cell surface to the cytoskeleton to epigenetic regulation and nongenomic mechanisms. A key result of stress is structural remodeling of neural architecture, which may be a sign of successful adaptation, whereas persistence of these changes when stress ends indicates failed resilience. Excitatory amino acids and glucocorticoids have key roles in these processes, along with a growing list of extra- and intracellular mediators that includes endocannabinoids and brain-derived neurotrophic factor (BDNF). The result is a continually changing pattern of gene expression mediated by epigenetic mechanisms involving histone modifications and CpG methylation and hydroxymethylation as well as by the activity of retrotransposons that may alter genomic stability. Elucidation of the underlying mechanisms of plasticity and vulnerability of the brain provides a basis for understanding the efficacy of interventions for anxiety and depressive disorders as well as age-related cognitive decline.
Regular physical activity in healthy individuals prevents development of chronic musculoskeletal pain; however, the mechanisms underlying this exercise-induced analgesia are not well understood. Interleukin-10(IL-10), an anti-inflammatory cytokine which can reduce nociceptor sensitization, increases during regular physical activity. Since macrophages play a major role in cytokine production and are present in muscle tissue, we propose that physical activity alters macrophage phenotype to increase IL-10 and prevent chronic pain. Physical activity was induced by allowing C57BL/6J mice free access to running wheels for 8 weeks and compared to sedentary mice with no running wheels. Using immunohistochemical staining of the gastrocnemius muscle to label regulatory (M2, secretes anti-inflammatory cytokines) and classical (M1, secretes proinflammatory cytokines) macrophages, the percentage of M2-macrophages increased significantly in physically active mice (68.5+4.6% of total) compared to sedentary mice (45.8+7.1% of total). Repeated acid injections into the muscle enhanced mechanical sensitivity of the muscle and paw in sedentary animals that does not occur in physically active mice; no sex differences occur in either sedentary or physically active mice. Blockade of IL-10 systemically or locally prevented the analgesia in physically active mice, i.e. mice developed hyperalgesia. Conversely, sedentary mice pretreated systemically or locally with IL-10 had reduced hyperalgesia after repeated acid injections. Thus, these results suggest that regular physical activity increases the percentage of regulatory macrophages in muscle and that IL-10 is an essential mediator in the analgesia produced by regular physical activity.
Introduction:
Fibromyalgia is a chronic disease of unknown etiology characterized by widespread muscle pain, with occupational, familial, social, physical and psychological performance involvement. The multidisciplinary approach to the disease leads to improvement in quality of life and symptomatology.
Objectives:
To evaluate the improvement of activities of daily living (ADL) and quality of life following a multidisciplinary intervention (Health Primary Care and Occupational Therapy).
Material and methods:
Pretest-posttest study performed with a simple random sample of 21 patients with fibromyalgia (range 16-55 years). The measurement was performed with the Barthel scale (ADL), the scale of Lawton and Brody (IADL), the FIQ questionnaire, and no standardized surveys to assess the pre and post intervention situation. An intervention on motor skills (basic motor skills, pool exercise, outdoor exercise, restructuring, occupational performance and graded activity and intervention in ADL) was performed, combining pharmacological control of their symptoms and treatment.
Results and conclusions:
Fibromyalgia patients are not fully satisfied with their treatment; Primary Care receives a score of 6.89, and Hospital Care 5.79, improving the Barthel, Lawton and Brody and FIQ indexes, being statistically significant (p<.05). After the combined procedure the number of independent women in ADL and IADL increases.
Telomere length is recognized as a marker of biological age, and shorter mean leukocyte telomere length is associated with increased risk of cardiovascular disease. It is unclear whether repeated exposure to ultra-endurance aerobic exercise is beneficial or detrimental in the long-term and whether it attenuates biological aging. We quantified 67 ultra-marathon runners' and 56 apparently healthy males' leukocyte telomere length (T/S ratio) using real-time quantitative PCR. The ultra-marathon runners had 11% longer telomeres (T/S ratio) than controls (ultra-marathon runners: T/S ratio = 3.5±0.68, controls: T/S ratio = 3.1±0.41; β = 0.40, SE = 0.10, P = 1.4×10(-4)) in age-adjusted analysis. The difference remained statistically significant after adjustment for cardiovascular risk factors (P = 2.2×10(-4)). The magnitude of this association translates into 16.2±0.26 years difference in biological age and approximately 324-648bp difference in leukocyte telomere length between ultra-marathon runners and healthy controls. Neither traditional cardiovascular risk factors nor markers of inflammation/adhesion molecules explained the difference in leukocyte telomere length between ultra-marathon runners and controls. Taken together these data suggest that regular engagement in ultra-endurance aerobic exercise attenuates cellular aging.
Triathletes and ironman triathletes engage in an extremely intense sport that involves hours of considerable pain, as well as physical and psychological stress, every day. The basic pain modulation properties of these athletes has not been established and therefore it is not clear whether they present with unique features that enable them to engage in such efforts. The aim was to investigate the existence of possible alterations in pain perception and modulation of triathletes, as well as possible underlying factors. Participants were 19 triathletes and 17 non-athletes who underwent the measurement of pain threshold, pain tolerance, suprathreshold perceived pain intensity, temporal summation of pain and conditioned pain modulation (CPM). Participants also completed the fear of pain and the pain catastrophizing questionnaires, and rated the amount of perceived stress. Triathletes exhibited higher pain tolerance (p<0.0001), lower pain ratings (p<0.001) and lower fear of pain values (p<0.05) than controls. The magnitude of CPM was significantly greater in triathletes (p<0.05), and negatively correlated with fear of pain (p<0.05) and with perceived mental stress during training and competition (p<0.05). The results suggest that triathletes exhibit greater pain tolerance and more efficient pain modulation than controls, which may underlie their perseverance in extreme physical efforts and pain during training/competitions. This capability may be enhanced or mediated by psychological factors, enabling better coping with fear of pain and mental stress.
