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Natural anti-inflammatory agents for pain relief

Review

Joseph C. Maroon, Jeffrey W. Bost,* and Adara Maroon1Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA1Vanderbilt University, Nashville, TN, USA
Joseph C. Maroon: ude.cmpu@cjnooram; Jeffrey W. Bost: ude.cmpu@jtsob; Adara Maroon:
gro.yelkciwes@noorama*Corresponding authorReceived October 20, 2010; Accepted October 22, 2010.Copyright © 2010 Maroon JC

The use of both over-the-counter and prescription nonsteroidal medications is frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medications for chronic and degenerative pain conditions.

Although nonsteroidal medications can be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatment for pain relief, especially for long-term use.

Introduction

Pain, heat, redness, and swelling (dolor, calor, rubor, tumor) are the classic manifestations of the inflammatory process. Abnormalities of the joints of the spine, associated muscles, tendons, ligaments and bone structural abnormalities can all result in pain and need for neurosurgical consultations.

Typically, patients will not require immediate surgical intervention, and therefore require treatments to reduce pain and enhance quality of life activities.

In most cases, the genesis of pain is inflammatory, regardless of the etiology.

With the elucidation of the role of inflammatory cytokines, there is now a clear understanding of the pathways by which many anti-inflammatory drugs can alleviate inflammation and relieve pain.

The use of non-steroidal anti-inflammatory drug (NSAID) medication is still the mainstay of most classically taught clinicians for joint and spine related inflammatory pain, despite their commonly known side effects . NSAID mechanisms are primarily through interaction with proinflammatory cytokines interleukin (IL)-1a, IL-1b, IL-6 and tumor necrosis factor (TNF-α). Increased concentrations of TNF-α are believed to cause the cardinal signs of inflammation to occur.These proinflammatory cytokines result in chemoattractant for neutrophils and help them to stick to the endothelial cells for migration. They also stimulate white cell phagocytosis and the production of inflammatory lipid prostaglandin E2 (PGE2).

NSAIDs’ ability to interfere with the production of prostaglandin during the inflammatory cascade is the major mechanism cited for the anti-inflammatory success of these medications [Figure 1].

Figure 1

Schematic showing that when a cell membrane is injured the arachidonic acid pathway is activated to initiate the local inflammatory response through the production of prostaglandins, thromboxanes, and leukotrienes. Their activation requires the enzymes COX and LOX. The NSAIDs can block COX action and thereby prevent the formation of the COX-derived inflammatory mediators. 5-HPETE = 5-hydroperoxyeicosatetraenoic acid; LTC4 = leukotriene C4; PGE2 = prostaglandin E2; PGF2 = prostaglandin F2; PGI2 = prostacyclin; TXA2 = thromboxane.

Examples of natural anti-inflammatory

Plant- and animal-derived nutraceutical preparations have been used for hundreds and even thousands of years to obtain effective pain relief. Herbal medications are becoming increasingly popular because of their relatively few side effects. Nevertheless, there are problems associated with these dietary supplements, and their use requires knowledge of their biological action, clinical studies (both affirmative and negative), and potential interactions with other nutraceutical products and prescription medications.

The evaluation of nutraceutical preparations with appropriately designed controlled studies has exploded in recent years. There is now a greater degree of confidence based on controlled study design and improved quality of the investigators that has strengthened positive findings found using natural compounds to treat diseases. It is important for healthcare practitioners to learn about these scientific studies to counsel patients who are taking various dietary supplements, herbs minerals and vitamins for both disease treatment and prevention.

Quality considerations

The processes used to prepare herb-derived compounds pose complications when it comes to determining the quantity and concentration of the products. The preparation processes are not standardized, and therefore, the extraction process and the type of plant used may affect the true concentration of the product. In addition, there is a lack of uniformity within and between manufacturers. Although dietary supplements are not held to the same rigorous testing and standards as pharmaceutically derived medications in the US, there are many regulations that still control their manufacture because these are food products.

Omega-3 EFAs (fish oil)

The use of fish oil (in the form of cod liver oil), an omega-3 EFA, for the treatment of muscular, skeletal, and discogenic diseases, can be traced back to the late 18th century as detailed by Curtis et al., Unfortunately, because of the rapid onset of rancidity of this polyunsaturated oil when exposed to air, and hence its disconcerting odor, cod liver oil fell out of favor. With improved extraction techniques, such as using a protective nitrogen blanket and enhanced oxygen-free encapsulation methods, there is less chance of oxidation during the manufacturing process. The therapeutic benefits of fish oil can now be realized without the regurgitation and odor of previous products caused by peroxides and rancid tasting fish oil.

White willow bark

Bark from the white willow tree is one of the oldest herbal remedies for pain and inflammation, dating back to ancient Egyptian, Roman, Greek, and Indian civilizations, as an analgesic and antipyretic agent. Because of the gastric side effects of aspirin, there has been a resurgence in the use of white willow bark for the treatment of inflammatory syndromes. The mechanism of action of white willow bark is similar to that of aspirin which is a nonselective inhibitor of COX-1 and COX-2, used to block inflammatory prostaglandins.

