LOCAL FRONTIERS Natural Agents for Musculoskeletal Conditions

The prevalence of musculoskeletal injuries and chronic musculoskeletal conditions is quite high compared with other medical disorders. In a classic study of adults, about 33% were found to have signs of a musculoskeletal condition on exam.[1] The highest prevalence was 15% for the back, followed by 12% for the knee. A more recent study found a similar 25% overall background prevalence of musculoskeletal symptoms in adults.[2] Injuries occurring in the context of sports had the highest prevalence.

The goal of this article is to present evidence for using herbal medications to treat musculoskeletal conditions. This requires some examination of the pathophysiology of inflammation and how the biochemical mechanisms of various nutrients and herbs can mitigate the inflammatory process and promote healing. Lest the reader think that use of natural agents is ancillary or incidental, we need to remind ourselves of the 1% to 2% of clinically significant upper GI events with NSAIDs. Of the 60 million Americans using NSAIDS on a regular basis, reports of NSAID-associated deaths range from 3,200 to 16,500 per year.[3]

Other concerns with NSAIDs include their negative effects on cartilage formation and renal function.[4] In addition, numerous references suggest that the benefit of NSAIDs in acute sports injuries may result in pain reduction without mitigating the inflammation or aiding the healing process.[5]

The anatomy of tendons is complex. The tenocytes are a very small component of tendons, which consist mainly of extracellular matrix, predominantly Type I collagen, 30% water and small amounts of elastin, proteoglycans and inorganic elements, including copper, manganese and calcium. The tenocytes manufacture collagen molecules, which align end-to-end and side-to-side to form fibrils, which combine to form the fibers of tendons.

Tendon pathology includes inflammation of the peritendinous sheath lying between the tendon and the tendon sheath; non-inflammatory injury or tendinosis; and tendinitis with inflammation of the tendon and disruption of the vascular supply. After injury, the tendon becomes inflamed, followed by repair and remodeling. The tenocytes control the healing process and manufacture new collagen to undergo remodeling. Unfortunately, healed tendons do not regain their full pre-morbid mechanical properties.

Muscle, tendon and ligament inflammation after injury is a complex process involving overlapping cell types and a cascade of molecules, including cytokines, permeability factors, prostaglandins, tumor necrosis factor and growth factors, among many others. Musculoskeletal inflammation is a visible expression of the highly complex innate immune mechanism of multiple cell types and hundreds of molecules choreographed to protect the body from injury and direct the healing response.

In the acute phase of inflammation, platelets bind to collagen, ultimately forming a platelet “plug.” They also secrete reparative mediators, such as TGF beta, which ultimately causes fibroblast proliferation and matrix secretion. Another important inflammatory mediator is IL1, which induces matrix metalloproteinase (MMP) secretion from fibroblasts. MMP degrades the damaged matrix and allows for inflammatory cell proliferation. Neutrophils destroy damaged tissue then undergo apoptosis, later undergoing phagocytosis by macrophages.

After 24 hours, macrophages and monocytes predominate. Macrophages secrete over 100 information molecules, predominantly pro-inflammatory mediators. By 14 days, the “granulation” phase becomes active, and lymphocytes predominate, supporting angiogenesis and collagen secretion. (A weakened lymphocyte response delays and inhibits adequate wound healing.)

The later stage of healing also involves proliferation and activation of fibroblasts that migrate into fibrin clot located in areas of blood extravasation in sites of inflammation. The fibroblasts secrete a hyaluronan-rich matrix and evolve into contractile myofibroblasts. New collagen fibers are organized into tendons and ligaments. The collagen fibers wind around each other and contract, expressing fluid and ultimately shortening to create a mechanically sound tendon or ligament.

During this process, vascular endothelium, mast cells and peripheral nerve cells also play a role in both the inflammatory and healing process. Improper healing can occur with an excessive inflammatory response and exuberant edema, making tendons or ligaments elongated or disorganized.

A fundamental difference in the use of herbs vs. pharmaceuticals is the multiplicity of effects of herbs due to their myriad constituents. Herbal constituents--such as terpenoids, alkaloids, polyphenols and glycosides--act on numerous receptors in the body with an “ensemble” effect. Most herbs contain many classes of constituents, thereby interrupting pathogenic mechanisms in multiple ways. This herbal complexity is similar to the complexity of inflammation in musculoskeletal conditions.

The following supplements have experimental and clinical evidence for benefit in musculoskeletal conditions. For a definitive review, I refer the reader to a recent article from the University of Pittsburgh on the use of natural anti-inflammatory agents in athletic injuries.[6]

Curcumin

Curcumin is a good example of the “ensemble effect” of an herb. The yellow pigment in the spice turmeric, curcumin has a long history of use in Ayurvedic medicine, including topically, orally and by inhalation. PubMed contains many articles in peer-reviewed journals on the clinical application of curcumin for inflammatory disorders. It has been used for disorders of skin and lungs, gastrointestinal disorders, wounds and sprains. Laboratory studies suggest antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal and anticancer effects.[7]

Curcumin down-regulates inflammatory transcription factors, enzymes and cytokines. As intimated above, all these molecules play an interdependent role in inflammation. This complex action contrasts with the singular mechanism of COX inhibition by NSAIDs and the blockade of tumor necrosis factors by TNF inhibitors. Curcumin generates its potency through its multiplicity of effects.

