Enhancement by interleukin-1β of AMPA and NMDA receptor-mediated currents in adult rat spinal superficial dorsal horn neurons

Molecular Pain

Eiichi Kumamoto¹  Shi-Wen Luo²  Tsugumi Fujita¹  Chang-Yu Jiang¹  Tao Liu³ 

[1] Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan;Center for Laboratory Medicine, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China;Department of Pediatrics, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China

关键词: Pain;    Spinal dorsal horn;    Whole-cell patch-clamp;    Glutamate receptor;    IL-1ra;    IL-1β;   

Others  :  862543
DOI  :  10.1186/1744-8069-9-16

 received in 2013-02-01, accepted in 2013-03-14,  发布年份 2013

【 摘 要 】

Background

Proinflammatory cytokine interleukin-1β (IL-1β) released from spinal microglia plays an important role in the maintenance of acute and chronic pain states. However, the cellular basis of this action remains poorly understood. Using whole-cell patch-clamp recordings, we examined the action of IL-1β on AMPA- and NMDA-receptor-mediated currents recorded from substantia gelatinosa (SG) neurons of adult rat spinal cord slices which are key sites for regulating nociceptive transmission from the periphery.

Results

AMPA- and NMDA-induced currents were increased in peak amplitude by IL-1β in a manner different from each other in SG neurons. These facilitatory actions of IL-1β were abolished by IL-1 receptor (IL-1R) antagonist (IL-1ra), which by itself had no detectable effects on AMPA- and NMDA-induced currents. The AMPA- but not NMDA-induced current facilitated by IL-1β was recovered to control level 30 min after IL-1β washout and largely depressed in Na⁺-channel blocker tetrodotoxin-containing or nominally Ca²⁺-free Krebs solution. Minocycline, a microglia inhibitor, blocked the facilitatory effect of IL-1β on AMPA- but not NMDA-induced currents, where minocycline itself depressed NMDA- but had not any effects on AMPA-induced currents.

Conclusions

IL-1β enhances AMPA and NMDA responses in SG neurons through IL-1R activation; the former but not latter action is reversible and due to an increase in neuronal activity in a manner dependent on extracellular Ca²⁺ and minocycline. It is suggested that AMPA and NMDA receptors are positively modulated by IL-1β in a manner different from each other; the former but not latter is mediated by a neurotransmitter released as a result of an increase in neuronal activity. Since IL-1β contributes to nociceptive behavior induced by peripheral nerve or tissue injury, the present findings also reveal an important cellular link between neuronal and glial cells in the spinal dorsal horn.

【 授权许可】

   
2013 Liu et al.; licensee BioMed Central Ltd.

【 图 表 】

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