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Papers of the Week

Papers: 15 Jul 2023 - 21 Jul 2023

Basic Science

Animal Studies, Neurobiology

Musculoskeletal Pain, Neuropathic Pain

2023 Jul 12



Emergent epileptiform activity drives spinal sensory circuits to generate ectopic bursting in intraspinal afferent axons after cord injury.


Bryson M, Kloefkorn H, Idlett-Ali S, Martin K, Garraway SM, Hochman S


Spinal cord injury ( ) leads to hyperexcitability and dysfunction in spinal sensory processing. As hyperexcitable circuits can become epileptiform elsewhere, we explored whether such activity emerges in spinal sensory circuits in a thoracic SCI contusion model of neuropathic pain. Recordings from spinal sensory axons in multiple below-lesion segmental dorsal roots ( ) demonstrated that SCI facilitated the emergence of spontaneous ectopic burst spiking in afferent axons, which synchronized across multiple adjacent DRs. Burst frequency correlated with behavioral mechanosensitivity. The same bursting events were recruited by afferent stimulation, and timing interactions with ongoing spontaneous bursts revealed that recruitment was limited by a prolonged post-burst refractory period. Ectopic bursting in afferent axons was driven by GABA receptor activation, presumably via shifting subthreshold GABAergic interneuronal presynaptic axoaxonic inhibitory actions to suprathreshold spiking. Collectively, the emergence of stereotyped bursting circuitry with hypersynchrony, sensory input activation, post-burst refractory period, and reorganization of connectivity represent defining features of epileptiform networks. Indeed, these same features were reproduced in naïve animals with the convulsant 4-aminopyridine ( ). We conclude that SCI promotes the emergence of epileptiform activity in spinal sensory networks that promotes profound corruption of sensory signaling. This corruption includes downstream actions driven by ectopic afferent bursts that propagate via reentrant central and peripheral projections and GABAergic presynaptic circuit hypoexcitability during the refractory period.