A double-blind study using a combination of curcumin and boswellia (an anti-inflammatory gum resin) showed significant improvement in 49 patients with osteoarthritis of the knee.[8] Curcumin has also been the subject of positive clinical studies in rheumatoid arthritis, chronic anterior uveitis and inflammatory orbital pseudotumor. The side effects of curcumin are minimal, but it can cause stomach upset.

Bromelain

Bromelain is a proteolytic enzyme extracted from the stem of the pineapple plant. Systemic enzyme therapy has a long history of use, particularly in Europe. Proteases like bromelain clear injured tissues of inflammatory cytokines, damaged peptides and proteins, and advanced glycation end products. In particular, bromelain appears to lower pro-inflammatory prostaglandins and promote the prostaglandin E1 pathway. Bromelain may retard the movement of neutrophils to sites of acute inflammation, degrade fibrin and fibrinogen, and lower kinin levels, thereby decreasing vascular permeability through a second pathway to the prostaglandin pathway. It may also lower pro-inflammatory cytokines.

Like curcumin, this ensemble of effects is a good match for the complex mechanisms of inflammation. Bromelain appears to be clinically effective in studies on wound healing and osteoarthritis.[9,10] The mechanistic overlap between these conditions and acute sprains and strains suggests its use in this setting as well. Bromelain can aggravate digestive ulcers and esophagitis and is a mild anticoagulant.

Lyprinol

This stabilized lipid extract of the New Zealand green-lipped mussel shows significant anti-inflammatory effects. Clinical studies of lyprinol have demonstrated it efficacy in treating osteoarthritis, rheumatoid arthritis and asthma.[11-13] An interesting study out of Australia showed that lyprinol was comparable in efficacy to ibuprofen and naproxen in an animal model without GI side effects.[14] Overall, the properties of lyprinol recommend its use in acute and chronic musculoskeletal conditions, without significant side effects.

Space permits only mention of other potentially beneficial natural compounds for acute and chronic musculoskeletal conditions. These include white willow bark (the source of acetylsalicylic acid), pycnogenol (derived from the bark of the maritime pine tree), boswellia (a resin from the Boswellia tree) and cat’s claw (a Peruvian herb).

Several nutrients are recommended for athletes to prophylactically reduce the effect of injuries. Most beneficial are omega 3 fatty acids and green tea polyphenols. Both have multiple anti-inflammatory properties and are protective against the oxidative-inflammatory effects of aging. A high quality fish oil (the most common source of omega 3 fatty acids) should state that it has been assayed and is free of heavy metals and halogenated hydrocarbons.

Dr. Kurn, a neurologist and acupuncturist, is the co-owner of Farmacopia, an herbal pharmacy in Santa Rosa.

Email: sidneykurn@comcast.net

References

1. Cunningham L, Kelsey J, “Epidemiology of musculoskeletal impairments and associated disability,” Am J Pub Health, 74:574-579 (1984).

2. Hootman JM ,et al, “Epidemiology of musculoskeletal injuries among sedentary and physically active adults,” Med Sci Sports Exer, 34:838-844 (2002).

3. Cryer B, “NSAID-associated deaths,” Am J Gastro, 100:1694-95 (2005).

4. Shield MJ, “Anti-inflammatory drugs and their effects on cartilage synthesis and renal function,” Eur J Rheum Inflamm, 13:7-16 (1993).

5. Leadbetter WB, “Anti-inflammatory therapy in sports injury,” Clin Sports Med, 14:353-410 (1995).

6. Maroon JC, et al, “Natural anti-inflammatory agents for pain relief in athletes,” Neurosurg Focus, 21:E11 (2006).

7. Aggarwal BB, et al, “Curcumin: the Indian solid gold,” Adv Exp Med Biol, 595:1-75 (2007).

8. Badria FA, et al, “Boswellia-curcumin preparation for treating knee osteoarthritis,” Alt Comp Ther, 8:341-348 (2004)

9. Brown SA, et al, “Oral nutritional supplementation accelerates skin wound healing,” Plast Recon Surg, 114:237-244 (2004).

10. Brien S, et al, “Bromelain as a treatment for osteoarthritis,” Evid Based Comp Alt Med, 1:251-257 (2004).

11. Brien S, et al, “Systematic review of the nutritional supplement Perna canaliculus in the treatment of osteoarthritis,” QJM, 101:167-179 (2008).

12. Gibson SLM, Gibson RG, “Treatment of arthritis with a lipid extract of Perna canaliculus,” Comp Ther Med, 6:122-126 (1998).

13. Emelyanov A, et al, “Treatment of asthma with lipid extract of New Zealand green-lipped mussel,” Eur Resp J, 20:596-600 (2002).

14. Whitehouse MW, et al, “Anti-inflammatory activity of a lipid fraction (Lyprinol) form the NZ green-lipped mussel,” Inflammopharmacology, 5:237-246 (1997).

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