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Hypoxia inducible factor‐1 α inhibition produced anti‐allodynia effect and suppressed inflammatory cytokine production in early stage of mouse complex regional pain syndrome model
Author(s) -
Hsiao HungTsung,
Lin YaChi,
Wang Jeffrey ChiFei,
Tsai YuChuan,
Liu YenChin
Publication year - 2016
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12536
Subject(s) - allodynia , cytokine , hypoxia (environmental) , ischemia , sensitization , medicine , pathogenesis , microcirculation , pharmacology , nociception , anesthesia , inflammation , endocrinology , immunology , chemistry , hyperalgesia , receptor , oxygen , organic chemistry
Summary 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‐1 α ( HIF ‐1 α ) 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 ‐1 α , 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. CD 1 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‐1 β ( IL ‐1 β ) and HIF ‐1 α 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 ‐1 α but also decreased the expression of IL ‐1 β 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 ‐1 α may produce an analgesic effect and the associated suppression of inflammatory cytokine IL ‐1 β in a CPIP model.