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Ht31 peptide inhibited inflammatory pain by blocking NMDA receptor-mediated nociceptive transmission in spinal dorsal horn of mice.
- Source :
-
Neuropharmacology [Neuropharmacology] 2015 Feb; Vol. 89, pp. 290-7. Date of Electronic Publication: 2014 Oct 12. - Publication Year :
- 2015
-
Abstract
- A kinase anchoring proteins (AKAPs) assemble cAMP-dependent protein kinase (PKA) into signaling complexes with a wide range of ion channels, including N-methyl-d-aspartate (NMDA)-subtype glutamate receptor (NMDAR) that is critical for the central sensitization of nociceptive behaviors. Although PKA has been widely described in the regulation of NMDAR-dependent nociceptive transmission and plasticity, the roles of AKAPs in these processes are largely unknown as yet. The present study interfered with AKAPs/PKA interaction by introducing stearated Ht31 peptide (St-Ht31) into spinal dorsal horn neurons, and investigated the possible changes of primary afferent-evoked, NMDAR-mediated excitatory postsynaptic currents (NMDAR-EPSCs). Whole-cell patch clamp recordings demonstrated that intracellular loading of St-Ht31 through the glass pipettes didn't affect NMDAR-mediated synaptic responses in the spinal cord slices from intact mice. When inflammatory pain was established by intraplantar injection of Complete Freund's Adjuvant (CFA), however, St-Ht31 significantly repressed the amplitudes of NMDAR-EPSCs by selectively removing GluN2B subunit-containing NMDAR out of synapses. With the inhibition of NMDAR-mediated nociceptive transmission, St-Ht31 effectively ameliorated CFA-induced inflammatory pain. Pharmacological manipulation of microtubule-based NMDAR transport, dynamin-dependent NMDAR endocytosis or actin depolymerization abolished the inhibitory effects of St-Ht31 peptide on NMDAR-EPSCs, suggesting that disruption of AKAPs/PKA interaction by St-Ht31 might disturb multiple NMDAR trafficking steps to reduce the receptor synaptic expression and spinal sensitization.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Subjects :
- Action Potentials drug effects
Animals
Disease Models, Animal
Freund's Adjuvant toxicity
In Vitro Techniques
Inflammation chemically induced
Inflammation complications
Male
Mice
Mice, Inbred Strains
Motor Activity drug effects
Neurons ultrastructure
Pain etiology
Pain Measurement
Pain Threshold drug effects
Spinal Cord pathology
Subcellular Fractions drug effects
Subcellular Fractions metabolism
Anesthetics therapeutic use
Ganglia, Spinal cytology
Neurons drug effects
Pain drug therapy
Proteins therapeutic use
Sensory Receptor Cells drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7064
- Volume :
- 89
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 25312281
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2014.09.031