PRIN PNRR
NextGenerationEU
Project details

ENU Team Leader: VALENTINA ALDA CAROZZI

Coordinator: ANTONIO ZIPPO (CNR), PI
Other Participants: CLAUDIA GUARNIERI (CNR)


Total Contribution: 299000 €


Project Duration in months: 24
Start Date: December 2023
End Date: December 2025

Abstract

Chronic pain (CP) is a severe and disabling condition which affects millions of people worldwide and it is commonly characterized by allodynia, dysesthesia and hyperalgesia, symptoms poorly managed by current interventions. Interestingly, CP may become independent from the originating causes and its comprehensive etiology remains unclear. As a rule, peripheral injury provokes hyperactivity of somatosensory neurons, a condition that triggers profound long-term changes along the somatosensory and nociceptive ascending pathways. In a special type of neuropathic pain, i.e. the deafferentation pain which occurs in case of amputation or traumatic events, the corresponding somatotopic area tends to expand into the adjacent somatotopies resulting in a partial reorganization of the primary somatosensory cortex (S1) somatotopies. Specifically, by axonal sprouting, supragranular and subgranular cortical layers increase the horizontal connections with neighboring cortical columns. Another chronic neuropathic pain model, the sciatic nerve ligature (SNL), produces a chronic neuropathy to one of the sciatic nerves which is expressed by allodynia and hyperalgesia 7-10 days after the surgical event. SNL reflects several types of peripheral neuropathies where nerves are mechanically compressed as in case of herniation, neoplasm development and it affects a vast portion of chronic pain patients. However, a detailed investigation of the cytoarchitectural and electrophysiological correlates of this class of neuropathic pain is missing. Another relevant class of peripheral neuropathic pain is represented by the chemically-induced painful neuropathy (CIPN) which includes a large spectrum of peripheral neuropathic conditions produced by the usage of chemotherapeutic agents such as taxanes, platinum-based compounds and proteasome inhibitors. No effective treatment is available at the moment and the only option to prevent severe and permanent neurological damage of cancer patients is to reduce or withdraw the anticancer treatment, impacting on their long term oncological outcome. From a therapeutic perspective, lateral cortical connectivity, parallel to the cortical surface, can be targeted by cuttingedge technologies. Synchrotron generated X-ray beams at high-energy are collimated with micrometric precision and release huge and rapid ionizing radiations. Biological tissues receiving such a radiation dose undergo fast cellular apoptosis. In other words, this tool acts as surgical knives with unprecedented precision for biological tissues without relevant side effects. The technique has already found pre-clinical applications for epilepsy. Therefore, this technology offers a cutting-edge method to disrupt the inflated cortical horizontal connections developed as results of persistent peripheral neuropathies. Preliminary data from SNL rats looks encouraging. The project would develop precise noninvasive therapies for CIPN and SNL models in a pre-clinical context.

Cortical lateral connectivity in the pathogenesis of neuropathic pain: a target for non-invasive radiosurgical therapies