The enhanced release of inflammatory
cytokines mediated by high mobility group box1 (
HMGB1) leads to
pain sensation, and has been implicated in the etiology of inflammatory
pain.
Paeonol (PAE), a major active phenolic component in Cortex Moutan, provides neuroprotective efficacy via exerting anti-inflammatory effect. However, the role and mechanism of PAE in inflammatory
pain remain to be fully clarified. In this study, we showed that PAE treatment significantly ameliorated mechanical and
thermal hyperalgesia of mice induced by complete
Freund's adjuvant (CFA). The
analgesic effect of PAE administration was associated with suppressing the enhanced expression of
HMGB1 as well as the downstream signaling molecules including
toll-like receptor 4 (TLR4), the nuclear NF-κB p65, TNF-α and IL-1β after CFA insult in the anterior cingulate cortex (ACC), a key brain region responsible for
pain processing. Furthermore, inhibition of
HMGB1 activity by
glycyrrhizin (GLY), an
HMGB1 inhibitor, alleviated CFA-induced
pain and also facilitated PAE-mediated
analgesic effect in mice along with the decreased expression of TLR4, NF-κB p65, TNF-α and IL-1β upon CFA injury. Collectively, we showed PAE exerted
analgesic effect through inhibiting the
HMGB1/TLR4/NF-κB p65 pathway and subsequent generation of
cytokines TNF-α and IL-1β in the ACC.