The pain control mechanism could be exploited as a new drug target

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

While neurons may be the best-known cells of the central nervous system, an assortment of non-neuronal cells first discovered in the mid-nineteenth century also play a wide variety of important roles.

Originally called from the Greek word for “glue,” these glial cells are now known to be much more than glue and are indeed critical to regulating neuronal development and function in the central nervous system.

Of the different types of glial cells, astrocytes are the most abundant in the central nervous system, but, unlike neurons in different regions of the brain, researchers have yet to develop a detailed understanding of the groupings of astrocytes with distinct properties.

Now, researchers led by Makoto Tsuda, a professor at Kyushu University’s Graduate School of Pharmaceutical Sciences, have discovered a unique population of spinal cord astrocytes with a role in producing pain hypersensitivity.

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

Using mice, the researchers demonstrated that stimulation of noradrenergic (NAergic) neurons – so named for their use of norepinephrine as a neurotransmitter – that carry signals from the locus coeruleus (LC) in the brain to the spinal dorsal horn activates astrocytes and that the activation of astrocytes causes hypersensitivity to pain.

These observations overturn the prevailing view that descending LC-NAergic neurons suppress pain transmission in the spinal dorsal horn.

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

Considering these findings, norepinephrine’s suppression of these astrocytes signaling may enhance the effect of chronic pain medications.

To initially test this, the researchers engineered mice in which the response of astrocytes to norepinephrine was selectively inhibited and gave them duloxetine, an analgesic drug thought to increase norepinephrine levels in the spinal cord by preventing absorption by LC neurons. -Nergic descendants.

In fact, the modified mice showed greater relief of chronic pain by duloxetine, further supporting the researchers’ proposed role of astrocytes.

“While we still need more studies with different drugs, this population of astrocytes appears to be a very promising target for increasing the therapeutic potential of chronic pain drugs,” Tsuda says.

Reference: Kohro Y, Matsuda T, Yoshihara K. et al. Spinal astrocytes in the brain stem descending control of the superficial laminae gate of mechanosensory hypersensitivity. Nat Neurosci 2020; 23: 1376-1387. doi: 10.1038 / s41593-020-00713-4

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