Understanding Chronic Pain: It’s All About Communication (in the Spinal Cord)


Researchers discover that disrupting the signaling between nerve cells and astrocytes improves pain in mice, early studies in people are underway. Image: A human astrocyte grown in a laboratory dish. Credit: Bruno Pascal, Wikimedia Commons.

In chronic pain conditions, different kinds of cells in the spinal cord communicate with each other in complicated ways. In particular, nerve cells (neurons) that transmit pain signals communicate with glial cells, a type of cell that supports the functioning of neurons.

Now, a new study published January 11 in The Journal of Clinical Investigation identifies a protein that neurons use to interact with astrocytes, a star-shaped kind of glial cell, in mice.

By following changes in the activity of genes in the spinal cord after experimental nerve damage (which is used to study pain in animals), researchers led by Yong-Jing Gao at Nantong University in China discovered increased amounts of CXCL13 in neurons. CXCL13 is a protein known as a cytokine that sends signals to other cells.

The investigators further found that when the neurons released CXCL13, the protein made its way to astrocytes, where it bound to and activated another protein, called CXCR5.

And, of most relevance to chronic pain, the group discovered that nerve-injured animals showed less pain sensitivity in response to touch or heat when communication between CXCL13 and CXCR5 was blocked.

What do these findings from an animal study mean for people who suffer from chronic pain? The researchers think that, if levels of CXCL13 and CXCR5 are altered in individuals with chronic pain, then perhaps disrupting the signaling between the two proteins could also alleviate pain in people.

In preliminary studies, the researchers have found that levels of CXCL13 are in fact elevated in samples of cerebrospinal fluid (a liquid that bathes the brain and spinal cord to protect them from injury) taken from patients with post-herpetic neuralgia. Post-herpetic neuralgia is a condition in which nerve injury produces pain in patients suffering from shingles.

But, much work remains to be done to prove a possible role for CXCL13-CXCR5 communication in chronic pain in people, and whether disrupting that communication will be of benefit. The researchers continue to collect cerebrospinal fluid samples from patients with post-herpetic neuralgia to learn more.

To read about the research in more detail, see the related Pain Research Forum news story here. —Matthew Soleiman

Matthew Soleiman is a neuroscientist-turned-science writer currently residing in Nashville, Tennessee. Follow him on Twitter @MatthewSoleiman