Leena Mathew, MD, ASA Committee on Pain Medicine, Associate Professor, Department of Anesthesiology, and Program Director of Pain Medicine Fellowship, Columbia University Medical Center, New York, New York. Twitter handle: @lmathew9001

Leena Mathew, MD, ASA Committee on Pain Medicine, Associate Professor, Department of Anesthesiology, and Program Director of Pain Medicine Fellowship, Columbia University Medical Center, New York, New York. Twitter handle: @lmathew9001

Chronic pain is a life-disrupting experience. Despite its commonplace occurrence and advancements in therapeutic interventions, patients struggle to find adequate relief and to improve functionality. According to a 2016 National Health Interview Survey (NHIS) 20.4% of U.S. adults have chronic pain, and 8% (19.6 million) of adults have high-impact chronic pain (Vital Health Stat 2 2017;1-22). There is higher prevalence of both in older unemployed adults and in those living in poverty and/or with public health insurance (Fam Pract 2001;18:292-9). These socio-economic indicators correlate with poor access to and less success with navigating the health care system (Pain 2017;158:313-22). This year, COVID-19 has drawn attention to racial-socio-economic disparities correlated with disproportionate impact of the disease (N Engl J Med 2020;383:201-3). The pandemic also highlights the importance of metabolic health, as patients with modifiable conditions like obesity, coronary disease, hypertension, cerebrovascular disease, and diabetes have higher morbidity and mortality from COVID (Diabetes Metab Syndr 2020;14:809-14).

Chronic pain typically occurs with markers linked to many chronic illnesses and has an increased risk of all-cause related mortality (Disabil Rehabil 2009;31:1980-7). These co-occurrences may have common metabolic, inflammatory, or genetic etiologies or be the unfortunate consequences of health inequities. This loop of chronic pain and co-morbidities intersects with several modifiable factors (obesity, poor posture, inactivity, stress, poor nutrition) (Pain Res Manag 2011;16:87-92). Forty percent of deaths in the U.S. are connected to these life-impairing modifiable factors (PLoS Med 2009;6:e1000058). Despite this appalling statistic, lifestyle change is daunting for patients in pain with psycho-social and physical limitations. This is where health coaching enhances care. Health coaching improves concurrent disease management, perceived quality of care, and satisfaction, particularly in patients with socio-economic barriers to health care (Am J Manag Care 2015;21:685-91). Those who undergo health coaching identify it as a positive experience that enhances their health-related actions and access. Health coaching decreases pain perception, improves functionality, improves glycemic control, decreases body mass index (BMI)and reduces diabetic distress (Am J Manag Care 2015;21:685-91; Prev Chronic Dis 2017;14:E21; Scand J Med Sci Sports 2015;25 S3:1-72). Additionally, coaching helps improve sleep and mitigate fatigue and stress (Work 2019;63:49-56). With our knowledge regarding the morbidity of chronic pain and the need to improve metabolic health, value-guided lifestyle changes should be foundational in treatment.

Inflammatory changes at a cellular level are intrinsic to pain and chronic diseases. During the initial inflammatory phase, M1 macrophages stimulate cytokines, tumor necrosis factor α (TNF-α), interleukins (IL)-1,-12, interferon γ (IFγ), inducible nitric oxide synthase (iNOS), and reactive oxygen species (ROS), mediators that form the groundwork for tissue degeneration, matrix degradation, and sensitization. Pro-resolving lipid mediators (lipoxins, resolvins, protectins, and maresins) counter inflammation through a series of cellular events: M1 macrophages convert to M2 phenotype, which release anti-inflammatory chemokines, IL-10, transforming growth factor β (TGF-β), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and vascular epithelial growth factor (VEGF). M2 macrophages deplete chemokines through cleavage by MMP and promote matrix synthesis and tissue remodeling (Rheumatology (Oxford) 2018;57:429-40).

Metabolic syndrome (MetS) is characterized by obesity, hyperglycemia, hypertriglyceridemia, decreased serum high-density lipoprotein, and hypertension (Dis Model Mech 2009;2:231-7). MetS is common in several chronic pain conditions such as fibromyalgia, neuropathy, osteo-arthritis, migraine, and spinal and pelvic pain (Metabolism 2007;56:87-93). Hyperglycemia and obesity both contribute to the pro-inflammatory state of MetS. High blood sugar levels activate toll-like receptors (TLR) and receptors for advanced glycation end products (RAGE) to trigger slow cytokine release (Am J Physiol Renal Physiol 2012;303:F1145-50). Meanwhile, obese tissue alters iNOS expression to release pro-inflammatory iNO (1,2) isoforms that are toxic in glia, neurons, macrophages, and endothelium, processes implicated in migraines, Alzheimer's and Parkinson's disease. White adipose tissue acts as an active endocrine organ releasing leptin, TNF-a, and adipokines, which induce cytokine release from T helper-1 cells, recruit M1 macrophages, stimulate B-cells and mast cells, and IgG release. Cell signaling by adipokines mediates insulin resistance (Clin Endocrinol (Oxf) 2006;64:355-65; Immunotargets Ther 2016;5:47-56). Additionally, obesity creates mechanical stresses that break down cartilage matrix, which along with adipokine-induced IL,TNFα, and NOS signal synovial degeneration and chondrocyte death linked to many arthropathies (Pain 2011;152:53-9; Rheumatology (Oxford) 2015;54:588-600). Adipokines shift the balance of serotonin/kynurenine production from tryptophan in favor of kynurenine, with the reduced serotonin levels contributing to depression (J Neuroinflammation 2014;11:151). Nuclear factor kappa B (NF-Kβ) increases with obesity, hyperleptinemia, and increased advanced glycosylated end products (AGE). NF-Kβ promotes tumorigenesis and releases pro-inflammatory cyclooxygenase-2(COX-2), TNF-a, IL-1β, and IL-6 (Cell Metab 2011;13:11-22). Contrastingly, adiponectin from brown adipose tissues supports insulin sensitivity and attenuates inflammation through M2 macrophage recruitment and anti-inflammatory cytokines (IL)-4,10,13 activity. Adiponectin levels are increased by fat loss, decreasing blood glucose, and increasing aerobic exercise (Int J Mol Sci 2017;18:1321).

