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Opioid Alternatives for Chronic Pain

African-American woman rubbing her temples

Approximately 20% of adults (~50 million) in the US are affected by chronic pain, defined as pain on most days or every day in the past six months. In addition, an estimated 8% of US adults (~20 million) experience high-impact chronic pain, which limits life or work activities for the same duration.1 “For millions of people across the globe, excruciating pain is an inescapable reality of life,” writes Allyn L. Taylor in a 2007 article published in The Journal of Law, Medicine & Ethics.2 Does it have to be this way?

Many turn to opioids for relief. However, research shows that the extended prescription of opioids for the treatment of chronic pain has questionable benefits and significant risks that include the following:3

  • Constipation and abdominal pain
  • Tolerance – physiologic adaptation
  • Physiologic dependence and withdrawal
  • Opioid misuse
  • Depression
  • Hormonal dysregulation
  • Opioid-induced hyperalgesia
  • Cardiovascular events
  • Suppressed breathing and accidental overdose

In the article below, we explore some nonpharmacological treatments to chronic pain, which include targeting the mitochondria and modifying diet.

Opioid Alternative – Targeting Mitochondria

Our objectives are to recognize the process of how centralized pain syndromes develop, to recall the key metabolic factors that influence chronic pain states, and to apply the Functional Medicine Timeline and Matrix in the assessment and treatment of these syndromes.

Specifically, Dr. Portera-Perry encourages clinicians to understand the relationship between mitochondrial function and chronic pain.

Dr. Lisa Portera-Perry, DC, is a passionate advocate for Functional Medicine and its application for patients and has worked extensively on the development of programs related to dietary and lifestyle modifications as applied to pain syndromes.

Mitochondria have a variety of essential functions within neurons.4 Studies have shown that the five major mitochondrial functions (the mitochondrial energy generating system, reactive oxygen species generation, mitochondrial permeability transition pore, apoptotic pathways, and intracellular calcium mobilization) may play critical roles in neuropathic and inflammatory pain.5

Although this area of pain research is relatively new, mitochondrial dysfunction has been confirmed in both chronic pain patients and in animal models of chronic pain.4 Substantial data have demonstrated mitochondrial involvement in painful peripheral neuropathies evoked by chemotherapy, diabetes, and HIV.4 For some patients, supporting mitochondrial function may be a promising strategy to alleviate or prevent chronic pain states.5

Mitochondria produce 95% of cellular energy and play a critical role in protecting the cell from oxidative stress. Lifestyle and environmental stressors can alter mitochondrial function and cause the onset of disease processes within the body. As a first step in enhancing mitochondrial stability, Functional Medicine clinicians can prescribe the Mitochondrial Food Plan, an anti-inflammatory, low-glycemic, gluten-free, low-grain, high-quality fats approach to eating. The plan, which was developed through the combined efforts of a team consisting of Functional Medicine physicians, leading experts, and nutrition professionals, focuses on supporting healthy mitochondria with therapeutic foods that improve energy production.

No two pain patients are the same; every pain patient has a unique underpinning—a unique pattern of neurological and mitochondrial change, so we want to widen our lens and broaden our thinking. Pain unravels in many layers.

-- Dr. Lisa Portera-Perry, DC

Opioid Alternative – Nutrition

The Functional Medicine model provides guidance to clinicians looking to treat pain patients through modifiable lifestyle factors like diet. A 2019 systematic review suggests that nutrition interventions may have a significant impact on pain reduction, with altered overall diets and changes in specific nutrients having the greatest effects.6 Some of these interventions may work by altering mitochondrial function, although the exact mechanisms have not yet been elucidated.

Inflammation, the Elimination Diet, & Food Reactions
There is increasing evidence that diet can contribute to systemic inflammation,7 and pain perception is commonly related to inflammatory stimulus and mediators.8 The most explored dietary triggers for chronic pain include cow’s milk antigens (??lactalbumin, ??lactoglobulin, casein), wheat and wheat gluten, eggs, and soy proteins.7 Because food intolerances and allergies can be challenging to diagnose, and testing for these disorders is variable in terms of sensitivity and specificity, many researchers believe that elimination diets are the gold standard for diagnosis of food reactions.9-11 Encouraging wholesome eating is an essential part of chronic pain management, along with investigating possible immune reactivity to food.12-14

