Role of microglial activation on neuronal excitability in rat substantia gelatinosa
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Glial cells, including astrocytes and microglia, interact closely with neurons and modulate pain transmission,particularly under pathological conditions. In this study, we examined the excitability of substantia gelatinosa (SG)neurons of the spinal dorsal horn using a patch clamp recording to investigate the roles of microglial activation inthe nociceptive processes of rats. We used xanthine/xanthine oxidase (X/XO), a generator of superoxide anion (O2∙–),to induce a pathological pain condition. X/XO treatment induced an inward current and membrane depolarization. The inward current was significantly inhibited by minocycline, a microglial inhibitor, and fluorocitrate, an astrocyteinhibitor. To examine whether toll-like receptor 4 (TLR4) in microglia was involved in the inward current, we usedlipopolysaccharide (LPS), a highly specific TLR4 agonist. The LPS induced inward current, which was decreasedby pretreatment with Tak-242, a TLR4-specific inhibitor, and phenyl N-t-butylnitrone, a reactive oxygen speciesscavenger. The X/XO-induced inward current was also inhibited by pretreatment with Tak-242. These results indicatethat the X/XO-induced inward current of SG neurons occurs through activation of TLR4 in microglial cells, suggestingthat neuroglial cells modulate the nociceptive process through central sensitization.
Abstract
Glial cells, including astrocytes and microglia, interact closely with neurons and modulate pain transmission,particularly under pathological conditions. In this study, we examined the excitability of substantia gelatinosa (SG)neurons of the spinal dorsal horn using a patch clamp recording to investigate the roles of microglial activation inthe nociceptive processes of rats. We used xanthine/xanthine oxidase (X/XO), a generator of superoxide anion (O2∙–),to induce a pathological pain condition. X/XO treatment induced an inward current and membrane depolarization. The inward current was significantly inhibited by minocycline, a microglial inhibitor, and fluorocitrate, an astrocyteinhibitor. To examine whether toll-like receptor 4 (TLR4) in microglia was involved in the inward current, we usedlipopolysaccharide (LPS), a highly specific TLR4 agonist. The LPS induced inward current, which was decreasedby pretreatment with Tak-242, a TLR4-specific inhibitor, and phenyl N-t-butylnitrone, a reactive oxygen speciesscavenger. The X/XO-induced inward current was also inhibited by pretreatment with Tak-242. These results indicatethat the X/XO-induced inward current of SG neurons occurs through activation of TLR4 in microglial cells, suggestingthat neuroglial cells modulate the nociceptive process through central sensitization.
참고문헌 (39)
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