Pain and pain-related conditions cause the highest burden of disease and are the leading cause of disability globally. Discovery of the glymphatic system provides new perspectives into the pathogenesis of chronic pain and opportunities for its treatment and prevention. The glymphatic system is active under natural deep sleep enabling the cerebrospinal fluid to flow through the brain and to clear the central nervous system of accumulated waste. This multidisciplinary preclinical study will be performed in rodents using state-of the art methods, such as a novel single-photon emission tomography tracking of cerebrospinal fluid flow. We will assess the hypothesis that pain-induced poor sleep leads to impaired glymphatic flow, poor clearance of proinflammatory cytokines, neuroinflammation, and consolidation of the chronic pain state. Ultimately, we will study if preclinically identified glymphatic enhancers could be used in rescuing glymphatic flow to alleviate chronic pain.

2022

2026