Rubbing It In For Pain Relief

When something like a knee hurts, there's a natural tendency to rub it. And if it really hurts, most of us will think about popping a pain-relieving pill of some kind—acetaminophen (Tylenol) for starters, or perhaps one of the nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin, ibuprofen (Advil, Motrin), or naproxen (Aleve, Naprosyn).

But there are also dozens of topical pain relievers—creams, ointments, and oils that let us rub and get our pain medication. The over-the-counter products are sometimes grouped into a "muscle rub" section at the drugstore. (The cortisone creams and other products for dealing with minor skin irritations are in a different section and aren't covered in this article.)

Applying medicine right to where it hurts certainly has a lot of intuitive appeal. And for people whose gastrointestinal tract doesn't react well to NSAIDs (a common problem), or who are reluctant to take pills for whatever reason, the topical approach is tempting.

The rub? Lingering doubts about whether these remedies work. And it can be hard to figure out whether a treatment is effective. The bar can be set pretty low: an ointment that provides a soothing sensation for a short while might be said to work by some definitions. And the placebo effect—benefit that comes from the patient's expectations rather than the treatment itself—is a major complicating factor in treatment of something as subjective as pain.

On the other hand, there's no question that active medicine can penetrate the skin and get into the body (how much is absorbed is a separate question). And, at least in theory, exposing just a painful area to a medication should mean fewer side effects than taking a pill, which involves gastrointestinal absorption and circulation of the drug in the blood.

Here's a quick rundown of some of the active ingredients in commonly available topical pain relievers:

NSAIDs

NSAID gels and ointments are not new, but they're getting a closer look these days. Rofecoxib (Vioxx) and other drugs in the COX-2 class had been positioned as safer, "gut-sparing" alternatives to the oral NSAIDs, but rofecoxib was pulled off the market in 2004, so there's now a gap that the topical NSAIDs might fill. (Celebrex, a different COX-2 inhibitor, is still on the market.) The FDA has approved a gel form of an NSAID called diclofenac (pronounced dye-KLOE-fen-ak) for osteoarthritis and there are diclofenac patches. Several ibuprofen creams are available.

The gastrointestinal problems (such as stomach upset, ulcers and bleeding) caused by oral NSAIDs are the result of both direct irritation of the gut's mucosal lining and systemic effects—chiefly the lowering of prostaglandin levels in the blood, which may reduce the integrity of the gastrointestinal lining. So if an NSAID delivered topically gets into the blood in large amounts and lowers prostaglandin levels, it might very well have a similar side-effect profile as one that has been swallowed—even in the absence of direct contact with gastrointestinal tissue. But from what has been seen so far, gels and ointments result in lower NSAID blood levels than the pill forms of the drugs. For example, the blood level from using topical diclofenac is about 6 percent of the level that results from the same dose of the drug in oral form.

The research is spotty, but those lower blood levels seem to translate into fewer side effects, aside from local skin irritation. In a study comparing an ibuprofen ointment to ibuprofen pills published in 2008 in the journal BMJ, people in the ointment group suffered fewer side effects than those who took pills.

Fewer side effects don't mean much if topical NSAIDs don't work to ease pain. Indeed, some experts look at the low blood levels and say that topical drugs can't be very effective in such low concentrations, aside from perhaps having some skin-deep, anti-inflammatory effect.

The data from clinical trials are mixed and open to multiple interpretations. A 2004 meta-analysis published in BMJ came to the conclusion that after the first two weeks of use, there was no evidence that topical NSAIDs were any more effective than a placebo. The Medical Letter, a well-regarded newsletter on new therapies, said the diclofenac gel might be modestly effective but also noted that the high placebo response leaves room for doubt. The ibuprofen pill and ointment study published in BMJ ended in a tie in terms of pain relief effectiveness, but researchers noted in their conclusion that one interpretation of the results could be that neither preparation is particularly effective.

The bottom line: NSAID ointments and gels probably are less likely to cause side effects than the oral versions, but there are doubts about how effective they are.