Astrocytes are recognized as key regulators of neuroimmune interactions, significantly contributing to both the development and progression of chronic pain and neurodegenerative diseases (NDDs) such as Alzheimer’s and Parkinson’s. These glial cells are involved in modulating the immune response, maintaining the blood-brain barrier (BBB), and influencing neuronal activity. Their role in neuroinflammation, aging and chronic pain highlights their importance in central nervous system (CNS) pathology.

Mast cells, traditionally associated with allergic reactions, have emerged as pivotal players in neuroimmune communication. These cells are now known to infiltrate the CNS under pathological conditions, releasing inflammatory mediators influencing astrocytic function. Mast cells and astrocytes engage in bidirectional communication, where mast cell degranulation can trigger astrocytic activation, contributing to neuroinflammation and BBB disruption. This is especially relevant in the context of chronic pain and neurodegeneration, where mast cells amplify inflammatory cascades exacerbating astrocytic dysregulation.

Recent research has shown how astrocytes contribute to chronic pain through the release of pro-inflammatory mediators and the regulation of neurotransmitter signaling, exacerbating pain perception and central sensitization. Furthermore, astrocytic dysfunction is implicated in the progression of NDDs, where they can both exacerbate and mitigate neuronal damage through their interactions with immune cells and their control over neuroinflammatory responses. These cells play a dual role in helping maintain neural homeostasis under physiological conditions or driving disease when dysregulated, particularly in the aging brain. Astrocytes also play a role in blood-brain barrier integrity and neurovascular coupling, demonstrating that they are central not only to immune activation but also to broader disease mechanism. However, the astrocyte-immune communication remain unclear, requiring further research to understand age-related changes that heighten these conditions.

The study of astrocyte-immune interactions offers potential for novel therapeutic strategies targeting astrocytes to mitigate chronic pain and neurodegenerative disease progression. This Research Topic seeks contributions on recent advancements that could lead to better treatments, reducing societal impacts and improving patient care. We welcome Original Research, Reviews, Mini Reviews, and Perspectives covering, though not limited to, the following subtopics:

- astrocyte-immune interactions in pain and neurodegeneration: exploring how astrocytes regulate immune responses and signaling in chronic pain and NDDs.

- astrocyte-driven neuroinflammation and BBB integrity: investigating astrocytic roles in neuroinflammatory processes and their impact on BBB stability during pathological conditions.

- mast cell-astrocyte communication in neuroinflammation: examining the role of mast cells in modulating astrocytic activity and contributing to CNS pathologies.

- calcium dynamics in astrocyte-neuron and immune communication: examining intracellular calcium signaling in astrocytes as a crucial mediator of interactions with neurons and immune cells.

- astrocyte contributions to pain sensitization and aging: understanding how astrocytes influence central sensitization in chronic pain and how aging alters their interactions with neural and immune systems.

- targeting astrocytic pathways in therapy progression: developing therapeutic strategies that target astrocytic mechanisms for managing chronic pain and neurodegenerative diseases.

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Astrocytes and Immunity: Unveiling Their Role in Pain and Neurodegenerative Disease Progression