Chronic Disease Pain Management through use of the Endocannabinoid System

Chronic Disease Pain Management Using the Endocannabinoid System
Margo R. Flanagan
American College of Healthcare Sciences
July 22, 2018

Abstract
Chronic disease and management of the accompanying neuropathic and nociceptive pain presents with significant treatment challenges, places a considerable cost burden on the current healthcare system and reduces overall quality of life and productivity for millions of Americans.
Chronic and persistent pain from autoimmune diseases such as Rheumatic disease, Fibromyalgia and Diabetes Mellitus interferes with everyday normal activities while the chronic inflammatory state causes tissue damage and progression of disease. Current treatment options such as opioids and corticosteroids can have significant side effects with long term usage. Phytocannabinoids, working with the Endocannabinoid system are emerging as a safe and effective treatment for chronic pain and inflammation. This case study details a 58 year old woman diagnosed with fibromyalgia, DM and RA looking to manage chronic pain through the use of endocannabinoids.

Introduction
Eila, a 58 year old woman diagnosed with Rheumatoid Arthritis (RA), Fibromyalgia and Diabetes Mellitus Type II (DM) is experiencing debilitating pain interfering with her everyday normal activities. Eila is prescribed Metformin, Nortriptyline, Lyrica and Methotrexate. Every few months a corticosteroid is needed to treat an acute flare. She is compliant with her medication but feels she has reached a plateau needing higher doses to achieve adequate pain relief and normal blood glucose levels. Eila would like to improve her overall quality of life and health, decrease the daily pharmaceuticals and learn to manage her chronic pain using a holistic approach.
Eila’s last physical exam by her primary care physician revealed less than desirable results associated to symptomatic pain, secondary hypertension and diabetes. Eila’s pain. Eila’s Hemoglobin A1C%, which averages blood sugar over a two to three month period is higher than normal. Increases in C-reactive protein (CRP), a biomarker produced in the liver are seen in chronic inflammatory states, more so with comorbidity, high BMI and disturbances in sleep (Feinberg, Sambamoorthi, Lilly & Innes, 2017). Her PCP recommended Eila begin working with a holistic practitioner certified in integrative medicine.

Overview of Nociceptive and Neuropathic Pain
Acute pain is a physiological response of the body by an event that activates a signaling pathway to the brain. This in turn triggers a self-limiting response to repair tissue damage (Fine & Rosenfeld, 2013). Nociceptive pain results from activation of peripheral nerves. These nerves convey signals through a pain pathway, up through the spinal cord ending in the brain. Neuropathic pain results from damaged or malfunctioning components of the central nervous system often seen in conditions such as Multiple Sclerosis. Neuropathic pain is difficult to treat due to corresponding hyperalgesia and allodynia (Barrie & Manolios 2017). Pain from arthritis and diabetic peripheral neuropathy is both nociceptive and neuropathic making it very difficult to treat (Barrie & Manolios, 2017).
Pain that does not subside and becomes chronic reduces quality of life, social activity, productivity and presents a significant cost burden on the current healthcare system. Chronic pain reorganizes the central nervous system circuits and pain nexus causing difficult to treat hyperalgesia and allodynia states (Barrie & Manolios, 2017). Results from clinical trials show that less than half of patients with chronic pain find relief with current pharmacotherapy (Fine & Rosenfeld 2013). There is a growing need for alternative methods to reduce pain and inflammation from chronic disease without significant side effects or addictive properties.

Overview of the Endocannabinoid System
The promising therapeutic potential of the Endocannabinoid system has become an area of focused research alongside the movement to legalize marijuana. Although the therapeutic use of cannabis for pain dates back over three thousand years (Pacher Batkai & Kunos, 2006), it is only within the last decade, with the discovery of the action mechanism of endogenous cannabinoids, CB1 and CB2 cannabinoid receptors and accompanying enzymes that new perspectives for treating chronic pain have emerged (Dhopeshwarker & Mackie, 2014).
The Endocannabinoid System (ECS) is believed to be a part of all mammals, fish, birds and amphibians (Dhopeshwarker & Mackie, 2014) interacting with the body’s pain system and inflammatory pathways (Russo, 2008). Endocannabinoids, mainly anandamide (AEA) and 2-arachidonoylglycerol (2-AG), G-protein coupled receptors CB1 and CB2 and enzymes responsible for cleavage of endocannabinoids into signaling molecules are the main components of the ECS. Mapping of these constituents has been found throughout the nociceptive pathway. Signaling along the pathway is regulated by CB1 receptors in the central nervous system and brain and CB2 receptors in the periphery and on immune cells. The anti-nociceptive effects result from the regulation of neurotransmitters in the synapses and inhibition of certain mediators of inflammation (Barrie & Manolios, 2017).

Phytocannabinoids
β-carophyllene is the primary sesquiterpene found in copaiba essential oil, oregano, cinnamon, black pepper, clove, rosemary, carrots and cannabis (Gertsch et al, 2008).
Copaiba essential oil, containing high amounts of β-carophyllene is able to modulate inflammatory processes (Guimarães-Santos et al., 2012).

Treatment of the Patient
During Eila’s first visit with her holistic practitioner (HP) they discussed how losing weight by increasing daily movement would help move her current values into a more desirable range. Eila’s compliance and positive attitude about improving her overall quality of life were an asset to achieving her health and wellness goals. Eila also had a great support network including a close friend interested in attending a weekly yoga class. Conversations with others in the yoga class surrounded topics of organic food recipes, meditation and the current cannabis regulations. Specifically, Eila had overheard a conversation about the therapeutic benefits of CBD oil.
The HP discussed the impact of stress, poor sleep hygiene and inflammatory foods on her pain level and recommended Eila begin journaling her daily routine including exercise, diet, sleep, stress and pain levels in order to find trends between them.

Discussion
Research results
Patients with fibromyalgia have found significant reductions in pain levels after use of cannabis products (Russo, 2008).
The use of cannabis has been linked with decreased incidence of obesity, Diabetes Mellitus, insulin resistance and lower body mass index (Penner, Buettner, Murray & Mittleman, 2013).
Piperine extracted from black pepper exhibits anti-nociceptive and anti-arthritic effects through inhibition of the enzymes 5-lipoxygenase and COX-1 found in the inflammatory pathways (Bang et al., 2008).
The analgesic effects of orally administered β-carophyllene are exhibited in its reduction of neuropathic pain, promotion of TH1 immune response and inhibition of the pathways that produce the pro-inflammatory cytokines, IL-1, IL-6 IL, IL-8 and TNF-α (Fine & Rosenfeld, 2013).

Conclusion
A holistic approach to improving health allowed Eila to successfully lower her weight, blood pressure, hemoglobin A1C, C-reactive protein and pain level through lifestyle modifications and the introduction of phytocannabinoids. Eila had many prior unsuccessful attempts at losing weight when it was centered on a vigorous exercise routine because her pain interfered with consistent activity throughout the week. The introduction of yoga improved the symptoms of fibromyalgia. Through journaling, Eila was able to ascertain that certain foods, mainly dairy and red meat increased her pain while meditating and yoga improved her mental and emotional health and sleep habits.

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