Chronic Musculoskeletal Pain
Dietary markers, including low fruit and vegetable consumption, have been identified for inflammatory arthritis.13 The journal Rheumatology published a study that found that a gluten-free, vegan diet may improve the signs and symptoms of rheumatoid arthritis (RA).7 A raw, vegan diet, rich in antioxidants and fiber, was shown in another study to decrease joint stiffness and pain in patients with RA.15 A 2018 study suggested consumption of a plant-based diet decreased pain and improved quality of life for subjects with reported chronic musculoskeletal pain; however, the study was small, with only 14 participants, the results were based solely on self-reporting, and no control group was used.16

A 2019 study suggests that vitamin D deficiency may be associated with lower back pain.17 Supplementation with vitamin D (to sufficient serum vitamin D level) in these patients may increase mitochondrial function and inhibit muscle atrophy, according to the study authors. It may also have a beneficial impact on an effective early rehabilitation in lower back pain patients. Future studies should look at patients with different BMI and age for a better understanding of the mechanisms of vitamin D function.17

Interstitial Cystitis
Few studies, to date, examine the role of diet in interstitial cystitis/bladder pain syndrome (IC/BPS), but more and more research is beginning to accrue. Based on a 2012 review, anecdotal reports and questionnaire-based surveys suggest that in patients with IC/BPS, nearly 90% experience sensitivities to a variety of foods.18 In BJU International, Friedlander et al report that citrus fruits, tomatoes, vitamin C, artificial sweeteners, coffee, tea, carbonated and alcoholic beverages, and spicy foods may exacerbate symptoms, while calcium glycerophosphate and sodium bicarbonate may improve symptoms. Furthermore, the authors write that a controlled method to determine dietary sensitivities, such as the elimination diet, could play an important role in defining optimal modifications.18

A promising report in 2017 found that intensive systematic dietary manipulation alleviated the symptoms of IC/BPS in women after three months of intervention, with continued clinical efficacy for at least one year.19 More recently, in a 2019 study on bladder pain syndrome published in Primary Care, Huffman et al report that for patients, dietary changes (avoiding acidic, spicy, and caffeinated foods) are effective at relieving symptoms.20

Researchers have also begun looking at ways to modulate the urinary tract microbiome with probiotics/prebiotics and diet to improve health.21

Fibromyalgia and Central Sensitization
A 2015 review in Clinical and Experimental Rheumatology found that among non-pharmacological treatments for chronic pain, nutrition may be a promising tool for fibromyalgia syndrome patients.22 One study showed that in fibromyalgia patients with celiac disease, more than one-third of patients who removed gluten from their diet were able to discontinue opioid therapy for chronic pain.23 In chronic pain patients with central sensitization, including those with whiplash, temporomandibular disorders, lower back pain, osteoarthritis, and fibromyalgia, among others, a study found that the ketogenic diet may diminish the hyper-excitability of the central nervous system.24

Research into the role of nutrition and the mitochondria in modulating chronic pain continues to accrete. How can these therapies be integrated into the Functional Medicine protocol for treating pain patients? Learn more at IFM’s Bioenergetics Advanced Practice Module.

Learn More About Mitochondrial Function

For more information on treatment for chronic pain syndromes, please read the following IFM-authored articles:

