PPARα Agonist WY-14643 Relieves Neuropathic Pain through SIRT1-Mediated Deacetylation of NF-κB

Abstract

Inflammation caused by neuropathy contributes to the development of neuropathic pain (NP), but the exact mechanism still needs to be understood. Peroxisome proliferator-activated receptor <i>α</i> (PPAR<i>α</i>), an important inflammation regulator, might participate in the inflammation in NP. To explore the role of PPAR<i>α</i> in NP, the effects of PPAR<i>α</i> agonist WY-14643 on chronic constriction injury (CCI) rats were evaluated. The results showed that WY-14643 stimulation could decrease inflammation and relieve neuropathic pain, which was relative with the activation of PPAR<i>α</i>. In addition, we also found that the SIRT1/NF-<i>κ</i>B pathway was involved in the WY-14643-induced anti-inflammation in NP, and activation of PPAR<i>α</i> increased SIRT1 expression, thus reducing the proinflammatory function of NF-<i>κ</i>B. These data suggested that WY-14643 might serve as an inflammation mediator, which may be a potential therapy option for NP.