Study design:
A cross-sectional study.
Objectives:
To investigate reliability, discriminative ability and concurrent validity of three functional tests (including the 10-meter walk test (10MWT), timed up and go test (TUGT) and five times sit-to-stand test (FTSST)) using the Functional Independence Measure Locomotor (FIM-L) scores as a standard criterion.
Setting:
A tertiary rehabilitation center, Thailand.
Methods:
Subjects were 66 patients with spinal cord injury (SCI), who were able to walk at least 50 m unassisted with or without a walking device (FIM-L scores 6-7). They were tested for functional ability using the 10MWT, TUGT and FTSST. Sixteen subjects also assessed the ability using three assessors to evaluate the inter-tester reliability of the tools.
Results:
The three functional tests demonstrated excellent inter-tester reliability (intraclass correlation coefficient (3,3)=0.997-1.00) and could clearly distinguish between subjects who walked with and without a walking device. In addition, the tests showed significant correlation with walking categories or FIM-L scores (r(pb)=0.778, -0.692 and -0.595 for the 10MWT, TUGT and FTSST, respectively, P<0.001).
Conclusion:
The findings support reliability and validity of the 10MWT, TUGT and FTSST to assess levels of independences in ambulatory subjects with SCI.
Long-term disorders are the main challenge facing health-care systems worldwide, but health systems are largely configured for individual diseases rather than multimorbidity. We examined the distribution of multimorbidity, and of comorbidity of physical and mental health disorders, in relation to age and socioeconomic deprivation.
In a cross-sectional study we extracted data on 40 morbidities from a database of 1,751,841 people registered with 314 medical practices in Scotland as of March, 2007. We analysed the data according to the number of morbidities, disorder type (physical or mental), sex, age, and socioeconomic status. We defined multimorbidity as the presence of two or more disorders.
42·2% (95% CI 42·1-42·3) of all patients had one or more morbidities, and 23·2% (23·08-23·21) were multimorbid. Although the prevalence of multimorbidity increased substantially with age and was present in most people aged 65 years and older, the absolute number of people with multimorbidity was higher in those younger than 65 years (210,500 vs 194,996). Onset of multimorbidity occurred 10-15 years earlier in people living in the most deprived areas compared with the most affluent, with socioeconomic deprivation particularly associated with multimorbidity that included mental health disorders (prevalence of both physical and mental health disorder 11·0%, 95% CI 10·9-11·2% in most deprived area vs 5·9%, 5·8%-6·0% in least deprived). The presence of a mental health disorder increased as the number of physical morbidities increased (adjusted odds ratio 6·74, 95% CI 6·59-6·90 for five or more disorders vs 1·95, 1·93-1·98 for one disorder), and was much greater in more deprived than in less deprived people (2·28, 2·21-2·32 vs 1·08, 1·05-1·11).
Our findings challenge the single-disease framework by which most health care, medical research, and medical education is configured. A complementary strategy is needed, supporting generalist clinicians to provide personalised, comprehensive continuity of care, especially in socioeconomically deprived areas.
Scottish Government Chief Scientist Office.
This study aimed to evaluate the immediate effects of a 6-mo combined exercise program on quality-of-life, physical function, depression, and aerobic capacity in women with fibromyalgia syndrome and to determine the impact of repeated delivery of the intervention.
Forty-one women with fibromyalgia were randomly assigned to a training group (EG; n = 21) and a control group (CG; n = 20). Quality-of-life and physical function were assessed using the 36-item Short-Form Health Survey (SF-36) and the Fibromyalgia Impact Questionnaire, and depression was measured using the Beck Depression Inventory. Physical fitness was measured using the 6-min Walk Test. Outcomes were assessed at baseline and after each 6-mo intervention, which was delivered over 30 mos (6 mos of training and 6 mos of detraining).
After a 6-mo combined exercise program, there was a significant improvement in the Fibromyalgia Impact Questionnaire (P < 0.0005) for the training group over the control group. Repeated-measures analysis of variance across all time points demonstrated significant main effects for time for the Fibromyalgia Impact Questionnaire, SF-36, Beck Depression Inventory and the 6-min Walk Test, but there were no between-group interaction effects. For the EG, there were significant within-group changes in the Fibromyalgia Impact Questionnaire, SF-36, and Beck Depression Inventory at the final time point; however, there were no within-group changes for the control group. Improvement achieved for the training group were maintained during the detraining period.
A long-term exercise program can produce immediate improvements in key health domains in women with fibromyalgia. The benefits achieved with regular training can be maintained for 30 mos. The lack of difference between groups over time may be caused by attrition and consequent lack of power at the final time point.
Central neuropathic pain (CNP) after spinal cord injury (SCI) is debilitating and immensely impacts the individual. CNP is relatively resistant to treatment administered after it develops, perhaps owing to irreversible pathological processes. Although preemptive treatment may overcome this shortcoming, its administration necessitates screening patients with clinically relevant biomarkers that could predict CNP early post-SCI. The aim was to search for such biomarkers by measuring pro-nociceptive and for the first time, anti-nociceptive indices early post-SCI.Participantswere 47 patients with acute SCI and 20 healthy controls (HC). Pain adaptation, conditioned pain modulation (CPM), pain temporal summation (TSP), windup pain, and allodynia were measured above, at, and below the injury level, at 1.5 months post-SCI. HC were tested at corresponding regions. SCI patients were monitored for CNP emergence and characteristics at 3-4, 6-7, and 24 months post-SCI.CNP prevalence was 57.4%. CNP severity, quality and aggravating factors but not location somewhat changed over 24 months. SCI patients who eventually developed CNP exhibited early, reduced at-level pain adaptation and CPM magnitudes than those who did not. The best predictor for CNP emergence at 3-4 and 7-8 months was at-level pain adaptation with odds ratios of 3.17 and 2.83, respectively (∼77% probability) and a cut-off value with 90% sensitivity. Allodynia and at-level CPM predicted CNP severity at 3-4 and 24 months, respectively.Reduced pain inhibition capacity precedes, and may lead to CNP. At-level pain adaptation is an early CNP biomarker with which individuals at risk can be identify to initiate preemptive treatment.
