Sub-Acute Pain and Healing Support with Nutraceutical and Lifestyle Recommendations

Sub-Acute Pain and Healing Support with Nutraceutical and Lifestyle Recommendations

Pain is the number #1 reason why people enter the system. Pharmacists get questions about pain management strategies on a daily basis regardless of their setting. This is one of the reasons we choose pain and inflammation to be our next symposium topic for FxMedCE.com. We want more providers to understand the types of pain and how to help our patients. I hope you enjoy another great blog post from Dr. Frank Bodnar, DC. He is will be one of the speakers, make sure you sign up to hear from him as well as others who have spoken across the globe. Continuing Education Credit is available for Pharmacists and Certified Nutrition Specialists (CNS). Others are welcome to join!

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One of the most overlooked phases of pain and healing is the sub-acute phase. There’s some uncertainty about how to best approach sub-acute pain from a pharmacist’s perspective since it’s not really acute, and it’s not chronic. Often this puts patients in a “no-man’s-land” of self-management with no clear direction of where we want them to go and why, so patients do what they’ve always done. They go back to the medicine cabinet for another pain reliever. 

Helping patients navigate the middle ground of pain and healing presents a fantastic opportunity where pharmacists can help prevent the cycle of pill dependency for pain. This shift allows the body to do the healing. After all the injury didn’t occur by a deficiency in ibuprofen or acetaminophen and won’t fully support the body’s middle phase of structural healing if the cycle continues. The cycle of dependency may lead the patient down a road of more potent like a cortisone injection or even a prescription opioid. Pharmacists can alter this trajectory.

The majority of the time the sub-acute phase of care is treated with the exact same approach as an acute phase, despite there being clear physiologic differences. It’s understandable that there is some overlap between the acute and sub-acute phases and major guidelines may overlook the need for a different approach.  

Traditionally the American College of Physiciansrecommends a number of both pharmaceutical and non-pharmaceutical options for sub-acute low back pain,¹and within the realm of therapies available there are a number of other options available as well:

• Cryotherapy
• Heat
• Electrotherapy
• Ultrasound
• Low level laser
• TENS Machine
• Electrical Stimulation
• Spinal manipulation
• Massage
• Acupuncture
• Dry needling
• Kinesio taping
• Instrument assisted soft tissue mobilization
• Exercise rehabilitation
• Anti-inflammatory drugs
• Topical analgesic 
• Skeletal muscle relaxants

While all of the therapies listed above are traditionally appropriate in the management of sub-acute pain and healing, they are primarily focused on symptom management and leave out nutrition completely. Healing is a complex process that requires proper key nutrients for inflammatory control, new tissue formation, and tissue remodeling to occur within a specific time frame to get back to optimal function. Simply reaching for the bottle in the medicine cabinet isn’t sufficient.

In some cases, all three phases of the healing process may take 12-18 months to be fully completed depending on the tissue type and injury severity.²Managing patient expectations is an essential part of pain management. If patients understand the phases of healing and goal of therapies at each phase, you can begin to provide the roadmap to a pain-free future.

During sub-acute pain the focus of the body with many injuries is connective tissue repair and rebuilding structural integrity. Connective tissue regeneration and repair begins with fibroblasts producing type I and type III collagen fibers, which are randomly orientated, immature, and weak in comparison to the well-organized, dense fibers of type I collagen. Depending on the structure, type II collagen and extracellular matrix material like hyaluronic acid and other polysaccharides help to aggregate, organize and allow proper structure movement to occur.³

The remodeling phase requires gradual collagen and connective tissue cross-linking, which is dependent on the vital cofactor vitamin C. Vitamin C activates hydroxylases, allowing proper collagen fiber assembly and helical structure formation to occur.⁴If connective tissue alignment and aggregation is limited, collagen fiber orientation remains disorganized and overall function remains limited. This area will likely be a site of reinjury, and vitamin C plays a key role in preventing this.⁵

Clinical studies on nutraceuticals as bioactive collagen peptides, type I collagen, hyaluronic acid and essential cofactors for collagen formation have shown they not only reduce rehabilitation time, but also endogenously stimulate chondrocytes, fibroblasts and synovial cells to produce their native raw materials. In addition, these studies also show reduced cytokines such as IL-1β, which stimulate a class of connective tissue-degrading enzymes called matrix metalloproteinases (MMPs) .^6-8Structural support and inflammatory support at the cellular level are essential to reducing the risk of re-injury in all connective tissues.

