Chronic pain is associated with greater brain entropy in the prefrontal cortex.

Chronic pain is a debilitating clinical condition and a severe public health issue that demands to be addressed. Neuroimaging-based techniques have been widely adopted to investigate the neural underpinnings of chronic pain. Despite the efforts the complex nature of pain experience as well as the heterogeneity of chronic pain have made the identification of neuroimaging-based biomarkers extremely challenging. In this study, resting-state fMRI-based brain entropy, a measure reflecting the "irregularity" of brain activity, was adopted as a biomarker of chronic pain by comparing individuals with chronic pain and healthy controls in a sample of middle-to-old-age participants (n > 30,000) drawn from the UK Biobank database. Abnormal brain entropy is associated with altered brain dynamics and may serve as a potential marker of disrupted pain processing in individuals with chronic pain. Compared to healthy controls, individuals with chronic pain exhibited increased brain entropy in a broad set of regions including the frontal, temporal, and occipital lobes, as well as the cerebellum. In addition, individuals with a more distributed chronic pain showed increased brain entropy in occipital lobes. When examining distinct types of chronic pain individually, only participants with headache and pain all over the body showed brain entropy differences compared to a matched sample of healthy controls. PERSPECTIVE: This article investigates the neural substrates of chronic pain using brain entropy, a measure of the randomness and irregularity of brain activity. This measure could potentially aid in the assessment and treatment of chronic pain.