Issn Print: 0265-0215

Publication Date: 2010/06/12


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Reactive oxygen species dependent increased spinal phosphorylations of ERK and JNK in hind paw ischemia/reperfusion injury-induced mechanical allodynia: 14AP10–10

D. G. Lim; K. H. Kwak; K. Y. Jung; J. S. Chang; W. Baek

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Background and Goal of Study: Reactive oxygen species (ROS) and inflammatory responses contribute to development of neuropathic pain.(1) Mitogen-activated protein kinases (MAPKs) are important for intracellular signal transduction and play critical roles in regulating neural plasticity and inflammatory responses. A neuropathic pain syndrome was produced in rats following prolonged hind paw ischemia/reperfusion (chronic post-ischemia pain: CPIP), creating an animal model of complex regional pain syndrome-Type I.(2) This study was designed to evaluate the effects of ROS on the activation of MAPKs in spinal cord. Herein we show superoxide and NO dependent phosphorylation of ERK and JNK in neuropathic pain model.
Materials and Methods: CPIP was produced by a Nitrile 70 Durometer O-ring for 3 hrs ischemia and subsequent reperfusion of left hind paw of SD rats. Changes of lipid peroxidation of spinal cord with allopurinol (40 mg/kg), an inhibitor of xanthine oxidase (XO), were measured to confirm increased XO-mediated ROS production in CPIP rat. To block the effects of ROS, allopurinol (LA: 4 mg/kg, HA: 40 mg/kg), superoxide dismutase (SOD, 4000 U/kg), N-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), or SOD ± L-NAME was treated (i.p.) for 3 days after reperfusion. Mechanical allodynia (MA) was measured for 1 week. The activations of MAPKs (ERK, p38, and JNK) in lumbar spinal cord in accordance with the changes of MA at 3 days after reperfusion (the lowest withdrawal threshold on von Frey stimulation) were analyzed by the Western blot. Data were expressed as the mean + SEM. Statistical analysis was performed using analysis of variance, followed by a post hoc Student-Newman-Keuls test (p < 0.05).
Results and Discussion: In all treated groups except vehicle group (CPIP), MA was attenuated at 3 days after reperfusion, which persisted for at least 1 week. Regardless of presence of L-NAME, SOD attenuated MA more significantly than L-NAME. The phophorylations of MAPKs are increased in vehicle group compared to other groups. The changes of ERK and JNK, not for p38, were correlated with ROS blockade and changes of MA.
Conclusion(s): This study suggests that ROS, especially superoxide or nitric oxide, are partly responsible for the development of MA via phosphorylations of ERK and JNK. The activation of p38 for MA is a non-ROS-dependent manner.
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