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How does ibuprofen know where the pain is?

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Paging Dr. Internet, we need a diagnosis. In this series, Mashable examines the online world’s influence on our health and prescribes new ways forward.


When you twist open a bottle of Advil in search of relief from a pounding headache, nagging back pain, or ruthless cramps, do you ever stop and wonder how the small pills or capsules you consume actually work to take away your pain?

If you’re anything like me, the answer is no. You know Advil’s purpose, you take the recommended dose when needed, and you wait for it to do its thing — no mind-boggling questions asked. Every so often, however, Advil, Motrin, and other pain and fever reducers that contain ibuprofen, a non-steroidal anti-inflammatory drug, spark a sense of curiosity and inspire a simple yet complex question: “How does ibuprofen know where the pain is?”

Perhaps this is the first time you’ve personally considered the question, but it’s been circulating around social media for more than a decade. Alternative versions were tweeted in June 2011, but the earliest “How does ibuprofen know where the pain is?” tweet I could track was an old-school retweet posted by Twitter user Morgan Max (@antimrgn) in September 2011.

“At the time that I quoted this tweet, this had been something that I always thought about and wondered, but never tweeted about…This was the first time I had seen it online,” Max told Mashable in a Twitter DM. Though Max first saw the question tweeted in 2011, she said she’s seen various versions pop up in the past few months.

Since ibuprofen received a patent and was approved as a prescription in the 1960s, the true origin of “How does ibuprofen know where the pain is?” remains unknown. There’s a good chance people asked the question long before social media existed, but in the decade since Max’s retweet, “How does ibuprofen know where the pain is?” transformed into somewhat of a meme.

People keep tweeting the question, the tweets keep going viral, and responses are often split between people who think the thought is hilarious, those who know how the drug works and wonder how others could be so ignorant, and those who stop and earnestly wonder, “Huh! How does it know where the pain is?”

How does ibuprofen gain meme status?

The first time Katie Johantgen, an actor based in New York, saw a “How does ibuprofen know where the pain is?” tweet, she said she found it incredibly funny. But the novelty quickly wore off when she realized just how frequently people tweet the question.

“The first time I noticed it was actually kind of recently… definitely this past year. I remember the first time I saw it I laughed,” Johantgen explained in a phone call with Mashable. “Then I saw it again, and I think it was far enough apart that I wasn’t sure if I’d seen it before. So I click on the tweet and I’m reading the comments, and eventually I see someone being like, ‘Ugh, this tweet again,’ and I’m like, ‘Oh that’s right, I have seen this before.'”

When Johantgen saw the question tweeted a third time a few weeks later she’d had enough. Along with a screenshot of the viral post she tweeted, “Gonna tweet this tomorrow so I can go viral.” The following day she kept her bit going and tweeted, “How does ibuprofen know where the pain is LOL WHAT DO U GUYS THINK?! LIKE AND SUBSCRIBE!!!”

While the question regularly amasses tens of thousands of likes on Twitter, in 2021, it’s also drawn millions of views and likes on TikTok, along with attention from medical experts.

On July 25, 2021, 22-year-old TikTokker Liv Pearsall included the question in one of her videos titled, “Liv’s Questions About World – Part 2,” which features a collection of random ideas, such as, “Why don’t men wear dresses?” and “If airplanes are fast why do they feel slow?”

Pearsall said she’d definitely come across “How does ibuprofen know where the pain is?” before making the video, but she explained she wasn’t aware the question had reached meme status.

“That’s the thing: I wasn’t aware of it. I’d heard of it before — I feel like those are contradictory statements — but when I wrote it down to record my audio I wasn’t like, ‘Oh I’ll reference this popular meme that lots of people [use],” Pearsall said in a call. “I had definitely read it somewhere before, but I could not tell you where. It’s circulated so many places that I don’t really know where I first saw it.”

With more than five million views, Pearsall explained the “How does ibuprofen know where the pain is?” video is now her second most viewed TikTok. It’s even been stitched by a few medical experts on TikTok, including @drsood and @dr.noc, who each set out to accurately answer the common question.

