How Pain Works

How Pain Works: Pain is not a direct readout of injury but an output built by the brain from nerve signals, context, expectation and emotion, which is why the same wound can hurt wildly differently depending on who has it and when.

Gate Control Theory: Ronald Melzack and Patrick Wall proposed in 1965 that the spinal cord acts like a gate for pain signals, explaining why rubbing a bumped elbow actually dulls the hurt.

Silas Weir Mitchell: The Civil War doctor gave phantom limb pain its name after treating amputee soldiers who felt burning and cramping in arms and legs that no longer existed.

V.S. Ramachandran: His simple mirror box, which tricks the brain into seeing a missing limb move, relieved phantom pain in some amputees in the 1990s using nothing more than a cardboard box and a mirror.

Henry Beecher: Treating wounded soldiers near Anzio in World War II, he found only about a quarter asked for morphine, far fewer than civilians with milder injuries, because the wound also meant survival and a ticket home.

Geoffrey Woods: In 2006 his team traced a total inability to feel pain in a Pakistani family to mutations in the SCN9A gene, identifying a single sodium channel that pain signals depend on.

Jo Cameron: This Scottish woman barely noticed burns, cuts or childbirth, and scientists in 2019 traced her near painlessness and low anxiety to a previously unknown gene they named FAAH-OUT.

Justin Schmidt: The entomologist let dozens of insects sting him to build the Schmidt Sting Pain Index, ranking the bullet ant at the top with a pain he compared to walking over flaming charcoal with a nail in your heel.

David Julius: He won the 2021 Nobel Prize for using chili pepper capsaicin to discover TRPV1, the receptor that makes both real heat and spicy food feel like burning.

Naloxone: In a 1978 dental surgery study, this opioid blocking drug wiped out the pain relief patients got from a placebo, proving placebos trigger the brain's own painkillers.

Hans Kosterlitz: In 1975 he and John Hughes discovered enkephalins in Aberdeen, the first of the body's natural opioids, revealing the brain produces its own morphine like chemicals.

Richard Stephens: His 2009 Keele University study found volunteers who swore could keep their hands in ice water significantly longer than those who repeated a neutral word.

Cyberball: In Naomi Eisenberger's 2003 experiment, people excluded from this simple virtual ball tossing game showed activity in brain areas also linked to the distress of physical pain.

Nathan DeWall: His 2010 study found people who took daily acetaminophen for three weeks reported fewer hurt feelings, suggesting a common painkiller also eases the sting of social rejection.

Henry Head: The British neurologist mapped Head's zones in the 1890s, explaining referred pain, which is why a heart attack can be felt in the left arm or jaw.

Jorge Serrador: His 2012 study had volunteers sip ice water through a straw and found brain freeze coincides with a sudden surge of blood flow in an artery behind the eyes.

Jarred Younger: His 2010 Stanford study found looking at a photo of a new romantic partner reduced pain about as much as some painkillers, activating the brain's reward circuits.

Hunter Hoffman: His virtual reality game SnowWorld, where burn patients throw snowballs at penguins, cut reported pain during wound care by pulling attention away from the injury.

James Esdaile: The Scottish surgeon in 1840s India reported performing hundreds of operations using mesmerism in place of anesthesia, just before ether arrived.

Ether Day: On October 16, 1846, dentist William Morton put a patient under with ether at Massachusetts General Hospital, and the surgeon famously declared that it was no humbug.

Felix Hoffmann: The Bayer chemist synthesized a stable form of acetylsalicylic acid in 1897, turning the willow bark remedy used since ancient times into aspirin.

Ulrike Bingel: Her 2011 study found that when volunteers were told a powerful opioid drip had stopped, its pain relief largely vanished even though the drug was still flowing.

Jeffrey Mogil: His 2014 study found mice showed less pain behavior when male researchers or even their worn T shirts were nearby, a stress response that may have skewed decades of lab results.

WHO Analgesic Ladder: Introduced in 1986 for cancer pain, this three step guide from mild drugs to strong opioids became one of the most influential pain treatment frameworks in the world.

Wong-Baker FACES Pain Rating Scale: Created in 1983 by nurse Donna Wong and child life specialist Connie Baker, its row of cartoon faces lets young children rate pain they can't yet put into words.