Pain medicine: Inhibitor protein against chronic pain discovered

Table of contents:

Pain medicine: Inhibitor protein against chronic pain discovered
Pain medicine: Inhibitor protein against chronic pain discovered

Inhibiting protein against chronic pain discovered

The nerve cells in our spinal cord have a previously unknown protective mechanism against severe pain, reports an international research team led by Anke Tappe and Rohini Kuner from Heidelberg University Hospital. The discovery opens up completely new perspectives for the treatment of chronic pain.

The scientists looked at the so-called "Homer" proteins, which were discovered in the limbic system of the cerebrum nine years ago. Emotions and the perception of pain are processed in this area of the brain. The Homer proteins act as adapter proteins that play a role in the transmission of signals from the body to the processing cell systems: they connect the receptor proteins for the messenger substance glutamate with the calcium receptors in the cell membrane via a molecular framework.

© Heidelberg University Hospital (detail) How is pain memory created? | The protein Homer 1a acts as an inhibitor (right image) when pain receptors (nociceptors) are repeatedly stimulated (left image). When stimulated, the messenger substance glutamate binds to a receptor ("mGluR", green), which then transmits a signal via an IP3 signaling cascade; Here, Homer proteins ("Homer 1", blue) play an important role as molecular bridge builders. If the Homer proteins form the bridge (left picture), the incoming glutamate signal ultimately ensures calcium release and the formation of a pain memory.

The now discovered "Homer 1a" (picture on the right, red) can prevent the formation of the Homer bridge - and thus also the development of pain memory and chronic pain.

The researchers have now been able to show for the first time that the adapter proteins are also found in the spinal cord and are involved in pain processing there. They also revealed that the small Homer protein 1a can disrupt the construction of the transport framework required for signal transmission. Homer 1a is produced in abundance by the body, especially in the case of protracted inflammation. However, if its inhibitory effect fails, pain is perceived permanently because the other Homer proteins build up a pain memory undisturbed: the pain becomes chronic.

"Until now, we only knew feedback mechanisms that increase pain," say the scientists. "With Homer 1a we identified for the first time a negative feedback mechanism in pain processing."

This is of little importance for acute pain, which is a sensible warning signal. However, chronic pain, which has largely lost its meaning and warning character, would be even less bearable without the protection of the body's own emergency brake Homer 1a.

The study shows that the higher the concentration of Homer 1a in the spinal cord, the less pain is felt. This could possibly be used therapeutically by introducing the blueprint for this protein into the affected cells in gene therapy. However, it would probably be easier to mold small parts of Homer 1a, with which he breaks down the pain bridge, and to develop them into a drug. © Heidelberg University

Popular topic