The Role of Glial Cells in Chronic Postsurgical Pain: A Narrative Review

Abstract

Chronic postsurgical pain (CPSP) remains a major global clinical problem, affecting a substantial proportion of patients and contributing to persistent pain, functional impairment, and reduced quality of life after surgery. The multifaceted nature of pain chronification hinders effective prevention and treatment, underscoring the need to understand its underlying mechanisms better. This evaluation investigates the neuronal and cellular dynamics that facilitate the transition from acute nociception to CPSP following surgical injury, with a specific focus on glial cell involvement. Tissue injury after surgery triggers peripheral and systemic inflammatory responses, along with the release of damage-associated molecular patterns and other mediators that activate neuroimmune signaling pathways. Microglia, astrocytes, and satellite glial cells then collaborate with peripheral sensory neurons and spinal nociceptive circuits, releasing cytokines, neurotrophic factors, adenosine triphosphate, and excitatory substances that enhance peripheral and central sensitization. Ongoing glial–neuronal and neuroimmune interactions might facilitate aberrant synaptic plasticity and the enduring nature of pain during tissue recovery. A refined grasp of these pathogenic processes may provide new possibilities for prevention and treatment, while also supplying mechanistic supplements to established perioperative pain management techniques. While gabapentinoids and interventions focused on glial pathways show promise, their capacity to avert CPSP has not been conclusively demonstrated. Most glia-targeted therapies are currently experimental and largely supported by preclinical findings; therefore, well-designed clinical research is essential to evaluate their efficacy, safety, and therapeutic role in CPSP.