Anti-inflammatory effects of fentanyl and morphine on LPS-induced TLR4 neuroinflammatory signaling

  • Leandra Figueroa-Hall OSU-COM
  • Craig Stevens OSU-COM
  • Davis Randall OSU-COM
Keywords: opioids, neuroinflammation, TLR4, LPS, fentanyl, morphine


Opioid receptors located in the central nervous system and periphery are activated by opioids, which are classified as analgesics and non-analgesics. While investigations show opioids may have more severe consequences on inflammation and neuroinflammation due to down-regulation of cellular functions, these findings remain debatable. With these controversial implications at the forefront, we chose to investigate the fentanyl- and morphine-mediated effects on LPS-induced TLR4 neuroinflammatory signaling. CHME-5 microglial cells treated with LPS induced mu opioid receptor gene expression. Co-treatment with LPS and fentanyl or morphine significantly decreased LPS-induced IκBα activation, while only fentanyl decreased NF-κB binding activity. Furthermore, treatment with naltrexone did not reverse the fentanyl-mediated down-regulation of NF-κB binding activity. These findings indicate that fentanyl, and to a lesser extent morphine, display anti-inflammatory effects on LPS-induced TLR4 signaling.



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