Nociception: Things We Don't Know about Pain

People with congenital insensitivity to pain can feel temperature, but not when it's bad. But those with congenital insensitivity to pain with anhidrosis can't feel temperature at all, and so are at risk of overheating as well as getting cuts, bruises, burns etc. Image credit: Hobbes vs Boyle

Pain evolved as a necessary evil. It tells us when we've done something damaging, or are on the brink of causing more serious harm. It's tempting to wish away pain after stubbing your toe or burning your hand, but life without pain is far from pleasant. People born with very rare genetic conditions giving complete insensitivity to pain end up spending most of their lives in hospital for injuries they simply didn't know they were getting. They must actively learn and constantly be thinking about what things are "bad" to touch, such as knives or boiling water, because they will never feel the warning signs of a light prick or rising warmth.

These people have no trouble experiencing the touch and feel of their surroundings, showing that pain isn't just an excess of touch. Instead, there are nerves which specialise only in detecting and transmitting harmful stimuli. These nerves are called nociceptors.

After the first stage of the transmission of pain signals, our knowledge comes to an end. Image credit: Carlos Martinez

The first step of nociception, how receptors in our skin respond to painful stimuli, is probably the best understood aspect of pain - both mechanical and temperature-based. We know which of the heat-detecting nociceptors^[1] can also be activated by capsaicin, the painful component of chillies that makes us feel like our mouth is on fire despite all evidence to the contrary. We also know which gene is mutated in many people who cannot feel pain.

Yet after the first stage, our understanding wanes considerably.