title: Neurovascular unit in chronic pain.
abstract: Chronic pain is a debilitating condition with major socioeconomic impact, whose neurobiological basis is still not clear. An involvement of the neurovascular unit (NVU) has been recently proposed. In particular, the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB), two NVU key players, may be affected during the development of chronic pain; in particular, transient permeabilization of the barrier is suggested by several inflammatory- and nerve-injury-based pain models, and we argue that the clarification of molecular BBB/BSCB permeabilization events will shed new light in understanding chronic pain mechanisms. Possible biases in experiments supporting this theory and its translational potentials are discussed. Moving beyond an exclusive focus on the role of the endothelium, we propose that our understanding of the mechanisms subserving chronic pain will benefit from the extension of research efforts to the NVU as a whole. In this view, the available evidence on the interaction between analgesic drugs and the NVU is here reviewed. Chronic pain comorbidities, such as neuroinflammatory and neurodegenerative diseases, are also discussed in view of NVU changes, together with innovative pharmacological solutions targeting NVU components in chronic pain treatment.
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Beatrice Mihaela
authors.initials: BM
authors.lastname: Radu
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.forename: Francesco
authors.initials: F
authors.lastname: Osculati
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Flonta
authors.forename: Mihai
authors.initials: M
authors.lastname: Radu
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bertini
authors.forename: Paolo Francesco
authors.initials: PF
authors.lastname: Fabene
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D059350:Chronic Pain / Q000378:metabolism*; D006801:Humans; D009437:Neuralgia / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
chemical_list: D018528:ATP-Binding Cassette Transporters