Towards a Whole-Body Assessment of Pain Using the 18 kDa Translocator Protein (TSPO) as a Broad-Spectrum Imaging...

Chronic pain is increasingly understood as a systemic condition involving coordinated immune responses across central and peripheral compartments. In this narrative review, we present evidence supporting positron emission tomography (PET) imaging of the translocator protein (TSPO), long considered a marker of neuroinflammation, as a promising tool to visualize inflammation throughout the body.

This narrative review synthesizes published evidence from TSPO PET studies in chronic pain. We first provide a concise overview of central nervous system (CNS) applications across various chronic pain conditions, implicating neuroinflammation as a potential pathophysiological mechanism underlying human chronic pain. We then discuss evidence from studies extending this imaging approach beyond the CNS to peripheral tissues, in which TSPO is highly expressed by immune cells. We also review associations between these imaging signals, clinical measures and circulating cytokine levels.

Compared with controls, patients with chronic pain show elevations in TSPO PET signal not only within the CNS, including the brain and spinal cord, but also in peripheral structures such as the neuroforamina and joints. Correlations with clinical measures and systemic cytokine levels underscore the potential clinical significance of these peripheral signals. This expanded view positions TSPO PET as a broad-spectrum marker of inflammation, enabling a unified imaging modality that bridges traditionally siloed approaches to pain research, while also facilitating the discovery of previously underappreciated pain-relevant tissues and immune compartments. Of particular relevance, the application of TSPO PET beyond its traditional CNS focus has revealed a previously unrecognized role for CNS-adjacent immune niches, such as skull bone marrow, in human chronic pain.

With further evaluation, TSPO PET may provide a means of visualizing inflammatory processes across multiple pain-relevant compartments, paving the way for a whole-person approach to the study of human chronic pain.

TSPO PET is not merely a neuroimaging tool but could serve as a systemic marker of inflammation in chronic pain. By enabling a whole-person framework for studying pain and inflammation, it has the potential to inform precision medicine approaches and guide therapeutic decisions.