Potentiation of spinal glutamatergic response in the neuron-glia interactions underlies the intrathecal IL-1[beta]-induced thermal hyperalgesia in rats

Summary Aims We previously demonstrated that intrathecal IL-1[beta] 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-1[beta]-induced nociception in rats. Methods The pretreatment effects of MK-801 (5 µg), minocycline (20 µg), and SB203580 (5 µg) on intrathecal IL-1[beta] (100 ng) in rats were measured by behavior, Western blotting, CSF analysis, and immunofluorescence studies. Results IL-1[beta] 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