Ionotropic Glutamate Receptors and Voltage-Gated Ca²⁺Channels in Long-Term Potentiation of Spinal Dorsal Horn Synapses and Pain Hypersensitivity

Abstract

Over the last twenty years of research on cellular mechanisms of pain hypersensitivity, long-term potentiation (LTP) of synaptic transmission in the spinal cord dorsal horn (DH) has emerged as an important contributor to pain pathology. Mechanisms that underlie LTP of spinal DH neurons include changes in the numbers, activity, and properties of ionotropic glutamate receptors (AMPA and NMDA receptors) and of voltage-gated Ca2+ channels. Here, we review the roles and mechanisms of these channels in the induction and expression of spinal DH LTP, and we present this within the framework of the anatomical organization and synaptic circuitry of the spinal DH. Moreover, we compare synaptic plasticity in the spinal DH with classical LTP described for hippocampal synapses.

Sequential Activation of AMPA Receptors and Glial Cells in a Pain Model of Lumbar Spine Disc Herniation

“…Functional AMPA receptors have been observed in various brain regions and the spinal cord. AMPA receptors are ionotropic glutamate receptors in the post-synaptic membrane that dynamically respond to nociceptive input from peripheral inflammation and contribute to the maintenance of long-lasting transmission of somatosensory input [ 20 , 21 ]. AMPA receptor phosphorylation and upregulation of AMPA increase permeability to Na + and Ca 2+ , which increases EPSCs [ 4 , 22 ].…”

Regulation of Nociceptive Plasticity Threshold and DARPP-32 Phosphorylation in Spinal Dorsal Horn Neurons by Convergent Dopamine and Glutamate Inputs

“…Glutamate-dependent plasticity associated to spinal hyperexcitability in persistent pain states [ 53 , 54 ] involves enhanced activation of the NMDA receptor [ 29 , 13 ], presumably due to receptor permeation [ 55 ] or phosphorylation of specific subunits [ 56 , 57 ]. Switching the NMDA receptor to a high activation state in dorsal horn neurons is commonly assumed to be achieved by intense noxious input or conditioning high-frequency afferent stimulation [ 37 , 49 , 58 , 59 , 60 , 61 ]. In basal conditions, low-frequency stimulation in vivo either only inconsistently leads to LTP [ 39 ] or fails to do so as found here.…”

Correction of disorders of neuronal homeostatic mechanisms in case of neuropsychiatric diseases as a probable direction of drug exposure

“…В основе центральной сенситизации лежит развитие ДП синаптической потенциации в синапсах головного и спинного мозга. В спинном мозге, преимущественно в задних рогах, ДП обусловлена повышением плотности постсинаптических AMPA-и NMDA-глутаматных рецепторов и п/з каналов Са 2+ [57]. В синапсах нейронов 2/3 слоев ППК в условиях нейропатической боли наблюдали повышение плотности содержащих GluA1 субъединицу AMPA-глутаматных рецепторов и усиление пресинаптического высвобождение глутамата [54].…”