There’s a type of chronic pain that occurs with the lightest of touch, and it is infuriating. For some, just having clothing touch their skin sends them into agony. Hopefully, there may be a treatment on the horizon now that scientists have found a possible avenue for producing painkillers that specifically target and treat this kind of pain.
In a study published online today in eLife, they discovered how the stiffness of our nerve cells influences sensitivity to touch and pain.
“Being able to stop this mechanical pain could be very powerful, and it’s something that current drugs are not very good at doing,” says Paul Heppenstall, who led the work at the European Molecular Biology Laboratory (EMBL).
When one is touched either slightly or with some force, receptors on the nerves under the skin sense it and carry that information to the brain. Those receptors detect and respond to the actual bending of the nerve cell’s membrane, and now scientists have discovered the molecule that affects how sensitive a mouse is to touch and pain. Scientists have figured out how to influence how stiff or “bendy” a nerve cell is, and that shows promise for future developments.
The researchers genetically engineered mice so that they were unable to produce a molecule called Atat1. They found that the nerve cells in the affected mice became stiffer and insensitive to light touch and to mechanical pain. This happened both when they prevented all of a mouse’s cells from producing the molecule and when they did so just in the mouse’s sensory neurons.
The Atat1 molecule is present in all cells. Its role is to modify microtubules – tiny tubes that act as transport network and scaffolding inside cells – and that this happens in all cells, especially in nerve cells.
“It could be that the molecule also affects the stiffness of nerves involved in other senses, but because stiffness is not important for detecting smells or tastes, for example, changes in cell stiffness might not have a detectable effect on those senses,” says Shane Morley, who carried out the work at EMBL.
They found that the difference between nerve cells that detect touch and other cells is how the microtubules are arranged. In sensory cells, they form a ring just below the cell membrane, while in other cells, they don’t. The scientists think that this ring probably fine-tunes how stiff or bendy a nerve cell’s membrane is, influencing how sensitive that cell is to touch.
“We’re now looking for small molecules that interfere with this fine-tuning of cell stiffness, and which might one day be used to make painkillers specifically to treat this mechanical pain,” Heppenstall said. “This is the first step in our sense of touch, so if we can stop the signal there, then we have a good chance of stopping everything which is downstream. And because only these touch-sensing nerve cells would be affected, there’s hope that such a drug might not have many unwanted side-effects.”