Nutrigenetic studies indicate that our genetic makeup directs our response to food. Nutrition is a key modifiable factor that impacts DNA methylation and histone modifications to alter transcriptional machinery and regulate the epigenome. Supplementation with micronutrients (folate, niacin, vitamins B12 and E, retinol, calcium, and sulfurophanes) can decrease oxidative DNA damage and improve cellular health (Nutrients 2018;10:1618). Contrarily, caloric excess is implicated with increased oxidative stress, cellular inflammation, and cellular aging (Sci Transl Med 2015;7:304re7). NF-K-β mediated inflammaging is decreased by nutrients like resveratrol, quercetin, curcumin, omega 3 fatty acid (FA), and polyphenols. Decrease in NF-Kβ can occur with caloric restriction, fasting, aerobic exercise, and decreasing fat mass (Cell Metab 2011;13:11-22). In the future, ongoing nutrigenomic studies may guide creation of individualized omics profiles to prescribe precise nutritional interventions.

Dietary interventions may reduce pain. Elimination of food triggers, including gluten, nightshade vegetables, lectins, and lactose is common in arthropathies, abdominal pain, and migraines. A high-fermentable oligo-di-monosaccharides and polyols (FODMAP) environment changes the gut-biome, increases gut permeability, and decreases absorption of tryptophan (Trp)-yielding low serotonin. Low FODMAP diets (LFD) activate Meissner's plexus, modulates neuro-enteric sensory transmission, increases serotonin production, and increases motility. The decrease in pain improves function and quality of life measures in fibromyalgia, IBS, migraines, and depression (Gastroenterology 2007;132:397-414; Neuropsychiatr Dis Treat 2017;14:21-8). Increasing dietary omega-3 potentiates pro-resolution mediators and has a favorable profile in arthritis and cardiovascular diseases states. Studies recommend optimal intake of omega-3:6 ratio of 5. Reversal of this ratio dysregulates endothelial function and glial activity and induces M1 macrophages (J Clin Rheumatol 2017;23:330-9). Epidemiological studies demonstrate an increased omega-6 intake is also associated with poor cognitive performance and higher inflammatory markers (World Rev Nutr Diet 2011;102:92-7).

Overwhelming evidence shows that sedentarism causes sarcopenia, obesity, and other diseases. On the other hand, physical activity mitigates cellular inflammation and improves mitochondrial function, insulin sensitivity, and cardiorespiratory fitness. Increase in exercise-induced brain-derived neurotrophic factor (BDNF) signaling pathways contributes to learning and memory formation and offers protection from neuro-degeneration. Flexibility and movement therapies (yoga, Tai Chi, and Qigong) can improve mood, pain, QOL, function, balance, mobility, and flexibility (Cochrane Database Syst Rev 2017;4:CD011279). Physical activity seems to be essential for healthspan and lifespan.

Clearly, we want our patients to eat better, move more, and lose weight. Our patients also want the same, so why is this elusive? Unfortunately, the burden of co-morbidities, polypharmacy, and disability disempower patients and makes disease management challenging. Despite national guidelines calling for “healthy living,” most physicians are limited by time or expertise to coach. If physicians espouse preventive behaviors as a post-script, then the cursory instructions become a low priority for patients who struggle with lifestyle change and adherence to a program. Since patients differ in strengths and limitations, lasting change is more likely in an individualized coaching paradigm with group educational sessions provided by trained coaches or physician who has a coaching-minded approach. At the core of coaching is its patient-centrism: meeting patients where they are in their readiness to change. Rather than “telling,” there should be collaboration to define self-determined specific, measurable, attainable, realistic time-bound (SMART) goals. Instead of a directive “be more active,” coaching may encourage a patient to identify a SMART goal: “I will walk 20 minutes, three days per week on Monday, Wednesday, and Friday for two weeks.” Accomplishing small goals can increase self-efficacy and motivation for larger intentional change. Asking patients simple, open-ended questions like “what do you have to do?” “how can you do this?” and “why is this important?” brings patients clarity in understanding their ambivalence and creates an attainable vision for their own health. It also provides space to formulate strategies to overcome potential obstacles. Meeting the health goals of improved BMI, sleep, stress, nutrition, and exercise amplifies treatment adherence and well-being while positively impacting function and pain perception.

Chronic pain is inextricably linked to several chronic diseases and lifestyle factors that add to disease burden. We should venture beyond standardized therapies to target the modifiable elements that can improve metabolic health and well-being. Health coaching facilitates co-creative and bidirectional therapeutic encounters that maximize patients' health potential. Successful behavioral change has the potential to lessen the burden of chronic disease and increase health literacy and access to care while improving patient satisfaction within the health care system.