Cross-sectional study
To determine clinical factors associated with telomere length in persons with chronic spinal cord injury (SCI).
Veterans Affairs Medical Center, Boston, MA.
Two hundred seventy-eight participants with chronic SCI provided blood samples for measurement of C-reactive protein (CRP), interleukin-6 (IL-6), and telomere length, completed respiratory health questionnaires, underwent dual X-ray absorptiometry (DXA) to assess body fat, and completed spirometry. High-throughput real-time PCR assays were used to assess telomere length in leukocyte genomic DNA. Linear regression models were used to assess cross-sectional associations with telomere length.
Telomere length was inversely related to age (p < 0.0001). In age-adjusted models, gender, race, injury duration, %-total and %-trunk fat, body mass index (BMI), %-predicted forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), chronic cough or phlegm, CRP, IL-6, wheeze, smoking, diabetes, heart disease, chronic obstructive pulmonary disease (COPD), skin ulcer, urinary tract infection (UTI), or chest illness history were not significantly associated with telomere length. There was a suggestive age-adjusted association between persons with the most severe SCI (cervical motor complete and AIS C) and shorter telomere length (p = 0.055), an effect equivalent to ~8.4 years of premature aging. There were similar age-adjusted associations with telomere length between persons using a wheelchair (p = 0.059) and persons with chronic urinary catheter use (p = 0.082) compared to persons without these characteristics.
Our results suggest that clinical characteristics such as decreased mobility and bladder dysfunction that are common in individuals with more severe SCI are associated with shorter telomere length.
Chronic pain is a common, complex, and distressing problem that has a profound impact on individuals and society. It frequently presents as a result of a disease or an injury; however, it is not merely an accompanying symptom, but rather a separate condition in its own right, with its own medical definition and taxonomy. Studying the distribution and determinants of chronic pain allows us to understand and manage the problem at the individual and population levels. Targeted and appropriate prevention and management strategies need to take into account the biological, psychological, socio-demographic, and lifestyle determinants and outcomes of pain. We present a narrative review of the current understanding of these factors.
Abstract Chronic pain is associated with brain atrophy with limited evidence of its impact in the older adult’s brain. We aimed to determine the associations between chronic pain and a brain aging biomarker in persons 60 to 83 years old. Participants of the NEPAL study (n=47) completed demographic, psychological, and pain assessments followed by a QST battery and a T1-weighted MRI. We estimated a brain-predicted age difference that has been previously reported to predict overall mortality risk (brain-PAD; calculated as brain-predicted age minus chronological age), using an established machine-learning model. ANCOVAs and Pearson/Spearman correlations were used to determine associations of brain-PAD with pain, somatosensory and psychological function. Individuals with chronic pain (n=33) had “older” brains for their age compared to those without (n=14, F(1,41)=4.9,p=0.033). Greater average worst pain intensity was associated with an “older” brain (r=0.464,p=0.011). Among participants with chronic pain, those that reported having pain treatments during the past 3 months had “younger” brains compared to those that did not (F(1,27)=12.3, p=0.002). An “older” brain was significantly associated with decreased vibratory (r=0.323,p=0.033) and thermal (r=0.345,p=0.023) detection, deficient endogenous pain inhibition (F(1,25)=4.6,p=0.044), lower positive affect (r =-0.474,p=0.005), a less agreeable (r=-0.439,p=0.020), and less emotionally stable personality (r=-0.387, p=0.042). Our findings suggest that chronic pain is associated with added “age-like” brain atrophy in relatively healthy, community-dwelling older individuals and future studies are needed to determine the directionality of our findings. A brain aging biomarker may help identify people with chronic pain at greater risk of functional decline and poorer health outcomes.
The cardiovascular disease (CVD) pandemic has placed considerable strain on healthcare systems, quality of life, and physical function, while remaining the leading cause of death globally. Decades of scientific investigations have fortified the protective effects of cardiorespiratory fitness (CRF), exercise training, and physical activity (PA) against the development of CVD. This review will summarize recent efforts that have made significant strides in; 1) the application of novel analytic techniques to increase the predictive utility of CRF; 2) understanding the protective effects of long-term compliance to PA recommendations through large cohort studies with multiple points of assessment; 3) and understanding the potential harms associated with extreme volumes of PA.
Background:
Pain comorbid with depression is frequently encountered in clinical settings and often leads to significant impaired functioning. Given the complexity of comorbidities, it is important to address both pain and depressive symptoms when evaluating treatment options.
Aim:
To review studies addressing pain comorbid with depression, and to report the impact of current treatments.
Method:
A systematic search of the literature databases was conducted according to predefined criteria. Two authors independently conducted a focused analysis of the full-text articles and reached a consensus on 28 articles to be included in this review.
Results:
Overall, studies suggested that pain and depression are highly intertwined and may co-exacerbate physical and psychological symptoms. These symptoms could lead to poor physical functional outcomes and longer duration of symptoms. An important biochemical basis for pain and depression focuses on serotonergic and norepinephrine systems, which is evident in the pain-ameliorating properties of serotonergic and norepinephrine antidepressants. Alternative pharmacotherapies such as ketamine and cannabinoids appear to be safe and effective options for improving depressive symptoms and ameliorating pain. In addition, cognitive-behavioral therapy may be a promising tool in the management of chronic pain and depression.
