Open AccessPotentiation of spinal glutamatergic response in the neuron‐glia interactions underlies the intrathecal IL‐1β‐induced thermal hyperalgesia in rats
Author(s) -
Sung ChunSung,
Wen ZhiHong,
Feng ChienWei,
Chen ChunHong,
Huang ShiYing,
Chen NanFu,
Chen WuFu,
Wong ChihShung
Publication year - 2017
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12705
Subject(s) - glutamate receptor , glutamatergic , chemistry , pharmacology , nitric oxide synthase , microglia , nitric oxide , spinal cord , minocycline , medicine , receptor , neuroscience , biochemistry , biology , inflammation , organic chemistry , antibiotics
Summary 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 SB 203580 (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‐ NR 1) subunit of N ‐methyl‐D‐aspartate receptors in neurons and microglia, reduced glutamate transporters ( GT s; 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 SB 203580 blocked the IL ‐1β‐downregulated GT s and elevated glutamate but not the upregulated p‐ NR 1. Conclusion The enhanced glutamatergic response and neuron‐glia interaction potentiate the intrathecal IL ‐1β‐activated P‐p38/ iNOS / NO signaling and thermal hyperalgesia.