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Authors & Affiliations
Marilou Lentschat, Anissa Hezzam, Pierre Hener, Ipek Yalcin, Pierre Veinante
Abstract
Chronic pain is a major public health issue, often accompanied by comorbidities such as anxiety and depression. Thanks to the work of our team, we now know that the development of these disorders are linked to a dysregulation of the excitatory/inhibitory (EI) balance in cortical structures, such as the anterior cingulate cortex (ACC) and basolateral amygdala (BLA). An essential actor for the EI balance are the fast-spiking interneurons expressing parvalbumin (INPV). These neurons are surrounded by a specialized extracellular matrix, the perineuronal nets (PNNs) which regulate their functions and plasticity. PNNs have been showed to be dysregulated in both chronic pain and depression, but their potential role in anxiety and depression induced by chronic pain has yet to be investigated. Here, we analyzed PNNs and INPV alterations in a mouse model of neuropathic pain induced anxiodepressive-like behaviors. We implanted mice with a polyethylene cuff around the right sciatic nerve and assessed mechanical allodynia and the development of anxiodepressive-like symptoms using behavioral tests at different time points post-surgery. INPV and PNNs were labelled by immunofluorescence and histofluorescence, respectively. Their number and intensity were analyzed and quantified in the ACC and the BLA using Stardist and Cellpose. Our results suggest that INPV and PNNs are not altered in neuropathic mice before the development of anxiodepressive-like behaviors, 2 weeks post-surgery, whereas PNNs seem to be altered in neuropathic mice presenting anxiodepressive-like behaviors, 8 weeks after the surgery. These results suggest a role of PNNs in the development of chronic pain anxiodepressive comorbidities.