Conclusion:
The majority of the literature indicates that patients with pain and depression experience reduced physical, mental, and social functioning as opposed to patients with only depression or only pain. In addition, ketamine, psychotropic, and cognitive-behavioral therapies present promising options for treating both pain and depression.
Physical activity is an important lifestyle factor for growth, development, and sustained health throughout life. In recent years, the benefits of physical activity have drawn more attention to its physiological effects on the body, including well-being. The endocannabinoid system (ECS) has emerged as a focal point to ascertain the mechanisms for how exercise benefits the body and how it reduces or controls pain. The ECS, its ligands [the endocannabinoids (eCB)], receptors (CB1 and CB2), enzymes for the synthesis and degradation of eCB, and the polyunsaturated fatty acids (PUFA) that serve as substrates, comprise a powerful biological organization of multiple controls that affects mood, inflammation, pain, and other neurological aspects of the central nervous system and peripheral nervous system. Recently, investigators have reported increases in circulating levels of eCB after exercise, with some eCB exerting analgesic effects from exercise. The focus of this review is to discuss evidence for the role of eCB and the complexities of the ECS in exercise and pain. Some aspects presented herein are production of eCB and activation of the cannabinoid receptors in the brain following exercise; eCB, pain, and physical activity; oxylipins; and joint pain. Future research on the ECS must include mechanistic approaches to endocannabinoid signaling and explain the role of dietary PUFA in altering signaling of the receptors that affects pain. Additionally, how other types of exercise, such as Tai Chi, which is reported to improve well-being, should be investigated to ascertain if changes in eCB mediate the mind and body benefits of Tai Chi. As we age, exercise in the form of play has evolved with the exploration of our body from walking to running, recreational, and competitive sports, to midlife physical activity focusing on maintaining fitness and a healthy body weight. Furthermore, exercise has been a target of investigation to explore various hypotheses to explain the mechanisms for cognitive benefits in the young and in older adults. The science of exercise has matured to a level of importance in the life cycle to reduce pain with aging and include new investigations on the ECS to explain its role in well-being and improved quality of life in later years.
Chronic pain is both prevalent and one of the leading causes of work-related disability. Somatic experiences of pain and pain interference with daily activities at work may lead to psychological distress and strain in workers. In accordance with the appraisal theory of stress, we proposed a model in which pain interference mid-workday predicts negative affect and end-of-workday emotional exhaustion in workers who interact with customers. Further, we proposed that pain interference predicts variance in negative affect and exhaustion beyond somatic experiences of pain, based on our theoretical proposition that pain interference represents a secondary stress appraisal. Participants (N = 86 full-time workers with chronic pain) completed 2 online surveys per day for 5 consecutive workdays. Results from multilevel path analysis supported our hypotheses; pain interference predicted both negative affect and end-of-day emotional exhaustion while controlling for somatic experiences of pain (pain severity). Further, pain interference indirectly predicted end-of-day emotional exhaustion via negative affect while controlling for somatic pain experiences. Results highlight the importance of pain interference as a stressor at work for individuals working with chronic pain and point to the need for effective interventions for this working population.
Peripheral nerve injury (PNI) activates the immune system resulting in increased pro-inflammatory cytokines at the site of injury and in the spinal cord dorsal horn. Exercise modulates the immune system promoting an anti-inflammatory phenotype of macrophages in uninjured muscle, and increases in anti-inflammatory cytokines can promote healing and analgesia. We proposed that PNI will decrease, and treadmill exercise will increase, release of anti-inflammatory cytokines at the site of injury and in the spinal cord. We show two weeks of treadmill exercise improves neuropathic pain behaviors in mice: mechanical hyperalgesia, escape/avoidance behavior, and spontaneous locomotor activity. PNI reduced anti-inflammatory cytokines (IL-4, IL-1ra, IL-5) at the site of nerve injury and in the spinal dorsal horn while exercise restored IL-4, IL-1ra, IL-5 concentrations to pre-injury levels. IL4 mice, and mice treated with IL-4 antibody did not develop analgesia to treadmill exercise. Using immunohistochemical staining of the sciatic nerve, treadmill exercise increased the percentage of M2-macrophages (secretes anti-inflammatory cytokines), and decreased M1-macrophages (secretes pro-inflammatory cytokines) when compared to sedentary mice. The increased M2 and decreased M1 macrophages in exercised mice did not occur in IL-4 mice. In the spinal cord, PNI increased glial cell activation, BDNF and β-NGF levels, and decreased IL-4 and IL-1ra levels while treadmill exercise suppressed glial cells activation (GFAP and Iba1 immunoreactivity), reduced BDNF and β-NGF, and increased IL-4, IL-1ra, IL-5. Our results suggest IL-4 mediates the analgesia produced by low-intensity exercise by modulating peripheral and central neuroimmune responses in mice with neuropathic pain.
Perspective:
The findings from the current study do not support the hypothesis that chronic pain accelerates cellular aging as measured by leukocyte telomere length. Additional population-based studies with more detailed assessments of pain and stress are needed to further investigate potential interactive effects on telomere length and other biomarkers of aging.
Regular physical activity prevents development of chronic muscle pain through modulation of central mechanisms that involve rostral ventromedial medulla (RVM). We tested if pharmacological blockade or genetic deletion of mu-opioid receptors in physically active mice modulates excitatory and inhibitory systems in the RVM in an activity-induced hyperalgesia model. We examined response frequency to mechanical stimulation of the paw, muscle withdrawal thresholds, and expression of phosphorylation of the NR1 subunit of the NMDA receptor (p-NR1) and serotonin transporter (SERT) in the RVM. Mice that had performed five days of voluntary wheel running prior to induction of the model were compared to sedentary mice. Sedentary mice show significant increases in mechanical paw withdrawal frequency and a reduction in muscle withdrawal threshold; wheel running prevented the increase in paw withdrawal frequency. Naloxone-treated and MOR-/- mice had increases in withdrawal frequency that were significantly greater than physically active controls, and similar to sedentary mice. Immunohistochemistry in the RVM showed increases in p-NR1 and SERT expression in sedentary mice 24h after induction of the model. Wheel running prevented the increase in SERT, but not p-NR1. Physically active naloxone-treated and MOR-/- mice showed significant increases in SERT immunoreactivity when compared to WT physically active control mice. Blockade of SERT in the RVM in sedentary mice reversed the activity-induced hyperalgesia of the paw and muscle. These results suggest that analgesia induced by 5 days of wheel running is mediated by of mu-opioid receptors through modulation of SERT, but not p-NR1, in RVM.
