Back

Sex specific axon initial segment plasticity underlies cortical hyperexcitability in trigeminal pain

Loudan, J.; Herault, K.; Damart, T.; Murail, P.; Michon, A.; Fraiah, S.; Gabrielli, F.; Moisset, X.; Dallel, R.; Zbili, M.

2025-10-13 neuroscience
10.1101/2025.10.11.681811 bioRxiv
Show abstract

Neuropathic pain results from peripheral lesion, causing maladaptive plasticity and central sensitization. Clinical and preclinical studies demonstrate that modifications of primary sensory cortex (S1) activity are essential for neuropathic pain persistence. Rodent studies report heightened S1 pyramidal cell excitability in neuropathic pain model, the origins of which remain debated. The axon initial segment, the action potential trigger zone, is a major determinant of neuronal excitability and is known to undergo structural changes after neural perturbation but its role in chronic pain is poorly understood and no studies have explored its role in cortical hyperexcitability in chronic pain models. Besides, despite a higher prevalence of chronic pain in women, most of preclinical studies have been conducted in males. By integrating electrophysiology, immunohistochemistry, and computational modeling, this study demonstrates that in a trigeminal neuropathic pain rat model, sex-specific structural plasticity of the axon initial segment enhances the excitability of layer 5 pyramidal cells in the somatosensory cortex, potentially driving network-level hyperactivity.

Matching journals

The top 7 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.