Superoxide and Nitric Oxide Involvement in Enhancing of N-methyl-D-aspartate Receptor-Mediated Central Sensitization in the Chronic Post-ischemia Pain Model

BACKGROUND: Recent studies indicate that reactive oxygen species (ROS) are involved in persistent pain, including neuropathic and inflammatory pain. Since the data suggest that ROS are involved in central sensitization, the present study examines the levels of activated N-methyl-D-aspartate (NMDA) receptors in the dorsal horn after an exogenous supply of three antioxidants in rats with chronic post-ischemia pain (CPIP). This serves as an animal model of complex regional pain syndrome type-I induced by hindpaw ischemia/reperfusion injury. METHODS: The application of tight-fitting O-rings for a period of three hours produced CPIP in male Sprague-Dawley rats. Allopurinol 4 mg/kg, allopurinol 40 mg/kg, superoxide dismutase (SOD) 4,000 U/kg, N-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg and SOD 4,000 U/kg plus L-NAME 10 mg/kg were administered intraperitoneally just after O-ring application and on the first and second days after reperfusion. Mechanical allodynia was measured, and activation of the NMDA receptor subunit 1 (pNR1) of the lumbar spinal cord (L4-L6) was analyzed by the Western blot three days after reperfusion. RESULTS: Allopurinol reduced mechanical allodynia and attenuated the enhancement of spinal pNR1 expression in CPIP rats. SOD and L-NAME also blocked spinal pNR1 in accordance with the reduced mechanical allodynia in rats with CPIP. CONCLUSION: The present data suggest the contribution of superoxide, produced via xanthine oxidase, and the participation of superoxide and nitric oxide as a precursor of peroxynitrite in NMDA mediated central sensitization. Finally, the findings support a therapeutic potential for the manipulation of superoxide and nitric oxide in ischemia/reperfusion related pain conditions.

Contralateral allodynia and central change in the chronic post-ischemic pain model rats / 대한마취과학회지

BACKGROUND: Mirror-image allodynia is a mysterious phenomenon that occurs in association with many clinical pain syndromes including complex regional pain syndromes (CRPS). Underlying mechanisms for the development of such pain are still a matter of investigation. Several studies suggest that activation of the N-methyl-D-aspartate (NMDA) receptor is essential for central sensitization as a base for persistent pain. The aim is to assess whether alteration of NMDA receptor expression correlates with the contralateral allodynia in the chronic post-ischemia pain (CPIP) model rats representing CRPS-Type I. METHODS: Application of a tight-fitting tourniquet for a period of 3 hours before reperfusion produced CPIP in male Sprague-Dawley rats. The mechanical paw withdrawal thresholds to von Frey stimuli (using a dynamic plantar aesthesiometer) were measured as pain indicators in ipsilateral and contralateral hindpaws. Phosphorylation of the NMDA receptor 1 subunit (pNR1), assessed with Western blot, was measured in the contralateral L4-6 spinal cord. RESULTS: Ipsilateral and contralateral mechanical allodynia is present at 4 hours after reperfusion, peaked at 3 days, and continued for 7 days after reperfusion. The relative density of pNR1 of CPIP rats significantly decreased in the contralateral L4-6 spinal cord compared to baseline value (P < 0.05). There was significant correlation between paw withdrawal threshold and the relative density of pNR1 (ipsilateral; R2 = 0.75, P < 0.01, contralateral; R2 = 0.60, P < 0.01). CONCLUSIONS: These data suggest that pNR1 is correlated to the contralateral mechanical allodynia in CPIP rats.

Reactive oxygen species and N-methyl-D-aspartate receptor-mediated central sensitization in hindlimb ischemia/reperfusion injury-induced neuropathic pain rats / 대한마취과학회지

BACKGROUND: Reactive oxygen species (ROS) contribute to development of neuropathic pain. A neuropathic pain syndrome was produced in rats following prolonged hindpaw ischemia/reperfusion injury, creating an animal model of complex regional pain syndrome-Type I (CRPS-I). This study was designed to evaluate the validity of this model for ROS and pain research. Herein we show superoxide produces N-methyl-D-aspartate (NMDA) mediated mechanical allodynia. METHODS: Male adult SD rats were used for neuropathic pain model. Plasma superoxide production rates of before ischemia (BI) and 5 min after reperfusion (JR) were measured via cytochrome C reduction in the presence of xanthine (without xanthine oxidase, kinetics, 550 nm). Mechanical allodynia was measured in both hindpaws. Activation of NMDA receptor subunit 1 (P-NR1) of lumbar spinal cord (L4-L6) in accordance with the change of allodynia was analyzed by the Western blot. RESULTS: Allopurinol-inhibitable, xanthine oxidase-mediated plasma superoxide production was increased at AR. Mechanical allodynia was present in both hindpaws as early as 1 hr after reperfusion, and lasted at least 1 week. The expression of P-NR1 was the highest at 3 days after reperfusion when the withdrawal threshold was the lowest point. SOD significantly blocked P-NR1 activation. CONCLUSIONS: This study suggests that ischemia/reperfusion injury induced neuropathic pain model is a good candidate for the research fields of ROS and pain mechanism. The generation of ROS, especially superoxide is partly responsible for NMDA-mediated mechanical allodynia.

Prognostic Value of PCNA , c-erbB-2 , c-fos in Patients with Non-small Cell Lung Cancer / 대한암학회지

PURPOSE: Oncogenes, tumor suppressor genes, and growth variables of tumors are important in the assessment of prognosis in lung cancer. The expression of PCNA, c-erbB-2 (HER-2/neu), and c-fos oncoprotein and their prognostic implications in surgically resected patients with non-small cell lung cancer were evaluated. MATERIALS AND METHODS: Seventy patients with non-small cell lung cancer were included and PCNA, c-erbB-2 and c-fos overexpression were evaluated by immunohistochemical stain using paraffin-embedded tissue. RESULTS: The mean proportion of PCNA positive cells was 18.6%, and there was no significant difference according to cell type and stage. The median survival time was significantly shorter in the group with high PCNA expression (>10%) as compared with the group with low PCNA expression (<10%) (37 months vs 16 months). Four (6.3%) of 64 cases demonstrated c-erbB-2 positivity. These were all adenocarcinoma cases. c-fos protein was only rarely overexpressed (1/51). CONCLUSION: PCNA expression was shown to be a useful prognostic parameter in resected non-small cell lung cancer while c-erbB-2 and c-fos oncoprotein were infrequently expressed.

A Pancreatic Cyst of the Anterior Mediastinum

Although heterotopia of pancreatic tissue is a developmental anomaly found in approximately 2% of all autopsies, pancreatic tissue within the thorax and mediastinum is uncommon. In most of these instances, the pancreatic tissue is a component of gastroenteric duplication cysts, intralobar pulmonary sequestrations or teratomas. We describe an anterior mediastinal cyst consisting entirely of pancreatic tissue. A previously healthy 27-year-old woman was admitted due to chest pain during deep inspiration. The computed tomographic scan of the thorax showed a large cyst occupying the right anterior mediastinum. The excised multilocular cystic lesion measured 12 cm in maximum diameter and contained a brown, turbid fluid. The wall was fibrotic and showed a haphazard mixture of ducts and exocrine acini without islets. The histogenesis of this lesion is unclear.