Potentiation of Spinal Glutamatergic Response in the Neuron-glia Interactions Underlies the Intrathecal IL-1β-induced Thermal Hyperalgesia in Rats

Overview

Journal CNS Neurosci Ther

Specialties Neurology
Pharmacology

Date 2017 May 26

PMID 28544775

Citations 9

Authors

Chun-Sung Sung

Zhi-Hong Wen

Chien-Wei Feng

Chun-Hong Chen

Shi-Ying Huang

Nan-Fu Chen

Wu-Fu Chen

Chih-Shung Wong

Affiliations

Soon will be listed here.

Abstract

Aims: We previously demonstrated that intrathecal IL-1β upregulated phosphorylation of p38 mitogen-activated protein kinase (P-p38 MAPK) and inducible nitric oxide synthase (iNOS) in microglia and astrocytes in spinal cord, increased nitric oxide (NO) release into cerebrospinal fluid, and induced thermal hyperalgesia in rats. This study investigated the role of spinal glutamatergic response in intrathecal IL-1β-induced nociception in rats.

Methods: The pretreatment effects of MK-801 (5 μg), minocycline (20 μg), and SB203580 (5 μg) on intrathecal IL-1β (100 ng) in rats were measured by behavior, Western blotting, CSF analysis, and immunofluorescence studies.

Results: IL-1β increased phosphorylation of NR-1 (p-NR1) subunit of N-methyl-D-aspartate receptors in neurons and microglia, reduced glutamate transporters (GTs; glutamate/aspartate transporter by 60.9%, glutamate transporter-1 by 55.0%, excitatory amino acid carrier-1 by 39.8%; P<.05 for all), and increased glutamate (29%-133% increase from 1.5 to 12 hours; P<.05) and NO (44%-101% increase from 4 to 12 hours; P<.05) levels in cerebrospinal fluid. MK-801 significantly inhibited all the IL-1β-induced responses; however, minocycline and SB203580 blocked the IL-1β-downregulated GTs and elevated glutamate but not the upregulated p-NR1.

Conclusion: The enhanced glutamatergic response and neuron-glia interaction potentiate the intrathecal IL-1β-activated P-p38/iNOS/NO signaling and thermal hyperalgesia.

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