Chronic Pain : The Gut-Joint Axis

Chronic pain is a significant health issue, and it is estimated that one-half of those suffering with chronic pain have been suffering for longer than 10 years.^[1] An estimated 54.4 million North Americans have been diagnosed with various arthritic disorders,^[2] conditions that are typically treated with nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs work by inhibiting proinflammatory molecules called cytokines like interleukin 6 (IL 6), tumor necrosis factor alpha (TNFα), and prostaglandins.^[3]

It is widely known that prolonged usage of NSAIDs like Advil and Tylenol over the long term create side effects such as ulcers, gastrointestinal (GI) bleeding, heartburn, bloating, and gas.^[4] NSAIDs are also known to contribute to hyperpermeability of the GI tract, or leaky gut syndrome.^[5] This can lead to the development of allergies, small bacterial overgrowth syndrome, and irritable bowel syndrome, among other digestive diseases.

Alternative health professionals are often asked to support various chronic pain conditions like osteoarthritis (OA) and rheumatoid arthritis (RA), often without access to medications for pain control but more often to heal the body from the damage of using these medications. Given the prevalence of joint inflammation in irritable bowel diseases (IBD),^[6][7] and the general prevalence of chronic pain and GI imbalances in aging, it is imperative that our understanding of the gut-joint axis becomes a crucial part of our management of disease, as opposed to pain elimination alone.^[5][6]

Microbiome Status in Chronic Joint Pain

The GI tract is widely understood to be our first line of defence against foreign invaders, through a combination of beneficial commensal bacteria and strong epithelial integrity.^[8] The proper ratio of “good” flora creates balanced immunity; the presence of higher amounts of lactic-acid bacteria, such as Lactobacilli and Bifidobacteria, positively influence T helper regulatory cells which control immune reactivity in IBS, chronic pain, and reactive arthritis.^[9][10][11] In contrast, GI tracts with higher colonies of possible pathogens, such as Clostridia or Klebsiella, may contribute to joint disease.^[12][13][14] Outside of the GI tract, cross-reactivity reactions can form between host tissue bacterial antigens, leading to the production of autoantibodies and triggering inflammatory cascades within the synovium.^[12]

Consumption of probiotics containing lactic-acid bacteria such as S. thermophilus, L. bulgaricus, L. acidophilus, or Bifidobacterium bifidus haS been associated with reduction of reactive arthritis in animal models of arthritis,^[12][15][16] and both probiotics and prebiotics (inula, flax) have been shown to impact musculoskeletal disorders in human patients.^[12] However, not all “good” bacteria guarantee healthy joints. Bacterial overgrowth of the small intestine can promote the development of joint pain and systemic fibromyalgia-like syndromes. In animal models of RA, rats who were kept in sterile conditions did not develop the disease until they were exposed to normal bacterial colonies and their colons were able to grow “normal” bacterial flora.^[15][17] Only after this did they develop synovitis, or joint inflammation. Germ-free rats have also been shown to have reduced gut and joint inflammation.^[18] Therefore, the key is keeping bacterial flora in the right ratios, properly balanced between cellular-mediated immunity (Th1) and humoral immunity (Th2).^[19] Two key strategies address this line of thought: proper nutrition and stress-hormone regulation.

Nutritional Support for Arthritis

Vegetarian-type diets that are rich in fibre, antioxidants like seabuckthorn and elderberry, and beneficial bacteria through fermented foods like sauerkraut and pickling for Lactobacillus, might reduce pain, thereby improving quality of life in RA patients.^[23][24] With respect to OA, similar results can be seen with consumption of avocado and soy vegetable extracts, with patients seeing increased joint mobility and movement, and prevention and inhibition of joint-cartilage degradation.^[25] Further research is needed to determine mechanisms and specific dietary ratios that are optimal for pain reduction.