Introduction:. Individuals with osteoarthritis (OA) show increased morbidity and mortality. Telomere length, a measure of cellular aging, predicts increased morbidity and mortality. Telomeres shorten with persisting biological and psychosocial stress. Living with chronic OA pain is stressful. Previous research exploring telomere length in people with OA has produced inconsistent results. Considering pain severity may clarify the relationship between OA and telomeres.
Objectives:. We hypothesized that individuals with high OA chronic pain severity would have shorter telomeres than those with no or low chronic pain severity.
Methods:. One hundred thirty-six adults, ages 45 to 85 years old, with and without symptomatic knee OA were included in the analysis. Peripheral blood leukocyte telomere length was measured, and demographic, clinical, and functional data were collected. Participants were categorized into 5 pain severity groups based on an additive index of frequency, intensity, time or duration, and total number of pain sites (FITT). Covariates included age, sex, race or ethnicity, study site, and knee pain status.
Results:. The no or low chronic pain severity group had significantly longer telomeres compared with the high pain severity group, P = 0.025. A significant chronic pain severity dose response emerged for telomere length, P = 0.034. The FITT chronic pain severity index was highly correlated with the clinical and functional OA pain measures. However, individual clinical and functional measures were not associated with telomere length.
Conclusion:. Results demonstrate accelerated cellular aging with high knee OA chronic pain severity and provide evidence for the potential utility of the FITT chronic pain severity index in capturing the biological burden of chronic pain.
The principal objective was to determine the extent to which physical activity (PA) accounts for differences in leukocyte telomere length (LTL) in a large random sample of U.S. adults. Another purpose was to assess the extent to which multiple demographic and lifestyle covariates affect the relationship between PA and LTL. A total of 5823 adults from the National Health and Nutrition Examination Survey (NHANES 1999–2002) were studied cross-sectionally. Employing the quantitative polymerase chain reaction method, LTL was compared to standard reference DNA. PA was indexed using MET-minutes using self-reported frequency, intensity, and duration of participation in 62 physical activities. Covariates were controlled statistically. Telomeres were 15.6 base pairs shorter for each year of chronological age (F = 723.2, P < 0.0001). PA was inversely related to LTL after adjusting for all the covariates (F = 8.3, P = 0.0004). Telomere base pair differences between adults with High activity and those in the Sedentary, Low, and Moderate groups were 140, 137, and 111, respectively. Adults with High activity were estimated to have a biologic aging advantage of 9 years (140 base pairs ÷ 15.6) over Sedentary adults. The difference in cell aging between those with High and Low activity was also significant, 8.8 years, as was the difference between those with High and Moderate PA (7.1 years). Overall, PA was significantly and meaningfully associated with telomere length in U.S. men and women. Evidently, adults who participate in high levels of PA tend to have longer telomeres, accounting for years of reduced cellular aging compared to their more sedentary counterparts.
Unlabelled:
National Pain Strategy population research objectives include: estimating chronic pain prevalence, studying pain treatment with electronic health care data, and developing metrics to assess progress in reducing chronic pain impact. In this article, the National Pain Strategy Population Research Workgroup reviews concepts relevant to achieving these aims. High-impact chronic pain was defined as persistent pain with substantial restriction of life activities lasting 6 months or more. In pilot work, we tested a brief assessment of high-impact chronic pain, and used electronic health records data to describe pain-related health care. A mail survey of adult health plan enrollees (N = 770) reported that 14% had high-impact chronic pain. Relative to persons with lower-impact chronic pain, those with high-impact chronic pain were more often frequent users of health care for pain, reported lower quality of life, greater pain-related interference with activities, and more often reported pain at multiple anatomic locations. Analyses of health care data (N = 289,464) reported that pain patients had higher health care costs compared with others and that pain services were typically delivered in primary care. These results support the feasibility of developing data on chronic pain through national health interview surveys and large electronic health care databases.
Perspective:
Pilot analyses supported the feasibility of brief chronic pain assessments suitable for national health surveys and use of electronic health care databases to develop data regarding trends in the delivery of pain treatments, costs, and effectiveness. These methods are relevant to achieving the aims of the US National Pain Strategy.
The epidemic of opioid abuse is related in part to incomplete understanding of pain-relief management, opioid tolerance, and opioid addiction. Among the prevention strategies are more widespread sharing of data about opioid neuropharmacology and opioid-use patterns.
