Loss of Ca(2+)-permeable AMPA receptors in synapses of tonic firing substantia gelatinosa neurons in the chronic constriction injury model of neuropathic pain.

Loss of Ca(2+)-permeable AMPA receptors in synapses of tonic firing substantia gelatinosa neurons in the chronic constriction injury model of neuropathic pain. Exp Neurol. 2016 Mar 3; Authors: Chen Y, Derkach VA, Smith PA Abstract Synapses transmitting nociceptive information in the spinal dorsal horn undergo enduring changes following peripheral nerve injury. Indeed, such injury alters the expression of the GluA2 subunit of glutamatergic AMPA receptors (AMPARs) in the substantia gelatinosa and this predicts altered channel conductance and calcium permeability, leading to an altered function of excitatory synapses. We therefore investigated the functional properties of synaptic AMPA receptors in rat substantia gelatinosa neurons following 10-20d chronic constriction injury (CCI) of the sciatic nerve; a model of neuropathic pain. We measured their single-channel conductance and sensitivity to a blocker of calcium permeable AMPA receptors (CP-AMPARs), IEM1460 (50μM). In putative inhibitory, tonic firing neurons, CCI reduced the average single-channel conductance of synaptic AMPAR from 14.4±3.5pS (n=12) to 9.2±1.0pS (n=10, p<0.05). IEM1460 also more effectively antagonized evoked, spontaneous and miniature EPSCs in tonic neurons from sham operated animals than in those from animals that had been subjected to CCI. By contrast, CCI did not change the effectiveness of IEM1460 in delay firing neurons although average single channel co...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research