1.5 billion people suffer from chronic pain. Neuroimmune mechanisms underlie pain chronification. These six hypotheses address neuroinflammation, sex differences, and central sensitization.
Albrecht et al. demonstrated glial activation in fibromyalgia patients using TSPO PET imaging. This provides a biological substrate for a condition long dismissed as "functional."
Anti-neuroinflammatory therapies (e.g., low-dose naltrexone) will reduce symptoms in fibromyalgia patients with imaging-confirmed CNS glial activation.
Combination neuromodulation (CGRP pathway) plus anti-inflammatory therapy will outperform either alone in migraine prevention.
Microglial inhibitors will be more effective in men; T-cell-targeting therapies more effective in women, reflecting sex-specific neuroimmune mechanisms.
A multi-modal central sensitization index will predict treatment response better than clinical diagnosis alone.
Microbiome profiling will identify patients likely to respond to gut-targeted interventions for chronic pain.
Combined anti-neuroinflammatory treatment plus intensive rehabilitation will produce greater and more durable pain reduction than either alone.