Acute Morphine Activates Satellite Glial Cells and Up-Regulates IL-1β in Dorsal Root Ganglia in Mice via Matrix Metalloprotease-9

• Published in: Molecular pain 2012-03, Vol.8 (1), p.18-18
• Main Authors: Berta, Temugin, Liu, Tong, Liu, Yen-Chin, Xu, Zhen-Zhong, Ji, Ru-Rong
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Blotting, Western; Ganglia, Spinal - drug effects; Ganglia, Spinal - metabolism; Immunohistochemistry; Interleukin-1beta - metabolism; Male; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Mice; Mice, Knockout; Morphine - pharmacology; Neuroglia - drug effects; Neuroglia - metabolism; Real-Time Polymerase Chain Reaction
• ISSN: 1744-8069; 1744-8069
• DOI: 10.1186/1744-8069-8-18

Background: Activation of spinal cord glial cells such as microglia and astrocytes has been shown to regulate chronic opioid-induced antinociceptive tolerance and hyperalgesia, due to spinal up-regulation of the proinflammatory cytokines such as interleukin-1 beta (IL-1β). Matrix metalloprotease-9 (MMP-9) has been implicated in IL-1β activation in neuropathic pain. However, it is unclear whether acute opioid treatment can activate glial cells in the peripheral nervous system. We examined acute morphine-induced activation of satellite glial cells (SGCs) and up-regulation of IL-1β in dorsal root ganglia (DRGs), and further investigated the involvement of MMP-9 in these opioid-induced peripheral changes. Results: 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 pretreatment. Finally, intrathecal injections of IL-1β-selective siRNA not only reduced DRG IL-1β expression but also prolonged acute morphine-induced analgesia. Conclusions: 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 neuronglial interactions. Targeting peripheral glial activation might prolong acute opioid analgesia.