Importance
Primary care clinicians find managing chronic pain challenging. Evidence of long-term efficacy of opioids for chronic pain is limited. Opioid use is associated with serious risks, including opioid use disorder and overdose.Objective
To provide recommendations about opioid prescribing for primary care clinicians treating adult patients with chronic pain outside of active cancer treatment, palliative care, and end-of-life care.Process
The Centers for Disease Control and Prevention (CDC) updated a 2014 systematic review on effectiveness and risks of opioids and conducted a supplemental review on benefits and harms, values and preferences, and costs. CDC used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess evidence type and determine the recommendation category.Evidence Synthesis
Evidence consisted of observational studies or randomized clinical trials with notable limitations, characterized as low quality using GRADE methodology. Meta-analysis was not attempted due to the limited number of studies, variability in study designs and clinical heterogeneity, and methodological shortcomings of studies. No study evaluated long-term (≥1 year) benefit of opioids for chronic pain. Opioids were associated with increased risks, including opioid use disorder, overdose, and death, with dose-dependent effects.Recommendations
There are 12 recommendations. Of primary importance, nonopioid therapy is preferred for treatment of chronic pain. Opioids should be used only when benefits for pain and function are expected to outweigh risks. Before starting opioids, clinicians should establish treatment goals with patients and consider how opioids will be discontinued if benefits do not outweigh risks. When opioids are used, clinicians should prescribe the lowest effective dosage, carefully reassess benefits and risks when considering increasing dosage to 50 morphine milligram equivalents or more per day, and avoid concurrent opioids and benzodiazepines whenever possible. Clinicians should evaluate benefits and harms of continued opioid therapy with patients every 3 months or more frequently and review prescription drug monitoring program data, when available, for high-risk combinations or dosages. For patients with opioid use disorder, clinicians should offer or arrange evidence-based treatment, such as medication-assisted treatment with buprenorphine or methadone.Conclusions and Relevance
The guideline is intended to improve communication about benefits and risks of opioids for chronic pain, improve safety and effectiveness of pain treatment, and reduce risks associated with long-term opioid therapy.
Objectives:
Chronic pain may increase the risk of cardiac disease, but the extent to which confounding variables account for this association has yet to be satisfactorily established. This study aims to examine the possibility of an independent association between these 2 variables.
Methods:
We applied logistic regression analysis to data from 8596 adults surveyed in a population study of the health of the population of England. The association between cardiac disease (angina and/or myocardial infarction) and chronic pain (pain lasting >3 months) was explored, taking account of 10 potentially confounding variables including the regular use of nonsteroidal anti-inflammatory drugs.
Results:
Participants reporting chronic pain (n=3023) were more likely to experience cardiac disease than those without pain: odds ratio (OR), 1.55; 95% confidence interval (CI), 1.15-2.07. Subsets of participants fulfilling various criteria for high-intensity chronic pain demonstrated stronger associations with cardiac disease suggesting a "dose-response" element to the relationship: chronic widespread pain (OR, 3.3; 95% CI, 1.42-7.68); higher-disability chronic pain (OR, 2.35; 95% CI, 1.71-3.23); and higher average chronic pain score (OR, 1.95; 95% CI, 1.40-2.71). Adjustment for regular prescription of nonsteroidal anti-inflammatory drugs did not reduce the association of chronic pain with cardiac disease.
Discussion:
Patients reporting chronic pain, in particular those most severely affected, may be at significantly increased risk of cardiac disease. Future studies should focus on determining whether reducing the impact of chronic pain can improve cardiac health.
This study examined the association between leukocyte telomere length-a marker of cell aging-and mortality in a nationally representative sample of US adults ages 50-84 years. We also examined moderating effects of age, sex, race/ethnicity, and education.
Data were from the National Health and Nutrition Examination Survey, 1999-2002 (n = 3,091). Cox proportional hazards regression was used to estimate the risk of all-cause and cause- specific mortality adjusting for sociodemographic characteristics, smoking, body mass index, and chronic conditions.
Eight hundred and seventy deaths occurred over an average of 9.5 years of follow-up. In the full sample, a decrease of 1 kilobase pair in telomere length at baseline was marginally associated with a 10% increased hazard of all-cause mortality (hazard ratio [HR]: 1.1, 95% confidence interval [CI]: 0.9, 1.4) and a 30% increased hazard of death due to diseases other than cardiovascular disease or cancer (HR: 1.3, 95% CI: 0.9, 1.9). Among African-American but not white or Mexican-American respondents, a decrease of 1 kilobase pair in telomere length at baseline was associated with a two-fold increased hazard of cardiovascular mortality (HR: 2.0, 95% CI: 1.3, 3.1). There was no association between telomere length and cancer mortality.
The association between leukocyte telomere length and mortality differs by race/ethnicity and cause of death.
Chronic pain broadly encompasses both objectively defined conditions and idiopathic conditions that lack physical findings. Despite variance in origin or pathogenesis, these conditions are similarly characterized by chronic pain, poor physical function, mobility limitations, depression, anxiety, and sleep disturbance, and they are treated alone or in combination by pharmacologic and non-pharmacologic approaches, such as physical activity (aerobic conditioning, muscle strengthening, flexibility training, and movement therapies). Physical activity improves general health, disease risk, and progression of chronic illnesses such as cardiovascular disease, type 2 diabetes, and obesity. When applied to chronic pain conditions within appropriate parameters (frequency, duration, and intensity), physical activity significantly improves pain and related symptoms. For chronic pain, strict guidelines for physical activity are lacking, but frequent movement is preferable to sedentary behavior. This gives considerable freedom in prescribing physical activity treatments, which are most successful when tailored individually, progressed slowly, and account for physical limitations, psychosocial needs, and available resources.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Short telomeres in peripheral blood leukocytes are associated with older age and age-related diseases. We tested the hypotheses that short telomeres are associated with both increased cancer mortality and all-cause mortality.
Individuals (n = 64637) were recruited from 1991 onwards from two Danish prospective cohort studies: the Copenhagen City Heart Study and the Copenhagen General Population Study. All had telomere length measured by quantitative polymerase chain reaction and the genotypes rs1317082 (TERC), rs7726159 (TERT), and rs2487999 (OBFC1) determined. The sum of telomere-shortening alleles from these three genotypes was calculated. We conducted Cox regression analyses and instrumental variable analyses using the allele sum as an instrument. All statistical tests were two-sided.