Controlling pain in autoimmune patients

Chronic pain and the brain with Dr. Dave Hagedorn

Making connections: chronic pain, stress, and addiction

References
  1. Dahlhamer J, Lucas J, Zelaya C, et al. Prevalence of chronic pain and high-impact chronic pain among adults – United States 2016. MMWR Morb Mortal Wkly Rep. 2018;67(36):1001-1006. doi:10.15585/mmwr.mm6736a2
  2. Taylor AL. Addressing the global tragedy of needless pain: rethinking the United Nations single convention on narcotic drugs. J Law Med Ethics. 2007;35(4):556-570,511. doi:10.1111/j.1748-720X.2007.00180.x
  3. Lembke A, Humphreys K, Newmark J. Weighing the risks and benefits of chronic opioid therapy. Am Fam Physician. 2016;93(12):982-990.
  4. Flatters SJ. The contribution of mitochondria to sensory processing and pain. Prog Mol Biol Transl Sci. 2015;131:119-146. doi:10.1016/bs.pmbts.2014.12.004
  5. Sui BD, Xu TQ, Liu JW, et al. Understanding the role of mitochondria in the pathogenesis of chronic pain. Postgrad Med J. 2013;89(1058):709-714. doi:1136/postgradmedj-2012-131068
  6. Brain K, Burrows TL, Rollo ME, et al. A systematic review and meta-analysis of nutrition interventions for chronic noncancer pain. J Hum Nutr Diet. 2019;32(2):198-225. doi:10.1111/jhn.12601
  7. Hafström I, Ringertz B, Spångberg A, et al. A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Rheumatology. 2001;40(10):1175-1179. doi:10.1093/rheumatology/40.10.1175
  8. Ronchetti S, Migliorati G, Delfino DV. Association of inflammatory mediators with pain perception. Biomed Pharmacother. 2017;96:1445-1452. doi:10.1016/j.biopha.2017.12.001
  9. Wood RA. Diagnostic elimination diets and oral food provocation. Chem Immunol Allergy. 2015;101:87-95. doi:10.1159/000371680
  10. Dupont C. Diagnosis of cow’s milk allergy in children: determining the gold standard? Expert Rev Clin Immunol. 2014;10(2):257-267. doi:10.1586/1744666X.2014.874946
  11. Ballmer-Weber BK. Value of allergy tests for the diagnosis of food allergy. Dig Dis. 2014;32(1-2):84-88. doi:10.1159/000357077
  12. Seaman DR. The diet-induced proinflammatory state: a cause of chronic pain and other degenerative diseases? J Manipulative Physiol Ther. 2002;25(3):168-179. doi:10.1067/mmt.2002.122324
  13. Vandenkerkhof EG, Macdonald HM, Jones GT, Power C, Macfarlane GJ. Diet, lifestyle and chronic widespread pain: results from the 1958 British Birth Cohort study. Pain Res Manag. 2011;16(2):87-92. doi:10.1155/2011/727094
  14. Totsch SK, Waite ME, Sorge RE. Dietary influence on pain via the immune system. Prog Mol Biol Transl Sci. 2015;131:435-469. doi:10.1016/bs.pmbts.2014.11.013
  15. Hänninen O, Kaartinen K, Rauma AL, et al. Antioxidants in vegan diet and rheumatic disorders. Toxicology. 2000;155(1-3):45-53. doi:10.1016/S0300-483X(00)00276-6
  16. Towery P, Guffey JS, Doerflein C, Stroup K, Saucedo S, Taylor J. Chronic musculoskeletal pain and function improve with a plant-based diet. Complement Ther Med. 2018;40:64-69. doi:10.1016/j.ctim.2018.08.001
  17. Dzik KP, Skrobot W, Kaczor KB, et al. Vitamin D deficiency is associated with muscle atrophy and reduced mitochondrial function in patients with chronic low back pain. Oxid Med Cell Longev. 2019;2019:6835341. doi:10.1155/2019/6835341
  18. Friedlander JI, Shorter B, Moldwin RM. Diet and its role in interstitial cystitis/bladder pain syndrome (IC/BPS) and comorbid conditions. BJU Int. 2012;109(11):1584-1591. doi:10.1111/j.1464-410X.2011.10860.x
  19. Oh-Oka H. Clinical efficacy of 1-year intensive systematic dietary manipulation as complementary and alternative medicine therapies on female patients with interstitial cystitis/bladder pain syndrome. Urology. 2017;106:50-54. doi:10.1016/j.urology.2017.02.053
  20. Huffman MM, Slack A, Hoke M. Bladder pain syndrome. Prim Care. 2019;46(2):213-221. doi:10.1016/j.pop.2019.02.002
  21. Aragón IM, Herrera-Imbroda B, Queipo-Ortuño MI, et al. The urinary tract microbiome in health and disease. Eur Urol Focus. 2018;4(1):128-138. doi:10.1016/j.euf.2016.11.001
  22. Rossi A, Di Lollo AC, Guzzo MP, et al. Fibromyalgia and nutrition: what news? Clin Exp Rheumatol. 2015;33(1 Suppl 88):S117-S125.
  23. Isasi C, Colmenero I, Casco F, et al. Fibromyalgia and non-celiac gluten sensitivity: a description with remission of fibromyalgia. Rheumatol Int. 2014;34(11):1607-1612. doi:10.1007/s00296-014-2990-6
  24. Nijs J, Malfliet A, Ickmans K, Baert I, Meeus M. Treatment of central sensitization in patients with ‘unexplained’ chronic pain: an update. Expert Opin Pharmacother. 2014;15(12):1671-1683. doi:10.1517/14656566.2014.925446

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