Astrocyte store-operated calcium entry is required for centrally mediated neuropathic pain

bioRxiv preprint, 2023 · DOI: https://doi.org/10.1101/2023.06.08.544231 · Published: June 9, 2023

Simple Explanation

Central sensitization, a key factor in chronic neuropathic pain, involves changes in the spinal cord's nociceptive circuitry. This leads to dysfunction of GABAergic cells, amplification of pain signals, and hypersensitivity. Astrocytes, brain cells, play a crucial role in these neurocircuitry changes. They respond to and regulate neuronal function using complex calcium signaling mechanisms. This study investigates the role of store-operated calcium entry (SOCE) in astrocytes. SOCE is a mechanism where calcium flows into the cell when calcium stores in the endoplasmic reticulum are depleted.

Study Duration

7 Days

Participants

Adult Drosophila melanogaster

Evidence Level

Not specified

Key Findings

1
Astrocytes exhibit SOCE-dependent calcium signaling three to four days after nerve injury in a Drosophila model.
2
Suppressing Stim and Orai, key mediators of SOCE, in astrocytes inhibits the development of thermal allodynia and the loss of GABAergic neurons after injury.
3
Constitutive SOCE in astrocytes results in thermal allodynia even without nerve injury, suggesting SOCE is sufficient for this condition.

Research Summary

This study demonstrates that astrocyte SOCE is necessary and sufficient for central sensitization and the development of hypersensitivity in Drosophila. The research adds new understanding to the astrocyte calcium signaling mechanisms involved in chronic pain, highlighting the importance of SOCE in the process. The findings suggest that astrocyte SOCE is activated in response to neurotrauma and is essential for neural circuitry changes that underlie central sensitization and chronic neuropathic pain.

Practical Implications

Therapeutic Targets

Identifying astrocyte SOCE as a key player in neuropathic pain opens avenues for new therapeutic targets.

Understanding CNS Adaptations

The study enhances the understanding of central nervous system adaptations following nerve injury.

Conserved Roles of SOCE

SOCE may play fundamental and highly conserved roles in multiple aspects of astrocyte physiology.

Study Limitations

1
The study is conducted in Drosophila, and findings may not directly translate to mammals.
2
The specific targets of SOCE in astrocytes and how they regulate astrocyte functions remain to be determined.
3
It is not clear whether SOCE-regulated astrocyte function is directly responsible for GABAergic neuron loss.

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