Among 7607 individuals who died during follow-up (0-22 years, median = 7 years), 2420 had cancer and 2633 had cardiovascular disease as causes of death. Decreasing telomere length deciles were associated with increasing all-cause mortality (P trend = 2*10(-15)). The multivariable-adjusted hazard ratio of all-cause mortality was 1.40 (95% confidence interval [CI] = 1.25 to 1.57) for individuals in the shortest vs the longest decile. Results were similar for cancer mortality and cardiovascular mortality. Telomere length decreased 69 base pairs (95% CI = 61 to 76) per allele for the allele sum, and the per-allele hazard ratio for cancer mortality was 0.95 (95% CI = 0.91 to 0.99). Allele sum was not associated with cardiovascular, other, or all-cause mortality.
Short telomeres in peripheral blood leukocytes were associated with high mortality in association analyses. In contrast, genetically determined short telomeres were associated with low cancer mortality but not with all-cause mortality.
© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
[Two of the authors respond:]
We agree with Herbert Nehrlich that there are many situations in which physicians would benefit from the assistance of health and fitness professionals. It is essential that such advice be sought from professionals who have received formal training and attained national accreditation. In North America1 these would be professionals certified by the Canadian Society for Exercise Physiology or the American College of Sports Medicine. Together, physicians and health and fitness professionals will be able to provide information that is based on sound physiological principles and a clear knowledge of the absolute and relative contraindications to exercise for a variety of populations.
Giuseppe Lippi and associates correctly point out that vigorous exercise may lead to supplemental health gains in sedentary community-dwelling individuals. There is growing evidence to suggest that certain groups may benefit greatly from high-intensity exercise training. We1 have advocated high-intensity exercise training for sedentary individuals2 and patients with cardiovascular disease3 and chronic heart failure.4 However, we are careful to acknowledge that adherence to this form of exercise may be poor and the risk of musculoskeletal injury higher. Therefore, we must weigh carefully the potential advantages and disadvantages of vigorous exercise for each individual client.
As pointed out by Ediriweera Desapriya and colleagues, discussion of the barriers to exercise and innovative means to deliver inclusive and culturally appropriate physical activity interventions is of great importance. Furthermore, more effective lifestyle interventions are required to address the global crisis of physical inactivity. We have worked diligently to address the barriers to physical activity and have taken a transdisciplinary approach to the creation of novel exercise interventions. More work is required to “develop and deliver” inclusive interventions for all, but we believe that our work1,5 is a step in the right direction.
As Rajesh Chauhan and associates point out, the determinants of health are multifactorial and physical activity is not the sole factor influencing health status. However, physical inactivity is an independent predictor of the risk for many chronic diseases and premature mortality. In fact, the risk for chronic disease and premature mortality in North America appears to be about 20% to 50% greater among those with a physically inactive lifestyle.5 Furthermore, physical activity appears to be protective in the presence of other known risk factors for chronic disease. Therefore, there is compelling evidence to support the independent health benefits of physical activity.
Background:
Exercise is an effective treatment strategy in various chronic musculoskeletal pain disorders, including chronic neck pain, osteoarthritis, headache, fibromyalgia and chronic low back pain. Although exercise can benefit those with chronic pain (CP), some patients (eg, those with fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome and chronic whiplash associated disorders) encounter exercise as a pain inducing stimulus and report symptom flares due to exercise.
Objectives:
This paper focuses on the clinical benefits and detrimental effects of exercise in patients with CP. It summarizes the positive and negative effects of exercise therapy in migraine and tension-type headache and provides an overview of the scientific evidence of dysfunctional endogenous analgesia during exercise in patients with certain types of CP. Further, the paper explains the relationship between exercise and recovery highlighting the need to address recovery strategies as well as exercise regimes in the rehabilitation of these patients. The characteristics, demands and strategies of adequate recovery to compensate stress from exercise and return to homeostatic balance will be described.
Methods:
narrative review.
Results:
Exercise is shown to be effective in the treatment of chronic tension-type headache and migraine. Aerobic exercise is the best option in migraine prophylaxis, whereas specific neck and shoulder exercises is a better choice in treating chronic tension-type headache. Besides the consensus that exercise therapy is beneficial in the treatment of CP, the lack of endogenous analgesia in some CP disorders should not be ignored. Clinicians should account for this when treating CP patients. Furthermore, optimizing the balance between exercise and recovery is of crucial merit in order to avoid stress-related detrimental effects and achieve optimal functioning in patients with CP.
Conclusion:
Exercise therapy has found to be beneficial in CP, but it should be appropriately and individually tailored with emphasis on prevention of symptom flares and applying adequate recovery strategies.
In general, our findings in army special operations personnel
provide additional evidence of an association of LTL with PTSD,
in accordance with the previous observations in the civilian
population,1 and support the hypothesis that traumatic stress may
result in not only PTSD but also cellular aging. In addition, the
relative shortening of LTL among some PTSD patients compared
with controls suggests that cellular aging may occur in some PTSD
subjects but not all. The nature of this relationship warrants
further study.
Physical activity may play an important role in the management of mild-to-moderate mental health diseases, especially depression and anxiety. Although people with depression tend to be less physically active than non-depressed individuals, increased aerobic exercise or strength training has been shown to reduce depressive symptoms significantly. However, habitual physical activity has not been shown to prevent the onset of depression. Anxiety symptoms and panic disorder also improve with regular exercise, and beneficial effects appear to equal meditation or relaxation. In general, acute anxiety responds better to exercise than chronic anxiety. Studies of older adults and adolescents with depression or anxiety have been limited, but physical activity appears beneficial to these populations as well. Excessive physical activity may lead to overtraining and generate psychological symptoms that mimic depression. Several differing psychological and physiological mechanisms have been proposed to explain the effect of physical activity on mental health disorders. Well controlled studies are needed to clarify the mental health benefits of exercise among various populations and to address directly processes underlying the benefits of exercise on mental health.
Objective:
To provide a systematic review of the relationship between age and leukocyte telomere length (LTL) in adults.
