Topical NSAIDs in the treatment of osteoarthritis pain

Osteoarthritis pain is one of the more frustrating problems we primary care clinicians have to manage. It is a ubiquitous problem. It is a bothersome complaint. And treatment options are not great. NSAID’s can provide some relief, but the operative word in that concept is some. And many people in the OA age group have GI issues or mild renal insufficiency which make NSAIDs problematic. Acetaminophen probably has equianalgesic effect with NSAIDs, but dosing needs to be limited to avoid hepatic problems. What about narcotics? Well, that class of medication certainly can help relieve pain in the short run, but they often place a patient on a slippery slope leading to tolerance, higher doses, and even more pain. So, narcotics should be avoided as much as possible for treatment of OA pain.

Another treatment option is topical non-steroidal gels, several of which are available, both prescription (e.g. Flector) and non-prescription (e.g. Aspercreme). Some patients feel these agents really help relieve their arthritis pain. They rub the gel onto their painful joints and the pain starts to diminish. The question this scenario raises is how is the medication working? Is the topical NSAID proving effective by diffusing through the skin, subcutaneous tissue, muscles, joint capsule, and synovial fluid, to directly reach the cartilage and bone areas which are generating pain?. Or is the medicine working because it is being absorbed into the blood stream, yielding a systemic effect? Or is it primarily a placebo effect leading to reduced pain?

A recent study in The Journal of Rheumatology suggests the third reason is most probable, that any reduction is pain is due to the placebo effect. In the October 2013 issue, a double-blinded randomized study was reported in which 555 individuals with OA pain were treated with either ketoprofen gel or placebo gel. Both groups experienced significant improvements in their pain. Notably, those treated with the placebo gel had greater pain reduction than those treated with the NSAID-containing gel.

The results of this study are illuminating, since they support what would appear to be the most rational and scientific understanding of how topical NSAIDs could exert a beneficial effect. It is unlikely that topical NSAIDs could diffuse through so many tissue layers to reach their intended target with a therapeutic concentration level. It is also improbable there would be enough absorption into the blood stream to yield a systemic effect, and if that is the mechanism of action, why not just take the medication orally? The fact that the placebo gel was even more effective than the NSAID-containing gel points more to the powerful effect the brain plays in modulating pain than to the pharmacologic effect of topical NSAIDs.

I am not one to discount making use of the placebo effect in appropriate situations. It is certainly safer to treat OA pain with a topical gel (whatever that gel contains) than with chronic narcotics, and if such gels lead to a perception of improved pain, so be it. But as scientists, we need to understand reality and have our medical practice guided by reason as much as possible. Sometimes an open and direct discussion with patients on the possible mechanisms of action of using NSAIDs topically versus taking them orally can promote a better acceptance of how to approach, work with, and live with OA pain.

Finally, though, I do draw the line on some creative topical creams compounded with a kitchen sink mixture of various medications. Quite a number of these nostrums are being produced by various compounding pharmacies, and they can include drugs such as an NSAID, baclofen, cyclobenzaprine, ketamine, lidocaine, etc. These bizarre topical combinations cannot possibly work pharmacologically to treat musculoskeletal or neuropathic pain. Their mechanism of action is clearly placebo generated. These creams are often provided “free” by the compounding pharmacy for the first month, a clever inducement to get physicians to prescribe them. Subsequent jars often cost thousands of dollars each. In my view, that use of the placebo effect is far too costly.

Richard Fleming, MD

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