Thursday , January 21 2021

The pain control mechanism can be used as a new drug target

Researchers in Japan have discovered a previously unknown pain control mechanism involving a newly identified group of cells in the spinal cord, offering a potential goal of enhancing the therapeutic effect of chronic pain medications.

While neurons may be the most prominent cells of the central nervous system, an assortment of non-neuronal cells first discovered in the mid-nineteenth century also plays a wide range of important roles.

Originally named after the Greek word for “glue”, it is now known that these glial cells are much more than glue and are in fact critical elements in regulating the development and functioning of neurons in the central nervous system.

Among the different types of glial cells, astrocytes are the most common in the central nervous system, but, unlike neurons in different brain regions, researchers have not yet developed a detailed understanding of grouping astrocytes with special properties.

Now, researchers led by Makoto Cuda, a professor in the Faculty of Pharmacy at Kyushu University, have discovered a unique population of spinal cord astrocytes with a role in creating pain hypersensitivity.

Found in the outer two layers of gray matter near the back of the spinal cord – a location called the superficial laminae of the dorsal horn – astrocytes are in a region known to carry general sensory information such as pressure, pain, and heat. from around the body to the brain.

Using mice, the researchers showed that the stimulating noradrenergic (NAergic) neurons – the so-called called for their use of noradrenaline as a neurotransmitter – which carry signals from the locus coruleus (LC) in the brain to the dorsal dorsal horn activate astrocytes and that astrocyte activation results in pain hypersensitivity.

These excitations disprove the prevailing view that descending LC-NAergic neurons suppress pain transmission to the dorsal dorsal horn.

“The discovery of this new population of astrocytes reveals a new role for descending LC-NAergic neurons in facilitating the transmission of pain in the spine,” explains Cuda.

In view of these findings, suppressing the signaling of these astrocytes with norepinephrine may enhance the effect of chronic pain medications.

To test this initially, the researchers genetically engineered mice in which noradrenaline astrocyte reactivity was selectively inhibited and gave them duloxetine, an analgesic drug thought to increase noradrenaline levels in the spinal cord by preventing uptake. of LC-NAergic neurons.

Indeed, the modified mice showed increased relief of chronic pain with duloxetine, further supporting the researchers’ suggested role of astrocytes.

“Although we still need more studies with different drugs, this population of astrocytes seems to be a very promising target for improving the therapeutic potential of chronic pain drugs,” Cuda said.

Reference: Kohro Y, Matsuda T, Yoshihara K. et al. The vertebral astrocyte in the brainstem of the superficial laminae is the gateway to the declining control of mechanosensory hypersensitivity. Nat Neuros 2020; 23: 1376-1387 doi: 10.1038 / s41593-020-00713-4

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