Methods:
Relevant studies were identified by a systematic search of Medline, EMBASE and ISI Web of Knowledge databases. Key data, such as age and LTL, were extracted from the studies along with correlation coefficients and yearly attrition rates where available. Obtained data were used to calculate weighted means and correlation coefficients.
Results:
Overall, 124 cross-sectional studies and 5 longitudinal studies were identified. A statistically significant inverse correlation between mean age and mean LTL across cross-sectional studies was observed for both absolute (r=-0.338, p<0.0001) and relative LTL (r=-0.295, p=0.0088). From mean LTL and ages, a yearly telomere loss of 24.7 base pairs (BP)/year was estimated by weighted linear regression. Weighted means of within study correlation of age and TL and yearly telomere loss rate estimates from cross-sectional studies were also in a similar order of magnitude (-0.380 and 21.91 BP/year). The few longitudinal studies reported somewhat higher mean telomere loss rates (between 32.2 and 45.5 BP/year).
Conclusion:
While a decrease of LTL with age is out of question, data on variation of the decrease according to sex, age and other potential determinants especially from longitudinal data are still sparse.
Accumulation of life stressors predicts accelerated development and progression of diseases of aging. Telomere length, the DNA-based biomarker indicating cellular aging, is a mechanism of disease development, and is shortened in a dose response fashion by duration and severity of life stressor exposures. Telomere length captures the interplay between genetics, life experiences and psychosocial and behavioral factors. Over the past several years, psychological stress resilience, healthy lifestyle factors, and social connections have been associated with longer telomere length and it appears that these factors can protect individuals from stress-induced telomere shortening. In the current review, we highlight these findings, and illustrate that combining these `multisystem resiliency' factors may strengthen our understanding of aging, as these powerful factors are often neglected in studies of aging. In naturalistic studies, the effects of chronic stress exposure on biological pathways are rarely main effects, but rather a complex interplay between adversity and resiliency factors. We suggest that chronic stress effects can be best understood by directly testing if the deleterious effects of stress on biological aging processes, in this case the cell allostasis measure of telomere shortening, are mitigated in individuals with high levels of multisystem resiliency. Without attending to such interactions, stress effects are often masked and missed. Taking account of the cluster of positive buffering factors that operate across the lifespan will take us a step further in understanding healthy aging. While these ideas are applied to the telomere length literature for illustration, the concept of multisystem resiliency might apply to aging broadly, from cellular to systemic health.
Rheumatologic diseases (e.g., fibromyalgia, osteoarthritis, and rheumatoid arthritis) consist of a complex interplay between biologic and psychological aspects, resulting in therapeutically challenging chronic conditions to control. Encouraging evidence suggests that Tai Chi, a multi-component Chinese mind-body exercise, has multiple benefits for patients with a variety of chronic disorders, particularly those with musculoskeletal conditions. Thus, Tai Chi may modulate complex factors and improve health outcomes in patients with chronic rheumatologic conditions. As a form of physical exercise, Tai Chi enhances cardiovascular fitness, muscular strength, balance, and physical function. It also appears to be associated with reduced stress, anxiety, and depression, as well as improved quality of life. Thus, Tai Chi can be safely recommended to patients with fibromyalgia, osteoarthritis, and rheumatoid arthritis as a complementary and alternative medical approach to improve patient well-being. This review highlights the current body of knowledge about the role of this ancient Chinese mind-body medicine as an effective treatment of rheumatologic diseases to better inform clinical decision-making for our patients.
Unlabelled:
Telomere length, considered a measure of biological aging, is linked to morbidity and mortality. Psychosocial factors associated with shortened telomeres are also common in chronic pain; yet, little is known about telomere length in pain populations. Leukocyte telomere length was evaluated in 66 women with fibromyalgia and 22 healthy female controls. Participants completed questionnaires and a subgroup of fibromyalgia patients underwent quantitative sensory testing (QST; n = 12) and neuroimaging (n = 12). Telomere length was measured using the quantitative polymerase chain reaction method. Although patients had shorter telomere length than controls, the difference was not statistically significant. However, higher levels of pain within fibromyalgia were associated with shorter telomere length (P = .039). When pain and depression were combined, patients categorized as high-pain/high-depression had an age-adjusted telomere length 265 base pairs shorter than those with low-pain/low-depression (P = .043), a difference consistent with approximately 6 years of chronological aging. In the subset tested, telomere length was also related to pain threshold and pain sensitivity, as well as gray matter volume, such that patients with shorter telomeres were more sensitive to evoked pain and had less gray matter in brain regions associated with pain processing (eg, primary somatosensory cortex). These preliminary data support a relationship between pain and telomere length.
Perspective:
Our findings support a link between premature cellular aging and chronic pain. These preliminary data imply that chronic pain is a more serious condition than has typically been recognized in terms of bodily aging.
Depression has been likened to a state of “accelerated aging,” and depressed individuals have a higher incidence of various diseases of aging, such as cardiovascular and cerebrovascular diseases, metabolic syndrome, and dementia. Chronic exposure to certain interlinked biochemical pathways that mediate stress-related depression may contribute to “accelerated aging,” cell damage, and certain comorbid medical illnesses. Biochemical mediators explored in this theoretical review include the hypothalamic–pituitary–adrenal axis (e.g., hyper- or hypoactivation of glucocorticoid receptors), neurosteroids, such as dehydroepiandrosterone and allopregnanolone, brain-derived neurotrophic factor, excitotoxicity, oxidative and inflammatory stress, and disturbances of the telomere/telomerase maintenance system. A better appreciation of the role of these mediators in depressive illness could lead to refined models of depression, to a re-conceptualization of depression as a whole body disease rather than just a “mental illness,” and to the rational development of new classes of medications to treat depression and its related medical comorbidities. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc.