Glial cells in neuropathic pain

Neuropathic pain is a chronic, debilitating condition that affects ∼7-8% of the global population and remains difficult to treat because of limited therapeutic options. Over the past two decades, mounting preclinical evidence has highlighted the crucial role of glial cells in the development, maintenance, and resolution of neuropathic pain. Conditions such as peripheral nerve injury are associated with reactive responses of glial cells, namely microglia and astrocytes in the central nervous system and satellite glial cells in the peripheral ganglia. Under physiological conditions, glial cells contribute to homeostatic regulation of spinal nociceptive circuits, preserving normal pain sensitivity. However, neuropathic pain is increasingly recognized as a form of gliopathy, wherein dysregulated glial activity contributes to pain hypersensitivity through enhanced excitability of primary sensory neurons (peripheral sensitization) and neuronal plasticity in the central pain circuits (central sensitization). In this review, we provide a comprehensive overview of glial cell research in neuropathic pain, with a specific focus on microglia, astrocytes, and satellite glial cells, the most extensively studied glial types in this context. We also highlight the critical involvement of glial cells in neuroinflammation and neuro-glial interactions and evaluate emerging therapeutic strategies targeting glial mechanisms of neuropathic pain.