The red hot (painful) chili peppers

25 February 2009


They're a crucial ingredient in  fiery chilli, and if you don't wash your hands carefully after handling them, you'll discover quite how burning hot they can be, especially if you rub your eyes. Chilli peppers contain capsaicin - the chemical that gives them their fiery heat, but is also a powerful irritant. But in fact, this burning power could be used to reduce pain, according to research published in PloS Biology this week.

Chilli peppersThis is work by Feng Qin and Jing Yao, and they've been investigating how capsaicin can shed light on how our bodies respond and adapt to painful stimuli.

Adaptation is a crucial part of our sensory system, and we know it happens for some of our senses - for example, our hearing and eyesight can adapt very easily to changes. Say you go from a bright room into a dark one. Very quickly, your eyes will adjust so you can detect changes in the light intensity in the dark.  But it's not clear in the case of pain receptors whether they truly adapt - that is, they scale up or down their responses depending on the situation, or whether they just get desensitised to any stimulus and shut down.

The scientists have used capsaicin to investigate how nerves respond to pain. When capsaicin hits a nerve cell, it triggers a wave of calcium to flood into the cell. And depending on the type of nerve, the brain either interprets this as pain or heat.

This pain and heat effect happens with relatively low concentrations of capsaicin. Other scientists have discovered that if you rub large amounts of capsaicin onto the skin, as well as triggering sensations of heat or pain through calcium signalling, it also causes nerve cells to show a drop in levels of a molecule called PIP2. And this causes desensitisation to pain.

In fact, this effect is so powerful that capsaicin creams are sold in pharmacies as treatment for muscle and joint aches, and even for pain caused by arthritis and neuropathy. But what we don't know is how the activation of the receptors by calcium is linked to the drop in PIP2 and subsequent desensitisation.

The researchers used a range of techniques to measure how the pain receptors responded to capsaicin, and found that the drop in PIP2 is directly linked to the activation on the nerve cells by capsaicin, causing the calcium flood. The scientist also showed that even when the receptors are apparently desensitised by capsaicin, they can still respond to a new, higher dose of the chemical.

So this tells us that they're not truly desensitised - otherwise they wouldn't respond at all. In fact, the pain receptors are adapting. They're getting used to a certain level of stimulation from the capsaicin, which gives the sensation of pain relief. But higher doses of capsaicin, or more intense pain, would leak through.

The research has big implications for pain relief, which could be very relevant for doctors trying to relieve pain in patients. With nerve cells that adapt, rather than become truly desensitised, there is no fixed threshold above which they shut off and stop responding. So effectively, the intensity of pain that you experience depends on the level of pain you're recently felt.  At a trivial level, this suggests that if you kick someone in the leg, you should kick them twice because it will hurt less the second time. But it's also important for doctors, because finding ways to manipulate pain-sensing nerves is vital for developing effective painkillers and anaesthetics.


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