Cortical microvessels and the tripartite synapse in chronic pain studied with synchrotron radiation

Chronic pain (CP) is a complex sensory disorder characterized by persistent pain sensation, which continues for months or years even after the original cause of pain (illness, or injury) is resolved. Medically, the status of chronic pain is defined when pain lasts more than 3 months; it affects millions of people worldwide and it is treated with strong pain killers. The exact origin of this persistency is not known; however, brain structural and functional changes are observed by fMRI and PET at the level of thalamus and somatosensory cortex in CP patients. The aim of this Thesis was to investigate whether the macroscopic functional modifications are associated and may originate from microscopic vascular and neuronal changes in the brain cortex. The 3D microarchitecture of cortical vascular network was studied by means of synchrotron X-ray micro and nano Computed Tomography (CT) imaging at the ID17 and ID16A beamlines (ESRF) and at TOMCAT (PSI). A comparative study “Neuropathic vs Control” showed evident changes in cortical microvascular compartments: a widespread increase of blood microvessels and capillaries in the investigated regions has been found in all CP rats. By investigating the time evolution of the neogenesis, it appeared strongly present since the first stage of the neuropathy (2 weeks), fading away, but still present, during the last time stage examined (6 months). The micro- and nano-tomography findings have been further confirmed also by immunofluorescence microscopy analysis. In parallel, to functionally analyse the genesis and the evolution of the thalamo-cortical circuits in CP conditions, the neural activity was also recorded in our animal models. All the CP groups showed connectivity disorders in neuronal information transmission. The microvascular involvement in CP opens a new way of interpretation of CP disease, not only recognized as sensory pathology, but also as a neurological disease where neuronal and vascular connectivity networks are extensively involved in the whole system.