The best nutraceuticals to offer patients during a sub-acute pain episode is a combination of high-quality type I and type II collagen peptides, hyaluronic acid, mucopolysaccharides, vitamin C and magnesium. These nutrients cover over 90% of the connective tissue in the body and undoubtedly would enhance he sub-acute phase of healing and repair. Not only do they support the connective tissue cells, the process of protein synthesis and collagen cross-linking but they also have clinical studies with positive clinical outcomes. Of course, sometimes simply offering an alternative to a muscle-relaxer may be appropriate as well. 

Tendinopathies are largely an overuse injury and represent a good example of what will also support connective tissue regeneration and repair during a sub-acute phase of pain and healing. A 2014 study out of Barcelona and Madrid, Spain treated tendinopathy patients at multiple hospitals and sports rehabilitation clinics around the area with high-quality type I collagen peptide that also contained vitamin C, magnesium and naturally occurring mucopolysaccharides. A total of 98 patients with Achilles tendinitis, patellar tendinitis and lateral epicondylitis received a dose of 435 mg mucopolysaccharides, 75 mg type I collagen peptides and 60 mg of vitamin C for 90 days. Clinical symptoms improved by 38% (during activity and rest) on average and a decrease in tendon thickness was observed upon ultrasound evaluation – indicating less inflammation and tendon hypertrophy.⁹

There are valid options available that get results and support the body during the healing process and your patients should be aware. Below are some key evidence-based sub-acute pain and healing nutraceuticals:

Nutrient	Dose	Mechanism
GABA10	250mg/day for 30 days	Primary inhibitory neurotransmitter of the brain promotes relaxation and inhibits over-firing that results in muscle spasm and pain. Also shown clinically to improve sleep, promote alpha brain waves and improve REM sleep cycle.
Glycine11	225mg/day for 30 days	Primary inhibitory neurotransmitter of the spinal cord promotes relaxation and inhibits over-firing that results in muscle spasm and pain, as well as promoting sleep quality.
Cramp Bark12	200mg/day for 30 days	Anti-inflammatory and promotes smooth muscle relaxing effects. Not only effective for muscle spasms of the neck and low back but has shown effectiveness with menstrual cramping as well.
Dong Quai Root Extract12	150mg/day for 30 days	Anti-inflammatory and promotes smooth muscle relaxing effects. Not only effective for muscle spasms of the neck and low back but has shown effectiveness with menstrual cramping as well.
Type I collagen peptides with mucopolysaccharides13-16	500 mg/day for 90-180 days	Type I collagen building block and stimulates tenocytes and fibroblasts to produce type I collagen in tendons, ligaments and skin. Clinical studies have shown improvement in medial and lateral epicondylitis, Achilles tendinitis and patellar tendinitis.
Type II collagen peptides17-19	5 g/day for 90-180 days	Type II collagen building block and stimulates chondrocytes and to produce type II collagen in cartilage and stimulates chondrocytes to endogenously produce more type II collagen.
Hyaluronic acid20-22	40-80 mg/day for 90-180 days	Increases hyaluronic acid concentration in synovial fluid and stimulates synoviocytes to increase HA production for joint and connective tissue hydration and lubrication. Clinical studies have shown improvements in pain scores, mobility and decreased synovitis in OA patients.
Vitamin C23	100 mg/day for 90-180 days	Maximizes hydroxylases for optimal collagen and hyaluronic acid production and provides antioxidant support to optimize connective tissue healing, decreases histamine production, modulates immune response and new studies show potential reduction of pain.
Magnesium24	135 mg/day for 90-180 days	Co-factor for over 350 enzymes in the body, decreases chronic pain signaling via NMDA receptors, and shown to decrease pain in low back and headache patients.

