Important protein for pain regulation discovered

Although trying to prevent pain does not cure anyone from a disease or injury, it is arguably one of the most important things doctors can do for a patient. Pain relief increases feelings of well-being tremendously, which is why scientists still devote resources to discovering how the body regulates these feelings, despite the fact that we have already have access to a rather large library of painkillers. A recent study from John Hopkins University shows that modifying a certain protein may help us create a new class of such drugs, but it also tells us more about how the body regulates pain.

mGluRs
Feelings of pain are generated from sensory neurons that send their signals to the brain, after which we become aware of the distress. Nerve cells need receptors in order to accept incoming signals, and a substance called glutamate plays an important role in such neural communication. In order to create painful sensations, it is necessary to accept the incoming signal, which is governed by specific glutamate receptors on the neural surface. They activate the necessary pain signals, which also means these receptors, called mGluRs, are a target for scientists in order to develop painkillers.

Preso1
Neurons cannot be activated all the time, otherwise we would constantly be feeling pain. That means there is a need for an inhibitory system, which is governed by a protein called Homer. When this protein binds to the mGluR, it is inactivated and does not respond to glutamate anymore. It was however unclear how this works exactly, explaining why the scientists took interest in investigating said receptor. More knowledge about the mechanism is of course beneficial for the discovery of new painkillers. A study in mice revealed yet another protein, called Preso1, is important for binding Homer to a mGluR, as is visualized below.

An overview of all the interactions mentioned above. Glutamate, coming from somewhere outside the neural cell activates the mGluR and consequently the neuron. But when Homer binds to the receptor (from inside the cell), aided by Preso1, the activity is inhibited. There are many more molecules involved, but these are omitted for clarity.

Target
The newfound function of Preso1 in neurons makes it an obvious target for pain reduction. Experiments with genetically modified mice showed that without Preso1, pain sensations last much longer. That means artificially increasing the level of Preso1, or mimicking its function with a drug, may help to decrease pain. Additionally, the scientists note that mGluRs play a role in other areas as well: preventing activation of the receptors may help to treat patients with alzheimer's disease and schizophrenia.