Curcumin (turmeric)

Curcumin is a naturally occurring yellow pigment derived from turmeric (Curcuma longa), a flowering plant of the ginger family. It has traditionally been used as a coloring and flavoring spice in food products. Curcumin has long been used in both Ayurvedic and Chinese medicinesas an anti-inflammatory agent, a treatment for digestive disorders, and to enhance wound healing. Several clinical trials have demonstrated curcumin’s antioxidant, anti-inflammatory, and antineoplastic effects. Results of a study by Zandi and Karin suggested that curcumin might be efficacious in the treatment of cystic fibrosis because of its anti-inflammatory effect. Curcumin is known to inhibit inflammation by suppressing NF-kB, restricting various activators of NF-kB as well as stemming its expression.

Green tea

Green tea has long been recognized to have cardiovascular and cancer preventative characteristics due to its antioxidant properties. Its use in the treatment of arthritic disease as an anti-inflammatory agent has been recognized more recently. The constituents of green tea are polyphenolic compounds called catechins, and epigallocatechin-3 galate is the most abundant catechin in green tea.

Pycnogenol (maritime pine bark)

Pycnogenol, like white willow bark, is a nutraceutical material that has been used since ancient times. Pycnogenol is derived from the bark of the maritime pine tree (Pinus maritima) and hasbeen used for more than 2000 years. It has been considered helpful for wound healing, treating scurvy, healing of ulcers, and reducing vascular inflammation. It contains a potent blend of active polyphenols, which includes catechin, taxifolin, procyanidins, and phenolic acids. It is one of the most potent antioxidant compounds currently known.

Boswellia serrata resin (Frankincense)

The Boswellia species are trees located in India, Ethiopia, Somalia, and the Arabian Peninsula, and they produce a gum resin called olibanum, better known in the western world as frankincense. This resin possesses anti-inflammatory, anti-arthritic, and analgesic properties. Boswellia can inhibit the leukotriene biosynthesis in neutrophilic granulocytes by inhibiting 5-LOX, thus affecting various inflammatory diseases that are perpetuated by leukotrienes. Clinically, the substance is used in the treatment of degenerative and inflammatory joint disorders. It reduces the total white blood cell count in joint fluid, and it also inhibits leukocyte elastase, which is released in rheumatoid arthritis. In one recent study, a statistically significant improvement in arthritis of the knee was shown after 8 weeks of treatment with 333 mg B. serrata extract taken three times a day. The treatment improved function, but radiographically there was no change in the affected joints.

Resveratrol

Resveratrol is a plant-based polyphenol molecule that is found in various concentrations of many different plant sources. The plant is called Japanese Knot weed or Polygonum cuspidatum, andthe skins of red wine grapes are believe to have the most concentrated amounts of resveratrol. In plants, resveratrol is generally found in the plant skin and acts as a phytoalexin to protect the plant from infection, excessive UV radiation and aide in general plant defense. Resveratrol has also been found to have significant anti-mutation, anti-inflammatory, antoxidant and DNA protective actions, when consumed by animals and humans.

Uncaria tomentosa (cat’s claw)

Uncaria tomentosa and Uncaria guianensis are Peruvian herbs derived from woody vines with small claw-like thorns (hence the vernacular name, cat’s claw) at the base of the leaf, which allow the plant to climb to heights of up to 100 ft. Traditionally, the bark of cat’s claw is used to treat arthritis, bursitis, and intestinal disorders. The active ingredients appear to be polyphenols (flavonoids, proanthocyanidins, and tannins), alkaloids, and sterols. Various studies indicate that this Peruvian herb induces a generalized reduction in proinflammatory mediators.

Capsaicin (chili pepper)

Capsicum annum is a small spreading shrub which was originally cultivated in the tropical regions of the Americas but is now grown throughout the world, including the US. The small red fruit commonly used to accentuate chili owes its stinging pungency to the chemical, capsaicin.

This was isolated by chemists more than a century ago and constitutes approximately 12% of the chili pepper. This fruit has been used for various medicinal purposes by the native peoples of the American tropics for hundreds of years.

CONCLUSIONS

The human body’s natural response to injury results in inflammation-induced pain, swelling, and erythema. In order to reduce pain, anti-inflammatory agents such as NSAIDs act on the multiple inflammatory pathways, which, although often very effective, can have undesirable side effects such as gastric ulceration and, infrequently, myocardial infarction and stroke.
For centuries, natural anti-inflammatory compounds have been used to mediate the inflammatory process and often with fewer side effects. We have briefly reviewed several of the most commonly used plant- and animal-derived natural compounds that may possess similar effectiveness in treating the inflammatory reaction seen in both chronic and sub-acute pain syndromes encountered in a typical neurosurgical practice. Ongoing experiments and clinical trials should be continued to guide and provide their scientifically based effectiveness to reduce inflammation and promote wellness.

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