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Chronic Neuropathic Pain Induces Significant Neuronal Loss and Structural Alterations in the Secondary Motor Cortex

Amrita Das Gupta1, Hongwei Zheng1, Jennifer John1, Johannes Knabbe1, Thomas Kuner1

1 Department of Functional Neuroanatomy, Heidelberg University

Chronic neuropathic pain induces substantial structural plasticity in the brain, yet its impact at the mesoscopic scale of tissue composition remains elusive. This study delves into the cellular architecture and neuronal dynamics within cortical regions during chronic neuropathic pain progression. Employing longitudinal in vivo two-photon microscopy combined with behavioral assessments in a mouse model, we meticulously analyzed cortical volumes comprising approximately 25,000 cells and tracked individual neuronal changes post spared-nerve injury (SNI). Our findings reveal a pronounced neuronal loss in the secondary motor cortex (M2), situated adjacent to the cingulate cortex, emerging within just two weeks after injury. This research spotlights M2 as a critical region implicated in neuropathic pain and underscores neuronal loss as a vital and previously underrecognized mechanism contributing to the chronic pain state.