title: Hypoxia inducible factor-1α inhibition produced anti-allodynia effect and suppressed inflammatory cytokine production in early stage of mouse complex regional pain syndrome model.
abstract: Complex regional pain syndrome (CRPS) is related to microcirculation impairment associated with tissue hypoxia and peripheral cytokine overproduction in the affected limb. Previous studies suggest that the pathogenesis involves hypoxia inducible factor-1α (HIF-1α) and exaggerated regional inflammatory response. 1-methylpropyl 2-imidazolyl disulfide (PX-12) acts as the thioredoxin-1 (Trx-1) inhibitor and decreases the level of HIF-1α, and can rapidly be metabolized for Trx-1 redox inactivation. This study hypothesized that PX-12 can decrease the cytokine production for nociceptive sensitization in the hypoxia-induced pain model. CD1 mice weighing around 30 g were used. The animal CRPS model was developed via the chronic post-ischaemic pain (CPIP) model. The model was induced by using O-rings on the ankles of the mice hind limbs to produce 3-h ischaemia-reperfusion injury on the paw. PX-12 (25 mg/kg, 5 mg/kg) was given through tail vein injection immediately after ischaemia. Animal behaviour was tested using the von Frey method for 7 days. Local paw skin tissue was harvest from three groups (control, 5 mg/kg, 25 mg/kg) 2 h after injection of PX-12. The protein expression of interleukin-1β (IL-1β) and HIF-1α was analysed with the Western blotting method. Mice significantly present an anti-allodynia effect in a dose-related manner after the PX-12 administration. Furthermore, PX-12 not only decreased the expression of HIF-1α but also decreased the expression of IL-1β over the injured palm. This study, therefore, shows the first evidence of the anti-allodynia effect of PX-12 in a CPIP animal model for pain behaviour. The study concluded that inhibition of HIF-1α may produce an analgesic effect and the associated suppression of inflammatory cytokine IL-1β in a CPIP model.
authors.affiliation: Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.|Department of Anesthesiology, E-Da hospital, E-Da University, Kaohsiung City, Taiwan.
authors.forename: Hung-Tsung
authors.initials: HT
authors.lastname: Hsiao
authors.affiliation: Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
authors.forename: Ya-Chi
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
authors.forename: Jeffrey Chi-Fei
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Tsai
authors.affiliation: Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
authors.forename: Yen-Chin
authors.initials: YC
authors.lastname: Liu
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D020918:Complex Regional Pain Syndromes / Q000150:complications*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004220:Disulfides / Q000494:pharmacology* / Q000627:therapeutic use; D006930:Hyperalgesia / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000378:metabolism; D008297:Male; D051379:Mice
chemical_list: D016207:Cytokines; D004220:Disulfides; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007093:Imidazoles; C412893:1-methylpropyl-2-imidazolyl disulfide
keywords: PX-12; chronic post-ischaemic pain; complex regional pain syndrome; hypoxia inducible factor-1α; interleukin-1β