Chronic pain has long been treated as a localized problem — a bad knee, a herniated disc, a migraine. Emerging imaging evidence now challenges that framing fundamentally, repositioning chronic pain as a systemic inflammatory condition detectable from brain to joint, with implications for both diagnosis and treatment strategy.
This narrative review, published in the European Journal of Pain, synthesizes PET imaging studies using TSPO — the 18 kDa translocator protein expressed primarily on activated microglia and peripheral immune cells — as a whole-body inflammation tracer. The key finding is that chronic pain patients consistently show elevated TSPO PET signal not only in the central nervous system (brain and spinal cord) but also in peripheral structures including neuroforamina and joints. Critically, these peripheral signals correlate with clinical pain measures and circulating cytokine concentrations, suggesting the imaging readout tracks biologically meaningful inflammation rather than artifact. This dual central-peripheral signal pattern positions TSPO PET as a potential broad-spectrum biomarker capable of capturing the full inflammatory architecture of a pain condition in a single imaging session.
The significance here extends beyond radiology. TSPO has been studied as a neuroinflammation marker since the 1990s, but its application was largely confined to CNS conditions like multiple sclerosis and depression. Repurposing it as a systemic pain biomarker is conceptually important because it provides an objective, mechanistically grounded window into a condition that still lacks validated biological markers in clinical practice. That said, this is a narrative review — not a meta-analysis — and TSPO PET carries known limitations: second-generation ligands are confounded by a common polymorphism (rs6971) that affects binding affinity, requiring patient genotyping. Cohort sizes in individual TSPO pain studies remain small, and causality versus correlation cannot be established from imaging associations alone. For now, this represents a promising but early-stage framework that could eventually stratify pain patients by inflammatory subtype and guide anti-inflammatory treatment selection — an incremental but directionally important advance.