Toll-like Receptor 4 Mediates Morphine-Induced Neuroinflammation and Tolerance via Soluble Tumor Necrosis Factor Signaling.

ABSTRACT: Opioid tolerance and the potential for addiction is a significant burden associated with pain management, yet its precise underlying mechanism and prevention remain elusive. Immune signaling contributes to the decreased efficacy of opioids, and we recently demonstrated that Toll-like receptor 4 (TLR4)-mediated neuroinflammation in the periaqueductal gray (PAG) drives tolerance. Tumor necrosis factor (TNF), a product of TLR4 signaling, promotes inflammation and facilitates glutamatergic signaling, key components of opioid tolerance. Therefore, we hypothesize that TLR4-mediated opioid tolerance requires TNF signaling. By expression of a dominant-negative TNF peptide via lentiviral vector injection in rat PAG to sequester soluble TNF (solTNF), we demonstrate that solTNF mediates morphine tole

SUBMITTER: Eidson LN 

PROVIDER: S-EPMC5240168 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature