The Influence of Microglial and Astrocytic Responses on Neuronal Survival and Plasticity in Neuropathic Pain States

Abstract

Neuropathic pain is a chronic condition that results from injury or disease affecting the somatosensory nervous system, leading to persistent pain, hyperalgesia, and allodynia. Central to the development and persistence of neuropathic pain are the responses of glial cells, particularly microglia and astrocytes, which significantly influence neuronal survival and plasticity. Upon nerve injury, microglia are rapidly activated, leading to the release of pro-inflammatory cytokines, chemokines, and neurotrophic factors that contribute to neuronal sensitization and synaptic remodeling. Microglia-induced neuroinflammation can exacerbate neuronal injury, but they also play roles in promoting repair under certain conditions. Astrocytes, which become reactive following nerve injury, modulate synaptic function and maintain the homeostasis of the extracellular environment. Reactive astrocytes release both pro- and anti-inflammatory factors and engage in complex interactions with neurons and microglia, influencing synaptic plasticity and contributing to the persistence of pain states. This review explores the mechanisms through which microglial and astrocytic responses affect neuronal survival and synaptic plasticity in neuropathic pain. We discuss the signaling pathways, such as NF-$\kappa$B, MAPK, and purinergic signaling, that mediate glial activation and their downstream effects on neuronal function. Additionally, we highlight potential therapeutic strategies aimed at modulating glial activity to alleviate chronic pain and promote neuronal health. Understanding the roles of microglia and astrocytes in shaping the neuronal environment provides insights into new approaches for managing neuropathic pain and improving neuronal resilience.