Multifaceted Astrocyte-Neuron Cross-Talk in Neuropathic Pain: Potential Mechanisms and Functional Implications

Neuropathic pain is a prevalent and debilitating chronic condition with complex and incompletely understood mechanisms. Growing evidence has uncovered astrocytes as active and dynamic regulators in both the initiation and persistence of neuropathic pain. Beyond their classical supportive roles, astrocytes undergo profound morphological and functional remodeling following nerve injury and engage in extensive bidirectional communication with neurons. Through direct physical contacts, gliotransmitter release, and complex intercellular signaling networks, astrocytes critically shape synaptic plasticity, neuroinflammatory cascades, and neuronal excitability, ultimately driving maladaptive pain processing. In this review, we provide an updated and integrative overview of astrocyte-neuron cross-talk in neuropathic pain, with a particular focus on the molecular and cellular mechanisms by which astrocytic signaling modulates synaptic remodeling and pain sensitization. A deeper understanding of these astrocyte-mediated interactions may open new avenues for the development of precise and targeted therapeutic strategies for neuropathic pain.