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Updated: Jun 8, 2026
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Intracranial Pharmacotherapy and Pain Assays in Rodents
Published on: April 9, 2019
Targeting astrocyte signaling for chronic pain
1Department of Anesthesiology, Sensory Plasticity Laboratory, Pain Research Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. yjing@zeus.bwh.harvard.edu
Summary
Astrocytes in the central nervous system contribute to chronic pain by releasing inflammatory molecules like interleukin-1β and monocyte chemoattractant protein-1. Targeting these astrocyte signaling pathways offers potential new treatments for neuropathic and cancer pain.
Area of Science:
- Neuroscience
- Pain Research
- Cellular Biology
Background:
- Chronic pain management is challenging due to limited understanding of underlying cellular mechanisms.
- Glial cells, particularly astrocytes, are increasingly recognized for their role in chronic pain development and maintenance.
- Astrocyte reactivity correlates strongly with chronic pain behaviors, persisting longer than microglial responses.
Purpose of the Study:
- To investigate the role of astrocyte-derived signaling molecules in chronic pain.
- To explore the potential of targeting specific astrocyte signaling pathways for pain management.
Main Methods:
- Examined the release of pro-inflammatory cytokines (IL-1β) and chemokines (MCP-1/CCL2) from activated astrocytes in the spinal cord.
- Investigated the involvement of matrix metalloprotease-2 in IL-1β activation and c-Jun N-terminal kinase in MCP-1 release.
- Assessed the impact of MCP-1 on pain sensitivity via NMDA receptor activation.
- Evaluated the efficacy of pharmacological inhibition of these pathways in preclinical pain models.
Main Results:
- Activated astrocytes release IL-1β and MCP-1, enhancing and prolonging pain states.
- IL-1β modulates spinal synaptic transmission, increasing excitation and decreasing inhibition.
- Nerve injury activates spinal astrocytes' c-Jun N-terminal kinase, increasing MCP-1 release.
- MCP-1 directly increases pain sensitivity by activating dorsal horn neuron NMDA receptors.
Conclusions:
- Specific signaling pathways in spinal astrocytes, including IL-1β, MCP-1, c-Jun N-terminal kinase, and matrix metalloprotease-2, are critical for maintaining chronic pain.
- Pharmacological inhibition of these astrocyte-mediated pathways effectively attenuates various chronic pain types.
- Targeting astrocyte signaling pathways presents a promising therapeutic strategy for managing chronic pain conditions.