Supporting the body’s natural healing process is paramount and in some patients, this means digging a little deeper into lifestyle factors that can limit this process. The final missing variables in the sub-acute pain and healing equation is addressing the patient’s lifestyle by doing a quick evaluation of their stress levels and sleep quality. We know that the stress response can delay healing, and sleep is the primary time when the body is in repair mode. In a clinical trial published in Psychoneuroendocrinology, scientists looked at participants’ cortisol levels, perceived stress and health behaviors and how all of the factors affected wound healing. What they found was that cortisol had a considerable influence on wound healing independent of participants’ health behaviors. ²⁵ 

Multiple studies have also looked at sleep quality on healing, showing that poor sleep elevates cortisol, increases fatigue and errors made at work and results in worse patient health outcomes.^26,27In one study the health of patients recovering in hospitals revealed that sleep was crucial for healing and survival of critically ill patients and greatly influenced the outcomes of patients suffering from a myriad of diseases. In fact, less sleep disruptions in critically ill patients showed much better outcomes in the literature compared to those with constant disruptions from health care practitioners during their recovery time.²⁷       

Changing the patient’s perspective on pain and implementing easy nutrient and lifestyle recommendations doesn’t have to be a complicated process. There are cortisol tests and sleep study methods available, but many patients want an immediate solution that will allow them to improve immediately. Simply having a conversation about how to best serve a patient will reveal the best nutrient offering and implementing a 5-minute stress questionnaire can reveal how stress and sleep may be limiting the sub-acute healing process. Start by simply engaging patients and offering the best recommendation for their specific situation and you’ll put them on the path to letting he body do what it does best.

References:

