Mechanism underlying anti-hyperalgesic and anti-allodynic properties of anomalin in both acute and chronic inflammatory pain models in mice through inhibition of NF-κB, MAPKs and CREB signaling cascades.
The numerous mediators of pain and inflammation are products of injury-induced gene expression that lead to changes in the nervous system and immune responses. These multiple molecules and mechanisms suggest novel strategies that could be used for analgesic drug development. The present study investigated the possible anti-hyperalgesic effects of anomalin in complete Freund's adjuvant (CFA)-induced acute and chronic inflammatory pain models. Acute pretreatment of mice with anomalin (10 and 50mg/kg, i.p.) produced a significant anti-nociceptive effect against CFA- and carrageenan-induced mechanical hyperalgesia and allodynia. In a chronic pain model, administration of anomalin inhibited CFA-induced hyperalgesia, and it did not cause any apparent toxicity. Another set of experiments observed that anomalin inhibited CFA- and carrageenan-induced paw edema in acute and chronic models. To elucidate the molecular mechanism underlying the anti-nociceptive effect of anomalin, the various pain signaling pathways [NF-κB, cAMP response element-binding protein (CREB), and mitogen activated protein kinase (MAPKs)/AP-1] that are involved were examined. Intraperitoneal (i.p.) pretreatment of anomalin exhibited potent inhibitory effects on direct mediators of hyperalgesia (iNOS and COX-2). The release of CFA-induced plasma nitrite and paw tissue hyperalgesic cytokine (TNF-α) was reduced remarkably. In addition, the adenosine 5'-triphosphate (ATP) in plasma and substance P (SP) in paw tissue were markedly suppressed by anomalin. These results demonstrate that anomalin exhibits an analgesic effect in a consistent manner and that its mechanisms involve the inhibition of the NF-κB, CREB, and MAPKs/AP-1 signaling pathways.
['Khan|Salman|S|', 'Shehzad|Omer|O|', 'Chun|Jaemoo|J|', 'Kim|Yeong Shik|YS|']
D000208:Acute Disease D000255:Adenosine Triphosphate D000700:Analgesics D000818:Animals D002908:Chronic Disease D003374:Coumarins D017362:Cyclic AMP Response Element-Binding Protein D051546:Cyclooxygenase 2 D004195:Disease Models, Animal D015971:Gene Expression Regulation, Enzymologic D006930:Hyperalgesia D007249:Inflammation D008099:Liver D008297:Male D051379:Mice D020928:Mitogen-Activated Protein Kinases D016328:NF-kappa B D052247:Nitric Oxide Synthase Type II D009573:Nitrites D010146:Pain D015398:Signal Transduction D013373:Substance P D013997:Time Factors D014409:Tumor Necrosis Factor-alpha
Anomalin NF-κB MAPK CREB Hyperalgesia Allodynia