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 pesak u oči. Kako znate da je pesak tamo? Jasno je da ga ne možete videti, ali ako ste normalno, zdravo ljudsko biće, možete ga osetiti, taj osećaj izuzetne neugode, takođe poznat i kao bol. Sada, bol vas tera da nešto uradite, u ovom slučaju, da ispirate oči dok ne uklonite pesak. A kako znate da peska više nema? Upravo. Zato što više nema bola. Postoje ljudi koji ne osećaju bol. E sad, to može zvučati super, ali nije. Ako ne osećate bol, možete se povrediti ili čak sami sebe ozlediti, a da to uopšte ne znate. Bol je sistem u telu za rano upozoravanje. On vas štiti od sveta koji vas okružuje, kao i od vas samih. Kako odrastamo, postavljamo detektore bola u većini delova našeg tela. Ovi detektori su specijalizovane nervne ćelije koje se zovu nociceptori, a koji se protežu od kičme do kože, mišića, zglobova, zuba i nekih unutrašnjih organa. Baš kao i sve nervne ćelije, one sprovode električne signale, šaljući informacije sa svoje lokacije nazad do mozga. Ali, za razlliku od drugih nervnih ćelija, nociceptori se aktiviraju samo ako se dogodi nešto što bi moglo izazvati ili već čini štetu. Dakle, nežno dodirnite vrh igle. Osetićete metal i to je reakcija vaših normalnih nervnih ćelija. Ali nećete osetiti nikakav bol. Sada, što više pritišćete iglu odozgo, to ste bliže pragu nociceptora. Ako pritisnete dovoljno jako, preći ćete taj prag i nociceptor će odreagovati, govoreći vašem telu da prestanete da radite to što radite. Ali, prag bola nije čvrsto postavljen. Određene hemikalije podešavaju nociceptore spuštajući njihov prag bola. Kada su ćelije oštećene, one i ostale okolne ćelije počinju kao lude da proizvode ove podešavajuće hemikalije, spuštajući prag nociceptora do tačke na kojoj i običan dodir može prouzrokovati bol. I tada nastupaju analgetici koji se kupuju bez recepta. Aspirin i ibuprofen blokiraju stvaranje jedne vrste ovih podešavajućih hemikalija po imenu prostaglandini. Hajde da vidimo kako to rade. Kada su ćelije oštećene one otpuštaju hemikaliju po imenu arahidonska kiselina. I dva enzima, COX-1 i COX-2, pretvaraju ovu arahidonsku kiselinu u prostaglandin H2, koji se onda pretvara u čitav niz drugih hemikalija koje vrše čitav niz stvari, kao što je podizanje telesne temperature, uzrokuju upalu i snižavaju prag bola. Sad, svi enzimi imaju neko aktivno mesto. To je mesto u enzimu gde se događa reakcija. Aktivna mesta za COX-1 i COX-2 sasvim se fino uklapaju sa arahidonskom kiselinom. Kao što vidite, nema slobodnog mesta. Ovo je to aktivno mesto gde aspirin i ibuprofen odrađuju svoj posao. I rade na različite načine. Aspirin deluje kao bodlja bodljikavog praseta. Ulazi na aktivno mesto i onda se odlomi, ostavljajući jednu polovinu tamo, potpuno blokirajući taj prolaz i onemogućujući ubacivanje arahidonske kiseline. Ovo trajno deaktivira COX-1 i COX-2. Ibuprofen, s druge strane, ulazi u aktivni prostor, ali se ne raspada niti menja enzim. COX-1 i COX-2 ga mogu ponovo izbaciti, ali dok je ibuprofen prisutan, enzim ne može da veže arahidonsku kiselinu niti da vrši svoju normalnu aktivnost. Ali, kako aspirin i ibuprofen znaju gde je bol? Pa, ne znaju. Kada su lekovi u krvotoku prenose se kroz celo telo i odlaze na mesta gde postoji bol kao i na mesta gde ga nema. Dakle, ovako aspirin i ibuprofen deluju. Ali, postoje i druge dimenzije bola. Neuropatski bol, na primer, je bol prouzrokovan oštećenjem samog nervnog sistema; tu ne mora biti nikakvog vanjskog podsticaja. A nučnici otkrivaju da mozak kontroliše kako mi reagujemo na signale bola. Na primer, koliko bola osećate može zavisiti od toga da li vi obraćate pažnju na bol ili čak od vašeg raspoloženja. Bol je oblast koja se aktivno istražuje.