1. Qaseem, A., Wilt, T., McLean, R., & Forciea, M. (2017). Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline from the American College of Physicians. Annals of Internal Medicine, 166(7), 514. 
2. Reichert, W., Stroncek, J., & Reichert, W. (2008). Indwelling Neural Implants: Strategies for Contending With the in Vivo Environment (Frontiers in neuroengineering)(Chapter 1: Overview of Wound Healing in Different Tissue Types). Boca Raton, FL: CRC Press.
3. Broughton, G., 2nd, J. E. Janis, et al. (2006). “The basic science of wound healing.” Plast Reconstr Surg 117(7 Suppl): 12S-34S
4. DePhillipo, N. N., Aman, Z. S., Kennedy, M. I., Begley, J. P., Moatshe, G., & LaPrade, R. F. (2018). Efficacy of Vitamin C Supplementation on Collagen Synthesis and Oxidative Stress After Musculoskeletal Injuries: A Systematic Review. Orthopaedic journal of sports medicine, 6(10), 2325967118804544. 
5. Ömeroğlu, S., Peker, T., Türközkan, N., & Ömeroğlu, H. (2008). High-dose vitamin C supplementation accelerates the Achilles tendon healing in healthy rats. Archives of Orthopaedic And Trauma Surgery, 129(2), 281-286. 
6. Iwai K, Hasegawa T, Taguchi Y, Morimatsu F, Sato K, Nakamura Y, Higashi A, Kido Y, Nakabo Y, Ohtsuki K, 2005. Identification of food-derived collagen peptides in human blood after oral ingestion of gelatin hydrolysates. J Agric Food Chem, 53, 6531-6536.
7. Oesser S, Adam M, Babel W, Seifert J, 1999. Oral administration of (14) C labeled gelatin hydrolysate leads to an accumulation of radioactivity in cartilage of mice (C57/BL). JNutr, 129, 1891-1895.
8. P. Lundquist, P. Artursson . Oral Absorption of peptides and nanoparticles across the human intestine. Advanced Drug Delivery Reviews106 (2016) 256–276
9. Arquer, A., et al. (2014). The efficacy and safety of oral mucopolysaccharide, type I collagen and vitamin C treatment in tendinopathy patients.
10. Yoto, A., et al. (2011). Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. Amino Acids, 43(3), pp.1331-1337. 
11. Kawai, N., et al. (2014). The Sleep-Promoting and Hypothermic Effects of Glycine are Mediated by NMDA Receptors in the Suprachiasmatic Nucleus. Neuropsychopharmacology, 40(6), pp.1405-1416. 
12. Nicholson, J. A., Darby, T. D., and Jarboe, C. H. Viopudial, a hypotensive and smooth muscle antispasmodic from Viburnum opulus. Proc.Soc. Exp Biol.Med. 1972;140(2):457-461) 
13. Schunk M and Oesser S. Specific collagen peptides benefit the biosynthesis of matrix molecules of tendons and ligaments. J Int Soc Sports Nutr. 2013; 108. 
14. Shakibaei M, Buhrmann C, Mobasheri A. Anti-inflammatory and anti-catabolic effects of TENDOACTIVE® on human tenocytes in vitro. Histol Histopathol. 2011 Sep;26(9):1173-85.
15. Balius et al. A Randomized, Placebo-Controlled Study to Evaluate Efficacy and Safety of A Dietary Supplement Containing Mucopolysaccharides, Collagen Type I and Vitamin C for Management of Different Tendinopathies. Ann Theum Dis. 2014;73, Suppl. 2:299- 30018. 
16. Proksch E, Oral intake of specific bioactive collagen peptides reduces skin wrinkles and increases dermal matrix synthesis. Skin Pharmacol Physiol. 2014;27(3):113-9. doi: 10.1159/000355523. 
17. McAlindon TE, Nuite M, Krishnan N, Ruthazer R, et al. Changes in knee osteoarthritis cartilage detected by delayed gadolinium enhanced magnetic resonance imaging following treatment with collagen hydrolysate: a pilot randomized controlled trial. Osteoarthritis and Cartilage19 (2011) 399e405 7.
18. Zuckley L, Angelopoulou K, Carpenter MR: Collagen hydrolysate improves joint function in adults with mild symptoms of osteoarthritis of the knee. Medicine and Science in Sports and Exercise 2004, 36 (Supplement), 153 – 155. 
19. Clark KL, Sebastianelli W, Flechsenhar KR, Aukermann DF, Meza F, Millard RL, Deitch JR, Sherbondy PS, Albert A: Long-term use of collagen hydrolysate as a nutritional supplement in athletes with activity-related joint pain. Curr Med Res Opin. 2008 May;24(5):1485-96.6.
20. Torrent A, Ruhí R, Theodosakis J, et al. Comparative efficacy of IB0004, extracted hyaluronic acid (HA) and fermented HA on the synthesis of endogenous HA by human synoviocytes. Osteoarthritis Cartilage. 2009;17(Suppl 1):S278-79. – 10x HA secretion9. 
21. Torrent A, Ruhí R, Martínez C, et al. Anti-inflammatoryactivity and absorption of a natural rooster comb extract. Osteoarthritis and Cartilage. 2010 Oct;18(Suppl 2):S246-47. 
22. Möller I, Martinez-Puig D, Chetrit C. Oral administration of a natural extract rich in hyaluronic acid for the treatment of knee OA with synovitis: a retrospective cohort study. Clinical Nutrition Supplements2009;4(2):171-17211
23. Carr, A., & McCall, C. (2017). The role of vitamin C in the treatment of pain: new insights. Journal of Translational Medicine, 15(1). doi: 10.1186/s12967-017-1179-7
24. Na HS, Ryu JH, Do SH. The role of magnesium in pain. In: Vink R, Nechifor M, editors. Magnesium in the Central Nervous System [Internet]. Adelaide (AU): University of Adelaide Press; 2011.
25. Ebrecht, M., Hextall, J., Kirtley, L., Taylor, A., Dyson, M., & Weinman, J. (2004). Perceived stress and cortisol levels predict speed of wound healing in healthy male adults. Psychoneuroendocrinology,29(6), 798-809. 
26. Niu, S., Chung, M., Chen, C., Hegney, D., O’Brien, A., & Chou, K. (2011). The Effect of Shift Rotation on Employee Cortisol Profile, Sleep Quality, Fatigue, and Attention Level. Journal of Nursing Research, 19(1), 68-81. 
27. Tembo, A., & Parker, V. (2009). Factors that impact on sleep in intensive care patients. Intensive and Critical Care Nursing, 25(6), 314-322.