Say you're at the beach, and you get sand in your eyes. How do you know the sand is there? You obviously can't see it, but if you are a normal, healthy human, you can feel it, that sensation of extreme discomfort, also known as pain. Now, pain makes you do something, in this case, rinse your eyes until the sand is gone. And how do you know the sand is gone? Exactly. Because there's no more pain. There are people who don't feel pain. Now, that might sound cool, but it's not. If you can't feel pain, you could get hurt, or even hurt yourself and never know it. Pain is your body's early warning system. It protects you from the world around you, and from yourself. As we grow, we install pain detectors in most areas of our body. These detectors are specialized nerve cells called nociceptors that stretch from your spinal cord to your skin, your muscles, your joints, your teeth and some of your internal organs. Just like all nerve cells, they conduct electrical signals, sending information from wherever they're located back to your brain. But, unlike other nerve cells, nociceptors only fire if something happens that could cause or is causing damage. So, gently touch the tip of a needle. You'll feel the metal, and those are your regular nerve cells. But you won't feel any pain. Now, the harder you push against the needle, the closer you get to the nociceptor threshold. Push hard enough, and you'll cross that threshold and the nociceptors fire, telling your body to stop doing whatever you're doing. But the pain threshold isn't set in stone. Certain chemicals can tune nociceptors, lowering their threshold for pain. When cells are damaged, they and other nearby cells start producing these tuning chemicals like crazy, lowering the nociceptors' threshold to the point where just touch can cause pain. And this is where over-the-counter painkillers come in. Aspirin and ibuprofen block production of one class of these tuning chemicals, called prostaglandins. Let's take a look at how they do that. When cells are damaged, they release a chemical called arachidonic acid. And two enzymes called COX-1 and COX-2 convert this arachidonic acid into prostaglandin H2, which is then converted into a bunch of other chemicals that do a bunch of things, including raise your body temperature, cause inflammation and lower the pain threshold. Now, all enzymes have an active site. That's the place in the enzyme where the reaction happens. The active sites of COX-1 and COX-2 fit arachidonic acid very cozily. As you can see, there is no room to spare. Now, it's in this active site that aspirin and ibuprofen do their work. So, they work differently. Aspirin acts like a spine from a porcupine. It enters the active site and then breaks off, leaving half of itself in there, totally blocking that channel and making it impossible for the arachidonic acid to fit. This permanently deactivates COX-1 and COX-2. Ibuprofen, on the other hand, enters the active site, but doesn't break apart or change the enzyme. COX-1 and COX-2 are free to spit it out again, but for the time that that ibuprofen is in there, the enzyme can't bind arachidonic acid, and can't do its normal chemistry. But how do aspirin and ibuprofen know where the pain is? Well, they don't. Once the drugs are in your bloodstream, they are carried throughout your body, and they go to painful areas just the same as normal ones. So that's how aspirin and ibuprofen work. But there are other dimensions to pain. Neuropathic pain, for example, is pain caused by damage to our nervous system itself; there doesn't need to be any sort of outside stimulus. And scientists are discovering that the brain controls how we respond to pain signals. For example, how much pain you feel can depend on whether you're paying attention to the pain, or even your mood. Pain is an area of active research. If we can understand it better, maybe we can help people manage it better.
Recimo da ste na plaži, i upadne vam pijesak u oči. Kako znate da ondje ima pjeska? Očito ga ne možete vidjeti, ali ako ste normalno, zdravo ljudsko biće, osjetite ga, taj osjećaj ekstremne neugode, poznat i kao bol. Sad, bol vas može potaknuti na nešto, u ovom slučaju, da isperete oči dok pijeska ne bude. I kako znate da pijeska nema? Točno tako. Jer nema boli. Postoje ljudi koji ne osjećaju bol. Sad, to možda zvuči super, ali nije. Ako ne osjetite bol, možete se ozlijediti, ili ozlijediti sebe a da ne shvatite to. Bol je rani sustav upozorenja vašeg tijela. Štiti vas od svijeta oko vas, i vas samih. Kako rastemo, stvaramo detektore za bol u čitavom tijelu. Ovi detektori specijalizirane su moždane stanice nazvane nociceptori koji se protežu od vaše kralježnice do kože, mišića i zglobova, zuba i nekih nutarnjih organa. Baš kao i sve živčane stanice, one provode električne signale, šaljući informacije sa svoje lokacije natrag do mozga. Ali, za razliku od drugih živčanih stanica, nociceptori prorade ukoliko se događa nešto što što čini štetu. Dakle, nježno dotaknete vrh igle. Osjetit će te metal, i to su vaše regularne moždane stanice. Ali nećete osjećati nikakvu bol. Sad, što jače oslanjate prst na iglu, to ste bliži pragu nociceptora. Pritisnite dovoljno jako, i preći ćete taj prag i nociceptori se okidaju, govoreći vašem tijelu da prestane raditi to što radite. Ali taj prag nije čvrsto postavljen. Određene kemikalije prilagođuju nociceptore, smanjujući vaš prag na bol. Kada su stanice oštećene, one i druge obližnje stanice počinju proizvoditi te kemikalije kao lude, smanjujući prag nociceptora do točke gdje samo dodir može uzrokovati bol. I ovdje dolaze lijekovi protiv bolova bez recepta. Aspirin i ibuprofen blokiraju proizvodnju jedne vrste ovih kemikalija za prilagodbu, imena prostaglandini. Pogledajmo kako to čine. Kada su stanice oštećene, one otpuštaju arahidonsku kiselinu. I dva enzima COX-1 and COX-2 pretvaraju tu kiselinu u prostaglandin H2, koji se potom pretvara u hrpu drugih kemikalija koje rade hrpu stvari, uključujući podizanje temperature, stvaranje upale i smanjivanje praga za bol. Sad, svi enzimi imaju područje djelovanja. To je mjesto gdje se u enzimu događa reakcija. Područje djelovanja COX-1 i COX-" pristaju arahidoničkoj kiselini vrlo dobro. Kao što vidite, nema mjesta. Sad, na tom području aspirin i ibuprofen rade. Rade različito. Aspirin je kao hrpt dikobraza. Ulazi u područje djelovanja i odvaja se, ostavljajući pola sebe ondje, blokirajući taj prolaz i onemogučujući da se arahidonička kiselina smjesti. Ovo trajno deaktivira COX-1 i 2. Ibuprofen pak ulazi na područje djelovanja, ali se ne raspada ili mijenja enzim. COX-1 i 2 slobodni su ispljunuti ga van, ali za vrijeme dok je ibuprofen tamo, enzim ne može na sebe vezati arahidonsku kiselinu i ne može imati normalne reakcije. Ali kako aspirin i ibuprofen znaju gdje je bol? Pa, ne znaju. Kada su u vašem krvotoku, pronose se kroz tijelo, i idu na bolna područja kao i na normalna. Tako rade ibuprofen i aspirin. Ali postoje druge dimenzije boli. Neuropatska, na primjer, je bol koju stvara oštećenje živčanog sustava, nema potrebe za vanjskom stimulacijom. I znanstvenici su otkrili da mozak kontrolira kako reagiramo na signale boli. Na primjer, koliko boli možete osjećati ovisi o tome da li ste obratili pozornost na nju, ili čak vaše raspoloženje. Bol je područje aktivnog istraživanja. Ako ju bolje razumijemo, možda ćemo ju moći bolje kontrolirati.