Removal of behavioural and electrophysiological signs of chronic pain byin vivomicrosections of rat somatosensory cortex with parallel X-ray microbeams

Abstract

Chronic pain (CP) is a condition characterized by a wide spectrum of clinical signs and symptoms, missing a sound modelling at the neuronal network scale. Recently, we presented a general theory showing common electrophysiological traits in different CP rat models, i.e. a collapse of relevant functional connectivity network properties, such as modularity, in the somatosensory thalamo-cortical (TC) network. In this work, we preliminary investigated by an in silico accurate simulator of the six-layer mammalian cortical networks that evidenced the crucial collapse of network modularity in CP simulated conditions and the consequent reduction of network adaptive processes. On this track, in studies on CP experimental animals affected by sciatic nerve multiple ligature (Bennett-Xie model), by synchrotron-generated X-ray microbeam (MB) irradiations (7 parallel beams, 100um width), we targeted in vivo the CP involved hindlimb somatosensory projection cortex that, because of the doses radiation (360 Gy, peak at each beam), non-invasively produced fast and precise tissue destruction along the 7 beam projections. These parcellated the cortical tissue and restored the cortical network statistics related to modularity and information processing efficiency as evidenced from post irradiation in vivo electrophysiological recordings. In addition, by MB treatment there was an ensuing removal of behavioral signs of allodynia and hyperalgesia accompanied by recovered normal gait schemes yet preserving the normal sensory thresholds of the experimental rats up to three months after the MB irradiation. Finally, novel and unprecedented therapeutic appraisals for CP are devised. Significance StatementChronic pain (CP) is an excruciating condition with severe effects on patients' life. Apart from many clinical and experimental studies no current theory on CP is generally accepted. Recently, we proposed a general theory of CP in experimental animals as characterized by strong alteration of the connections among neurons in different brain regions. We show here on in silico simulations that specific connectivity changes in the somatosensory cortex recover the lost functional integrity. Concurrently, in experimental animals, we re-modulated, in vivo, some anatomical connections of the somatosensory cortex by extremely thin synchrotron generated X-ray microbeam irradiations. The resulting behavioral and electrophysiological signs of CP disappeared yet maintaining normal sensory responses. No adverse or pathological effects on blank animals were observable.The results report a multianalytic picture of the effects of high-dose sevenfold X-ray microbeams (MBs) irradiation through the intact skull on the somatosensory cortex of experimental rats in vivo anesthetized with a model of neuropathic Chronic Pain (CP, Figure 1A-F) and control (CR). Early computational inspectionsPreliminary, in silico exploratory analyses offered the possibility to evaluate the effects of guided connectivity interventions on functional and topological substrates of the c...

Study of the X-ray radiation interaction with a multislit collimator for the creation of microbeams in radiation therapy

“…In the past decades, a large body of pre-clinical work has shown the potential and enhanced effectiveness of MRT compared with other conventional techniques based on homogeneous radiation fields (Laissue et al, 1998(Laissue et al, , 2013Schü ltke et al, 2008;Laissue et al, 2007Laissue et al, , 1992Van Der Sanden et al, 2010;Smyth et al, 2018;Bouchet et al, 2013Bouchet et al, , 2010Crosbie et al, 2010;Ibahim et al, 2016Ibahim et al, , 2014Fernandez-Palomo et al, 2020). Although MRT research initially focused on applications for cancer treatment, recent studies extend to the treatment of chronic pain and epilepsies (Zippo et al, 2019;Studer et al, 2015;Pouyatos et al, 2016Pouyatos et al, , 2013Anschel et al, 2011).…”