Intravenous Administration of Triptonide Attenuates CFA-Induced Pain Hypersensitivity by Inhibiting DRG AKT Signaling Pathway in Mice.

BACKGROUND

Currently, medical treatment of inflammatory pain is limited by a lack of safe and effective therapies. Triptonide (TPN), a major component of . with low toxicity, has been shown to have good anti-inflammatory and neuroprotective effects. The present study aims to investigate the effects of TPN on chronic inflammatory pain.

MATERIALS AND METHODS

Inflammatory pain was induced by intraplantar injection of complete Freund's adjuvant (CFA). TPN's three different doses were intravenously administered to compare the analgesic efficacy: 0.1 mg/kg, 0.5 mg/kg, and 2.0 mg/kg. The foot swelling was quantitated by measuring paw volume. Mechanical allodynia and thermal hyperalgesia were assessed with von Frey filament testing and Hargreaves' test, respectively. Western blots, qRT-PCR and immunofluorescence tests were used to analyze the expression of pAKT, (), (), and (). Two AKT inhibitors, AKT inhibitor Ⅳ and MK-2206, were used to examine AKT's effects on pain behavior and cytokines expression.

RESULTS

Intravenous treatment with TPN attenuated CFA-induced paw edema, mechanical allodynia, and thermal hyperalgesia. Western blotting and immunofluorescence results showed that CFA induced AKT activation in the dorsal root ganglion (DRG) neurons. However, these effects were suppressed by treatment with TPN. Furthermore, TPN treatment inhibited CFA-induced increase of pro-inflammatory cytokines, including , , and . Consistent with the in vivo data, TPN inhibited LPS-induced Akt phosphorylation and inflammatory mediator production in ND7/23 cells. Finally, intrathecal treatment with AKT inhibitor Ⅳ or MK-2206, attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, and simultaneously decreased the mRNA expression of , , and in DRG.

CONCLUSION

These data indicate that TPN attenuates CFA-induced pain potentially via inhibiting AKT-mediated pro-inflammatory cytokines production in DRG. TPN may be used for the treatment of chronic inflammatory pain.