Cognitive Behavioral Therapy and Pain Chronification: Neuroimmune Rationale, Evidence Boundaries, and Trial Design Priorities: A Structured Narrative Review
Abstract
Background Pain chronification is a dynamic transition in which persistent pain may be shaped by interacting nociceptive, peripheral, spinal, supraspinal, neuroimmune, endocrine and cognitive-affective processes. Cognitive Behavioral Therapy (CBT) has clinical value in chronic pain, but claims about glial modulation and disease modification require careful qualification. Objective To evaluate CBT as an early, mechanism-informed and hypothesis-generating intervention while distinguishing clinical efficacy, neuroimmune plausibility, prevention hypotheses and disease-modifying claims. Methods We conducted a structured narrative review using prespecified evidence domains. PubMed/MEDLINE searches covering January 2014 to September 10, 2026 were complemented by citation chasing and selected landmark mechanistic articles. Sources were organized by evidence domain, study type and interpretive role, including pain chronification, neuroimmune and glial mechanisms, brain-network mechanisms, CBT outcomes, psychoneuroimmune pathways, perioperative prevention hypotheses, risk phenotyping and scalable delivery. No quantitative pooling or formal systematic/scoping-review workflow was performed. Results Experimental and translational studies support neuroimmune contributions to central sensitization and pain maintenance, whereas human evidence for direct CBT effects on microglial or astrocytic activation remains insufficient. CBT produces reproducible, generally small effects on pain intensity and more consistent benefits for interference, disability, distress, coping, sleep and function. Conclusion CBT should be presented as a clinically valuable component of multimodal care and as a testable psychoneuroimmune hypothesis, not as a proven preventive, glial-targeting or disease-modifying treatment. Risk-stratified, early, component-specific and mechanism-embedded trials are needed before prevention claims are made.