N-acetyl-cysteine attenuates remifentanil-induced postoperative hyperalgesia via inhibiting matrix metalloproteinase-9 in dorsal root ganglia.

Abstract

Treatment of remifentanil-induced postoperative hyperalgesia (RIH) remains a clinical challenge because the mechanisms are not fully understood. Matrix metalloproteinase-9 (MMP-9) is a key component in neuroinflammation because of its facilitation of pro-inflammatory cytokine maturation. Therefore, inhibition of MMP-9 may represent a novel therapeutic approach to the treatment of RIH. Sprague-Dawley rats were randomly divided into three groups: Control, Incision and Remifentanil. A right plantar surgical incision was performed in Group Incision, and intraoperative remifentanil (0.04 mg/kg, 0.4 ml) was infused subcutaneously for 30 min in Group Remifentanil. The results indicated that intraoperative remifentanil induced an up-regulation and activation of MMP-9 in DRGs but not spinal cords. MMP-9 was expressed primarily in DRG neurons co-expressing mu opioid receptors (MOR), and elicited interleukin-1β (IL-1β) cleavage in DRG neurons and satellite glial cells (SGCs). Intraperitoneal injection of N-acetyl-cysteine (NAC), a broadly used safe drug, significantly attenuated RIH via suppressing the activation of MMP-9 in DRGs. NAC inhibited the cleavage of IL-1β in DRGs, which is a critical substrate of MMP-9, and markedly suppressed glial activation and neuron excitability in spinal dorsal horn induced by remifentanil. These results demonstrated that NAC can effectively alleviate RIH via powerfully inhibiting MMP-9 activation in DRGs.

• Authors: Yue Liu, Yuan Ni, Wei Zhang, Yu-E Sun, Zhengliang Ma, Xiaoping Gu
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 10 Pg. 16988-17001 (Mar 07 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28199982 (Publication Type: Journal Article)

Chemical References

• Analgesics, Opioid
• Free Radical Scavengers
• NR1 NMDA receptor
• NR2B NMDA receptor
• Piperidines
• Receptors, N-Methyl-D-Aspartate
• protein kinase C gamma
• Protein Kinase C
• Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 9
• Remifentanil
• Acetylcysteine

Topics

• Acetylcysteine (administration & dosage, pharmacology)
• Analgesics, Opioid (administration & dosage, toxicity)
• Animals
• Blotting, Western
• Enzyme Activation (drug effects)
• Free Radical Scavengers (administration & dosage, pharmacology)
• Ganglia, Spinal (drug effects, enzymology, metabolism)
• Hyperalgesia (chemically induced, prevention & control)
• Infusions, Subcutaneous
• Injections, Intraperitoneal
• Male
• Matrix Metalloproteinase 9 (metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Pain Measurement (methods)
• Phosphorylation (drug effects)
• Piperidines (administration & dosage, toxicity)
• Postoperative Period
• Protein Kinase C (metabolism)
• Rats, Sprague-Dawley
• Receptors, N-Methyl-D-Aspartate (metabolism)
• Remifentanil