“I didn’t realize that this had been an ongoing question for a decade, I just saw the video that I stitched from Liv and was like, ‘Oh, I very clearly know the answer to that question. I’ll just make a quick video,” Dr. Noc, a scientist in South Florida who researches and develops therapeutics for respiratory infectious diseases including COVID-19, shared in a phone call. For privacy reasons, he asked that we refer to him by his social media handle instead of his first and last name in this article.

In his reaction to Liv’s video (which is now his most viral TikTok at 9.4 million views) Dr. Noc gave one of the most simplistic ibuprofen explanations he could muster:

“How ibuprofen know where pain? Ibuprofen have secret. Ibuprofen not know where pain, ibuprofen everywhere. Whole body. Ibuprofen inhibit COX. No pain. Only notice where pain. Science.”

For those who still don’t quite get how the drug works or are eager to learn more, have no fear. Dr. Noc further described ibuprofen’s mechanism of action in our call.

OK, so how does ibuprofen know where the pain is?

“When you take ibuprofen, it goes into your stomach and then gets absorbed into the general blood supply throughout the body. From there, it diffuses and distributes out into all of your tissues, rather than accumulating in one particular region of your body that is in pain,” Dr. Noc explained.


“It diffuses and distributes out into all of your tissues, rather than accumulating in one particular region of your body that is in pain.”

“In the specific tissues where you are experiencing pain, some of your cells are turning arachidonic acid into prostaglandins, which cause inflammation and the sensations that you notice as pain,” he continued. “Ibuprofen works by preventing the production of those inflammation-signaling prostaglandin molecules, by inhibiting a type of enzyme called cyclooxygenase, or ‘COX.’ Ibuprofen’s role is preventing the production of the messenger molecules that lead to inflammation.”

Essentially, the drug disperses throughout your entire body. But you only feel pain relief in the places you had pain initially.

“…You are only going to notice the effects of ibuprofen in the tissues and muscles that were making lots of prostaglandins and causing pain and inflammation, even if there is also ibuprofen idly present in other parts of the body,” he said.

One thing Dr. Noc wanted to stress is that just because ibuprofen can make us laugh in this context doesn’t mean the drug should be viewed lightly. Like any over-the-counter medication, he says we should be cautious about how much and how often we take it, because it “can have some pretty bad toxicities to the stomach and intestines.”

The undying humor of repetitive ibuprofen tweets

Now that you understand how ibuprofen targets pain and inflammation, will you find the tweets a bit less funny? Possibly. But we have a feeling it’s one of those memes that will still be popping up on your timelines no matter how many times it’s explained.

Though some people, like Katie Johantgen, grow tired of seeing the same questions continually go viral on social media, it seems the internet isn’t ready to give up on “How does ibuprofen know where the pain is?” yet.

Why is the question still so funny more than a decade after it first appeared online? It’s likely a combination of legitimate curiosity, a love of simplistic humor, and a desire to unpack a somewhat complex topic.


“I think it’s just funny because it’s so dumb, but at the same time it’s a genuinely good question.”

“I think it is a genuine thing people wonder,” Johantgen said. “It’s sort of like, ‘Who shuts the door after the bus driver gets off the bus?’ It’s like those things you think of when you’re high, like ‘Why are pizza boxes square when a pizza is round?’ I think it’s just funny because it’s so dumb, but at the same time it’s a genuinely good question.”

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Even after learning ibuprofen’s mechanism of action, there’s still a joke to be made about the cyclooxygenase enzyme the drug inhibits, which, in case you forgot, is abbreviated COX.

“I think the top comment on my video is, ‘So you’re saying it’s a cox blocker?'” Dr. Noc explained after learning that similar jokes — which are clearly a play on the term cock blocker — appear in the replies of several viral “How does ibuprofen know where the pain is” tweets from the past decade. It’s a meme with several layers.

In Dr. Noc’s mind, the question and subsequent jokes — no matter the intention behind them — are hopefully leading to some deeper comprehension of ibuprofen and other drugs.

“You can go from not understanding anything about how ibuprofen works to having a pretty good understanding in the span of like 30 seconds,” he said. “So maybe there’s some value there.”

You hear that? Memes can make us laugh and teach us valuable life lessons.

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