Food Sensitivities and Joint Inflammation

No specific foods have been clearly identified to eat to alleviate chronic pain, but rather foods to avoid. Sugar, for example, has been linked with increased risk for the development of RA.^[20] It is also known that simple carbohydrates influence gut microbiota: In both humans and animal models, a Western diet (high fat / high sugar) has been shown to enhance counts of disease-contributing species (Firmicutes) and decrease counts of beneficial bacterial (Bacterioidetes) species.^[21][22] Undiagnosed food allergies and/or intolerances can be inflammatory triggers for chronic pain in the musculoskeletal system. Because food intolerances and allergies can be challenging to diagnose, and testing for these disorders is variable in terms of sensitivity and specificity (especially for intolerances of the IgG classes),^[26] elimination diets are still the current gold-standard for diagnosis. Clinically speaking, reduced cow’s dairy is promising, and the most commonly explored triggers include cow’s milk antigens (α lactalbumin, β lactoglobulin, casein), wheat and wheat gluten, eggs (ovalbumin), and soy proteins. A case study in 1981 revealed dairy elimination reduced pain, stiffness, and grip strength in a patient with RA,^[27] and a randomized controlled trial of 94 RA patients showed that elimination of milk protein in a subset of patients with dairy allergy improved their disease activity.^[28] Blood-serum testing for these sensitivities is a challenge. A group exploring food intolerances in patients with the autoimmune skin condition Sjögren’s disease investigated increased reactivity in the anal area (rectum) in response to consumption of cow’s milk protein in 8 of the 21 patients.^[30] Many of these patients also had IBS symptoms, and a few were also sensitive to gluten.

Influence of Stress Hormones on the Gut-Joint Axis

Chronic pain itself is a physically and emotionally taxing condition. Managing stress hormones should be a significant component of treatment, especially considering the fact that chronic pain decreases quality of life, not only through changed activity levels and physical restrictions, but also by the depression and anxiety that can often develop in tandem.^[31] We know from research that the stress hormone cortisol can compromise the health of the intestine.^[32] Serotonin decreases in stress, while cortisol increases.^[33] Being that over 90% of serotonin is produced in the gut, when people are craving carbohydrates to increase serotonin, they may be indirectly creating more inflammation due to weight gain or the types of foods they choose to reduce this craving. Overweight OA patients have been found to have higher levels of pain compared to normal-weight individuals, and also to experience symptom relief from eating high-fat / high-sugar foods.^[31][34] Reduced amounts of the stress hormone cortisol is also a problem. Chinese medicine describes this as kidney yang deficiency (cold, aching body, exhaustion, diarrhea, IBS like conditions), which has been shown in an animal model to be treated effectively with herbal medicine.^[35] What is fascinating is that Curcuma longa (turmeric) and its extract curcumin, well-known for its ability to improve chronic pain in most musculoskeletal conditions,^[36][37][38] may also decrease stress hormone. In animal models of chronic constrictive pain, as often seen in neuropathic pain disorders in humans, hypersensitivity to pain (hyperalgesia) and cortisol levels were reduced with curcumin consumption.^[39] Downregulation of IL 6, TNFα, and IL 1β, key mediators in inflammatory pain and immune chronic upregulation, are seen with curcumin interventions in similar animal models.^[40] Curcumin is also able to influence Western diet–induced inflammation.^[41]

Herbal Medicine and the Gut-Joint Axis

Boswellia serrata, also known as Indian frankincense, is a wonderful pain-relieving herb for joint inflammation, but is also intensely healing for GI disease and OA.^[42][43] It has also been shown to heal the lining of the gastrointestinal tract against previous damage and to protect against further damage in IBD.^[44] It is relatively inexpensive, and there are good ethical sources of this resin available commercially. Rehmannia glutinosa, utilized for many centuries in Chinese medicine as a cortisol regulator, adaptogen (stress-modulator), and mediator in autoimmunity, has been shown in rat models to reduce chronic neuropathic pain in a dose-dependent manner.^[43]

Conclusion

That many individuals are seeking out nutritional or herbal treatments to support or reduce dependence on pharmaceutical pain intervention for chronic pain is encouraging. We are forced, again, to look at the root causes of pain expression, rather than to merely palliate, despite our ability to do so and our personal desire to alleviate suffering. By continuing to focus on the gut-joint axis, we are led to more successful management of chronic pain.