title: 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.
abstract: 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.
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanangno, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Salman
authors.initials: S
authors.lastname: Khan
authors.forename: Omer
authors.initials: O
authors.lastname: Shehzad
authors.forename: Jaemoo
authors.initials: J
authors.lastname: Chun
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000208:Acute Disease; D000255:Adenosine Triphosphate / Q000097:blood; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002908:Chronic Disease; D003374:Coumarins / Q000494:pharmacology* / Q000627:therapeutic use; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006930:Hyperalgesia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000150:complications; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010146:Pain / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D013373:Substance P / Q000097:blood; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000700:Analgesics; D003374:Coumarins; D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; C065837:anomalin; D000255:Adenosine Triphosphate; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases
keywords: Allodynia; Anomalin; CREB; Hyperalgesia; MAPK; NF-κB