Astrocyte Contribution to Pain Signaling

Building a Case for the Astrocyte Contribution to Pain Signaling | Pain Research Forum

Mouse study presented at Neuroscience 2013 in San Diego shows that chemokines released through astrocyte hemichannels sensitize spinal cord neurons

Glial cells have recently emerged as important regulators of chronic pain, particularly in the spinal cord where they contribute to the neuronal sensitization thought to underlie neuropathic pain hypersensitivity. Among glial cells, microglia have garnered most of the attention so far, but astrocytes are increasingly recognized as major players in chronic pain

Astrocytes and pain hypersensitivity  

“Accumulating evidence shows that astrocyte activation [in the spinal cord following nerve injury] could be long-lasting and more persistent than the microglial reaction, indicating that astrocytes can play a key role in pain maintenance distinct from microglial mechanisms,”

Ji’s team showed that spinal cord astrocytes release the chemokine CCL2

they also showed that another chemokine, CXCL1, and its receptor CXCR2, were upregulated in astrocytes and neurons, respectively, and contributed to pain hypersensitivity in the spinal nerve ligation model of neuropathic pain in mice

Ji described chemokines as smaller versions of cytokines, the inflammatory signaling peptides released from many immune cells and from astrocytes

Gap junctions serve to fasten two neighboring astrocytes together by forming a pore that passes through the membrane of both cells, connecting their cytoplasm. To form the passageways, each of the two adjoining cells contributes one hemichannel protein; in astrocytes, that protein is Cx43

Gap junctions allow signaling molecules such as ATP, glutamate, and calcium to pass freely from cell to cell, endowing astrocytes with rapid communication capabilities.

Individual Cx43 hemichannels can also open to the extracellular space, providing a portal for release of astrocytic mediators such as chemokines.

Following nerve injury, astrocytes lose functional gap junctions, so Ji postulated that the cells might switch from fast gap-junction signaling to slower paracrine signaling through Cx43 hemichannels.

functioning Cx43 pores were required for mechanical hypersensitivity.

Electrophysiological experiments further indicated a role for Cx43 in mediating long-term pain hypersensitivity



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