Wednesday, August 16, 2006

The Truth about NSAIDs, Ice, and other anti-inflammatories

For some of us, popping an aspirin is as common as brushing our teeth. But what are we really doing to our bodies when we treat an ache or a pain with some ibuprofen or break out the ice pack?

I've learned a lot about inflammation in the last few months since I joined the Immunology Department as a postdoc. In addition, our lab studies the connection between inflammation and atherosclerosis (accumulation of plaques in the arteries). Contrary to traditional belief, atherosclerosis is more than just a metabolic disease. It is also a chronic inflammatory disease, similar to arthritis or asthma. But I digress...

First off, what are NSAIDs? They are non-steroidal anti-inflammatory drugs, including aspirin (salicylate), Ibuprofen (Motrin, Advil, etc.), acetaminophen (Tylenol), and COX-2 specific inhibitors, such as Vioxx or Celebrex. Although they all act on the same pathway, each drug has slightly different effects for unclear reasons.

Efficacy of Different NSAIDs:
For instance, in addition to pain-relieving, anti-inflammatory properties, aspirin is also the most potent at preventing clotting, which is why patients are advised not to take it before a surgery. In addition, people suffering from symptoms of a heart attack have been advised to take an aspiring while waiting for the ambulance. The reasoning behind this suggestion is that if the heart attack is being induced by a clot, the aspirin will thin the blood and potentially break up the clot. Acetaminophen is least effective in anti-inflammatory properties but is still effective as an anti-pyrogenic (preventing fever). In addition, acetaminophin is renowned for being gentle on the tummy. Ibuprofen is typically most effective in relieving aches and pains associated with soft tissue injuries and joint pain (overuse injuries from training).

How do NSAIDs work?
Invariably, all these drugs block pain by inhibiting the enzyme COX-2 (cyclooxygenase-2). This enzyme converts arachidonic acid (a type of fatty acid) into prostaglandins. There are several different types of prostaglandins, all of which have important functions in various pathways, such as stimulating cell growth, inhibiting cell death, stimulating the growth of new blood vessels (angiogenesis), recruitment of platelets (clotting), pain, swelling, and inflammation. Because COX-2 is involved in tissue repair and wound healing, studies have been done to investigate whether inhibition of COX-2 activity with NSAIDs might delay healing.

Sidenote--NSAIDs and fever:

Prostaglandins act in many different tissues of the body, including the hypothalamus of the brain, which is where prostaglandins go when they want to signal the brain to induce a fever. That's why we also take NSAIDs when we're sick to reduce a fever. You may have heard the old wive's tale, "Feed a cold, starve a fever," which advocates letting the patient "sweat it out" to allow the immune system to do its thing. Although, the body induces fever when we're sick as an attempt to kill off invading microbes by "nuking" them, the body's own cells don't fare too well if the fever is too high or persists for too long. Our cells may be able to withstand the increased temps better than the bugs but not for long. That's why it's better to control the fever with NSAIDs when you're sick right away. It's better to be safe and make yourself comfortable (and drink lots of fluids!). If the fever doesn't go down or returns when the NSAIDs wear off for more than 24 hours, see a doctor right away to see if you need antibiotics.

"For the most common disorders associated with fever, however, there's no convincing evidence that fever itself hastens recovery from common infections or that it correlates with a better outcome. There's experimental evidence that higher temperatures are harmful to certain bacteria, but medical experts disagree about whether this translates into a role for fever improving our ability to fight infection. In fact, most experts do agree that suppressing fever (for example, with acetaminophen) is not harmful, may be helpful, and they would never suggest trying to raise body temperature when fever is present...Since higher body temperature doesn't contribute to recovery, efforts to raise body temperature during a fever aren't advisable and may even be dangerous. And while one's appetite may be poor when a fever accompanies illness, there's no clear benefit (and there may be harm) to the strategy of trying to "starve a fever.""
--Robert H. Shmerling, M.D. 2001

Sidenote--Side-effects NSAIDs (COX-1):
Unfortunately, except for the COX-2-specific inhibitors, the other NSAIDs also block COX-1, a closely-related enzyme to COX-1. COX-1 is responsible for making prostaglandins which ultimately results in maintenance of the mucosal lining of the gut. So if COX-1 is inhibited on a chronic basis (e.g. one who pops Advil 2-3x/day), this lining can be worn down, leading to gastric problems including ulcers. (The COX-2 specific inhibitors were designed for people who have chronic pain, such as arthritis, and need to use COX-2 inhibitors on a daily basis, but have sensitive stomachs). COX-1 also stimulates production of a prostaglandin involved in clotting within the bloodstream, which can contribute to heart attack and stroke, especially if individuals are already suffering from atherosclerosis. Inhibiting COX-1 with aspirin, in these instances, can actually help prevent these conditions in afflicted individuals (see my digression on aspirin, above).

