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Papers of the Week


Papers: 20 May 2023 - 26 May 2023

RESEARCH TYPE:
Basic Science


Animal Studies, Molecular/Cellular, Neurobiology


2023 May 19


Sci Adv


37205760


9


20

Editor's Pick

Nociceptor activity induces nonionotropic NMDA receptor signaling to enable spinal reconsolidation and reverse pathological pain.

Authors

Zhang H, Rodriguez-Hernandez LD, D'Souza AJ, He D, Zain M, Fung SW, Bennett LA, Bonin RP

Abstract

Chronic, pathological pain is a highly debilitating condition that can arise and be maintained through central sensitization. Central sensitization shares mechanistic and phenotypic parallels with memory formation. In a sensory model of memory reconsolidation, plastic changes underlying pain hypersensitivity can be dynamically regulated and reversed following the reactivation of sensitized sensory pathways. However, the mechanisms by which synaptic reactivation induces destabilization of the spinal “pain engram” are unclear. We identified nonionotropic -methyl-d-aspartate receptor (NI-NMDAR) signaling as necessary and sufficient for the reactive destabilization of dorsal horn long-term potentiation and the reversal of mechanical sensitization associated with central sensitization. NI-NMDAR signaling engaged directly or through the reactivation of sensitized sensory networks was associated with the degradation of excitatory postsynaptic proteins. Our findings identify NI-NMDAR signaling as a putative synaptic mechanism by which engrams are destabilized in reconsolidation and as a potential means of treating underlying causes of chronic pain.