John Davis

Written by John Davis

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Are Nitroglycerin Patches an Effective Treatment for Overuse Injuries?

The next frontier in treatments for overuse injuries is in what you might call “biological treatments.”  Long dreamed about by doctors and runners alike, a pill, cream, or injection of a medication that would quickly and reliably boost your recovery from an overuse injury would be a major game-changer for injured runners.

Realistically, a silver bullet isn’t likely anytime soon.  But it is very possible that some innovative medications that are currently being researched will have a substantial positive effect on overuse injuries—of course, some will certainly turn out to be overhyped duds, too.

On that note, this week we’ll be looking at nitroglycerin patches, a promising emerging treatment for tendonitis, and examining if the current research supports their effectiveness.

Nitroglycerin in lab tests

Though most often associated with its use as an explosive, nitroglycerin (often termed “glyceryl trinitrate” to avoid alarming people) has a storied history in medicine as well.

It is commonly used to treat chest pain associated with heart disease, since it is a potent vasodilator: once metabolized, nitroglycerin is converted into nitric acid, which relaxes blood vessels and increases bloodflow.  Until relatively recently, though, nitroglycerin was never considered for treating overuse injury.

Tendon healing through nitric oxide on animal subjects

But animal research on the biological basis of tendon injury revealed that nitric oxide—the molecule formed when nitroglycerin is metabolized by your body—plays a significant role in tendon healing.

Though nitric oxide is found only sparingly in healthy tendon tissue, its production is ramped up significantly following an injury either an acute tendon injury, like a rupture, or an overuse injury like tendonitis.

Innovative research by Ali Bokhari and George Murrell at the University of New South Wales in Australia has demonstrated that, when rats with tendon injuries are fed a drug which inhibits nitric oxide production, their tendons heal worse than rats healing naturally.  And when injured rats are fed a drug that increases nitric oxide production, their tendons heal stronger and better-organized than rats who are not.

Nitroglycerin patches on humans

Further, the role of nitric oxide in tendon injury extends to humans as well.  Bokhari and Murrell evaluated samples of torn rotator cuff tendons that were to be discarded following surgical repair and found that nitric oxide was very common in these injured tendons too.  Of course, all of the rat experiments can’t be repeated in humans, because it’d be pretty unethical to intentionally inhibit recovery, and the drugs which Bokhari and Murrell used to supply nitric oxide to their rats probably aren’t tested for use in humans yet.  Fortunately though, there is a reasonably safe drug which can supply nitric oxide to your body: nitroglycerin.

Bokhari and Murrell instigated human trials using nitroglycerin patches to deliver nitric oxide to injured tendons.  The patches were ideal because they can be positioned over the most painful area of the tendon, and because they deliver a continuous amount of the drug throughout the course of a day.

Bokhari and Murrell tested nitroglycerin patches as a supplemental treatment to normal physical therapy for lateral epicondylitis (tennis elbow), supraspinatus tendinopathy (shoulder tendonitis), and Achilles tendonitis over a period of six months.  All three trials used control groups with placebo patches, and all three found significant benefits several weeks after the patients began to use the nitroglycerin patches.

Results a few years out were varied; the Achilles tendonitis patients who had used the nitroglycerin patches for six months continued to be better off than the placebo group at three years out, but there were no differences between the lateral epicondylitis groups five years out.

What further studies reveal

Though Bokhari and Murrell’s work is promising, the support for nitroglycerin patches is not universal.  Three researchers in the UK conducted an experiment with Achilles tendonitis patients similar to Bokhari and Murrell, but did not find any additional benefit when nitroglycerin patches were added to a standard rehab program. And among the patients who went on to have surgery, the tendon fragments debrided during surgical repair showed no effects consistent with a higher supply of nitric oxide.

This might be simply because the treatment doesn’t work, but it could also be a failure of the delivery mechanism.  Since nitroglycerin readily produces nitric oxide inside the body, the lack of its presence in the tendon samples harvested during surgery might indicate that the patches aren’t doing their job.

Indeed, Bokhari and Murrell tested a specially-formulated nitroglycerin patch designed to treat tendon problems—they had previously been cutting quarter-sections out of nitroglycerin patches for chest pain to control the dosage—but found barely any benefit with the new patch compared to a placebo patch.

So, are nitroglycerin patches effective?

The questions surrounding whether nitroglycerin is truly beneficial and how to properly deliver it are still unanswered, but this has not stopped one review study by researchers at the University of Santo Tomas Hospital the Philippines from endorsing nitroglycerin patches as a good adjunctive treatment for tendonitis in addition to a standard physical therapy rehab program.

Nevertheless, more work needs to be done to uncover how nitroglycerin might help in recovery.  Is it a true biological effect on the tendon, or does it simply have a pain-dulling effect by increasing bloodflow, much like heating up a stiff tendon reduces pain?

There is still a good bit of research that needs to be done before nitroglycerin patches are considered anything more than an experimental, off-label use of medication for chest pain.  But it’s an emerging treatment that’s shown good promise, both in human trials and in basic biological investigations.  With more research, it may become a viable or even routine treatment for some of the common tendon ailments that afflict runners like Achilles tendonitis and patellar tendonitis.

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References

1. Bokhari, A. R.; Murrell, G. A. C., The role of nitric oxide in tendon healing. Journal of Shoulder and Elbow Surgery 2012, 21 (2), 238-244.
2. Kane, T. P. C.; Ismail, M.; Calder, J. D. F., Topical Glyceryl Trinitrate and Noninsertional Achilles Tendinopathy A Clinical and Cellular Investigation. American Journal of Sports Medicine 2008, 36 (6), 1160-1163.
3. Gambito, E. D.; Gonzales-Suarez, C. B.; Oguiñena, T. I.; Agbayani, R. B., Evidence on the Effectiveness of Topical Nitroglycerin in the Treatment of Tendinopathies: A Systematic Review and Meta-Analysis. Archives of Physical Medicine and Rehabilitation 2010, 91 (8), 1291-1305.

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