NSAIDs and Muscle Injuries:
Why am I going into all this? The question of whether to use anti-inflammatories to "treat" overuse injuries has become a popular debate. First, anti-inflammatories will not "treat" or heal an overuse injury. They will reduce swelling and pain. If you've gotten in the habit of popping an Advil to mask the pain of your IT band while you go out for your daily 10 mile run, you may be doing more harm than good. Pain is your body's way of telling you there's something wrong. You need to address it by going to a good sports medicine doc, physcial therapist, or other highly qualified sports health professional, who can evaluate your biomechanics and conformation and put you on a program in which you can allow the injury to heal and then prevent it from happening again. Many people have turned a minor sprain into a tendon rupture from abusing NSAIDs, ignoring the pain, and continuing to run without addressing the underlying problem.
This said, taking an Advil to make yourself more comfortable and relieve pain induced by an injury is perfectly fine, even advisable, and will not delay the healing process. As long as you are taking other measures to allow yourself to heal (e.g. rest, ice, compression, elevation (RICE)), the occasional use of NSAIDs to minimize pain from an injury will not delay healing.

In addition, if you have chronic inflammatory condition, like arthritis or tendonitis, the use of NSAIDs may actually be beneficial. In this instance, your body's immune system has tried (and failed; hey, we're not perfect!) to heal the injury but is now in a vicious, futile cycle of a chronic inflammatory state, which can actually weaken your body overall. The immune system can't be as good as a sentinel at warding off infection when its investing so much energy in inflammation for a chronic injury that's never going to heal.
Proper use of NSAIDs can might actually help speed recovery. The reasoning is that when we're in less pain, we're more comfortable so we are more relaxed and sleep better, thus speeding the healing process. In addition, recent research has found gentle movement of the injured limb may help speed recovery by increasing blood flow to the area and also preventing muscle atrophy (thus R.I.C.E. has now become M.I.C.E., in which the "rest" has been replaced with "move (gently)).
Ice and Injury:

Along similar lines, use of ice to reduce inflammation directly over the injured area, is also an effective measure of minimizing pain, reducing inflammation, and perhaps preventing onset of muscle trauma, soreness, and injury. Many Olympic and pro athletes, such as Olympic marathoners, Paula Radcliffe and Deena Kastor, swear by "ice baths" and actually lower their entire body into a literal bath of ice after a hard workout. Now that's hard-core! Cold reduces swelling and initially restricts blood flow, providing a natural compress on the microscopic tears in the tissue that are leaking blood into the traumatized area. Shortly, the body will recruit new blood to the cold area that flushes out metabolic wastes and lactic acid - byproducts of heavy muscle activity.

Other informative websites on NSAIDs:
Common Exercise Myths
OTC Pain Medication (Univ of Chicago)
NSAIDs and Musculoskeletal Treatment
NSAIDs and sports injury (Physioroom)
Ice Therapy websites:
Ice in Your Bath (Squashsite)
Research articles (NSAIDs and Treatment Injured Muscle):
1. Vignaud A, Cebrian J, Martelly I, Caruelle JP. Effect of anti-inflammatory and antioxidant drugs on the long-term repair of severely injured mouse skeletal muscle. 2005. Exp Physiol. 90(4):487-495.
2. Baldwin Lanier A. Use of nonsteroidal anti-inflammatory drugs following exercise-induced muscle injury. 2003. Sports Med. 33(3):177-185.
3. Dudley GA, Czerkawski J, Meinrod A, Gillis G, Baldwin A, Scarpone M. Efficacy of naproxen sodium for exercise-induced dysfunction muscle injury and soreness. 1997. Clin J Sports Med. 7(1):3-10.


bunnygirl said...

How do you feel about herbal anti-inflammatories, like turmeric?

As for ice baths, I've done them before, but I find them less of a shock to the system if you cool the water gradually. No point giving yourself a heart attack when all you want is to cool your legs.

stephanie said...

This is very interesting. Thank you for sharing it with the blogging community!

jessie_tri_mn said...

Good stuff! Thanks for sharing. You do interesting work. I've often wondered why acetaminophen and ibuprofen have different effects on me.

I was one of those who attempted to treat my overuse injuries with ibuprofen. I've since given this up. I figure if there is pain during a workout, I should probably know about it :)

Rachel said...

Bunnygirl--I think herbal anti-inflammatories basically work the same way as clinically approved drugs. Your body does process them slightly differently so every person will respond differently. However, it will ultimately target the same pathway.

Cliff said...


Thanks for the info. I never use anti-inflammatories. Only when I am very sick do I ever use aspirin. In fact, i haven't use it for this year.

I heard NSAIDs inhibit muscle recovery.

Ice baths all the i am not that hard core..i only ice my lower body.

Rachel said...

Cliff--I don't think NSAIDs inhibit muscle recovery unless they are overused.

IMmike said...

one of the md/phds I work with swears that I would be best served if I kept a steady stream of ibuprofen in my body at all times. He seems to think that the negative effects (liver damage) are overrated. I'm skeptical. Still, I use advil ALL THE TIME when I'm sore.

Britney said...

Thanks for the refresher course on NSAIDs (I did a presentation about them back in college, but that now seems like eons ago!). I am really loving being in the DPW lab and getting to know some of your buddies from there; I even got to party with Seth for his B-Day! Glad to hear you are feeling better!

trifrog said...

I posted a question about this on Cleveland Triathlon Club's forum as such:

"If inflammation is part of the body's response to injury in order to encourage healing, then we attempt to reduce/eliminate that inflammation with icing/heating/NSAIDs, what are we doing in regards to the healing part in favor of the comfort part?"

I re-phrase it after reading your post to say:

"If the inflammation is part of the healing process, how does reducing the inflammation not affect healing?"

Is it that the body over-does it and sends too many fluids to the area and we are seeking to reduce that swelling without eliminating it?

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