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Acute morphine activates satellite glial cells and up-regulates IL-1β in dorsal root ganglia in mice via matrix metalloprotease-9

DOI: 10.1186/1744-8069-8-18

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Subcutaneous morphine injection (10 mg/kg) induced robust peripheral glial responses, as evidenced by increased GFAP expression in DRGs but not in spinal cords. The acute morphine-induced GFAP expression is transient, peaking at 2 h and declining after 3 h. Acute morphine treatment also increased IL-1β immunoreactivity in SGCs and IL-1β activation in DRGs. MMP-9 and GFAP are expressed in DRG neurons and SGCs, respectively. Confocal analysis revealed a close proximity of MMP-9 and GFAP immunostaining. Importantly, morphine-induced DRG up-regulation of GFAP expression and IL-1β activation was abolished after Mmp9 deletion or naloxone pre-treatment. Finally, intrathecal injections of IL-1β-selective siRNA not only reduced DRG IL-1β expression but also prolonged acute morphine-induced analgesia.Acute morphine induces opioid receptors- and MMP-9-dependent up-regulation of GFAP expression and IL-1β activation in SGCs of DRGs. MMP-9 could mask and shorten morphine analgesia via peripheral neuron-glial interactions. Targeting peripheral glial activation might prolong acute opioid analgesia.Mounting evidence indicates that activation of spinal cord glial cells such as microglia and astrocytes plays a crucial role in the pathogenesis of chronic pain [1-7]. In particular, chronic opioid exposure induces profound changes in spinal cord microglia and astrocytes [8-10]. Upon activation spinal glial cells produce multiple proinflammatory cytokines such as TNF-α, IL-1β, and IL-6 to antagonize morphine analgesia and promote morphine tolerance [11-14], via sensitization of spinal cord dorsal horn neurons [15-17]. For example, IL-1β has been shown to counteract opioid-induced analgesia following both chronic and acute administration of morphine [18]. While intrathecal injection of the inteurleukin-1 receptor (IL-1R) antagonist potentiates acute morphine analgesia [11], intrathecal administration of IL-1β induces heat hyperalgesia [15]. Of interest genetic polymorphism of IL-1R antagon


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