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    Analysis of the antinociceptive effect of systemic administration of tramadol and dexmedetomidine combination on rat models of acute and neuropathic pain
    (Pergamon-Elsevier Science Ltd, 2007) Guneli, Ensari; Yavasoglu, N. Ulkue Karabay; Apaydin, Sebnem; Uyar, Meltem; Uyar, Mehmet
    The aim of the present study was to investigate the possible antinociceptive effect of systemic administration of tramadol and dexmedetomidine either alone or in combination on acute and neuropathic pain models in rats. The antinociceptive effects of intraperitoneal (i.p.) tramadol (520 mg/kg) and dexmedetomidine (5-20 mu g/kg) and three different combinations of tramadol+dexmedetomidine (5 + 5, 5 + 10 and 10+ 5, mg/kg+ mu g/kg, respectively) were measured by tail-flick and hot-plate methods in acute pain. The effects on the sciatic nerve ligation-induced neuropathic pain was tested by i.p. administration of tramadol (5 mu g/kg), dexmedetomidine (5 mu g/kg) and tramadol + dexmedetomidine combination (5 + 5) using a thermal plantar test. Sedation/motor-incoordination was assessed on rotarod. Tramadol and dexmedetomidine produced dose-related antinociception in tail-flick and hot-plate tests. In both tests, combination of these drugs produced an antinociceptive effect that is greater than that produced by tramadol. or dexmedetomidine alone at several time points. In hot-plate test, tramadol + dexmedetomidine combination (5 + 10) exerted the strongest antinociceptive effect, while tramadol + dexmedetomidine combination (10 + 5) was significantly most effective in tail-flick test. In the neuropathic pain, the antinociceptive effect exerted by tramadol + dexmedetomidine combination (5 + 5) was also significantly greater than their applications alone. In rotarod test, tramadol (30 and 40 mg/kg), dexmedetomidine (30 and 40 mu g/kg), tramadol+dexmedetomidine combination (10+10, 20+20) produced sedation/motor-incoordination, whereas tramadol (5-20 mg/kg), dexmedetomidine (5-20 mu g/kg) and tramadol + dexmedetomidine combination (5 + 5, 5 + 10 and 10 + 5) did not produce any effect on sedation/motor-incoordination. The combination of tramadol and dexmedetomidine was more effective in increasing the pain threshold in acute and neuropathic pain when compared with the administration of either of these drugs alone. (C) 2007 Elsevier Inc. All rights reserved.
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    Effects of repeated administered ghrelin on chronic constriction injury of the sciatic nerve in rats
    (Elsevier Ireland Ltd, 2010) Guneli, Ensari; Onal, Aytul; Ates, Mehmet; Bagriyanik, Huesnue Alper; Resmi, Halil; Orhan, Cahide Elif; Kolatan, Hatice Efsun; Gumustekin, Mukaddes
    Chronic constriction injury (CCI) is a peripheral mononeuropathic pain model that is caused by an injury to the peripheral nervous system and refractory to available conventional treatment. Mechanisms involved in neuropathic pain are still unclear. Previous studies reveal that proinflammatory cytokines contribute to CC-induced peripheral nerve pathology. Ghrelin, a novel identified gastric peptide, has been shown to have antinociceptive activity and also anti-inflammatory properties by decreasing proinflammatory cytokines. Therefore, the aim of the present study was to investigate the effects of ghrelin on the CCI and its relationship with proinflammatory cytokines in rats. Wistar rats underwent sciatic nerve ligation to induce CCI fallowed by repeated ghrelin administrations (50 and 100 mu g/kg i.p., once daily) for a period of 14 days. Mechanical hyperalgesia was assessed before surgery and at day 14 after CCI. TNF-alpha, IL-1 beta and IL-6 were measured in blood and spinal cord. The changes of sciatic nerve was assessed histologically by both light and electron microscopy. Ghrelin attenuated mechanical hyperalgesia, reduced spinal TNF-alpha and IL-1 beta levels and enhanced sciatic nerve injury with correlated morphometric recovery. These results indicate that the protective effect by ghrelin in the spinal cord is mediated through the suppression of TNF-alpha and IL-1 beta. Thus ghrelin may be a promising peptide in the management of neuropathic pain. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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    Vagus nerve bundle stimulation using 1505-nm laser irradiation in an in-vivo rat model
    (Wiley-V C H Verlag Gmbh, 2022) Yetis, Ozan; Guner, Ozge; Akkaya, Ibrahim; Guneli, Ensari; Bagriyanik, Alper; Tozburun, Serhat
    Laser nerve stimulation using near-infrared laser irradiation has recently been studied in the peripheral nervous system as an alternative method to conventional electrical nerve stimulation. Bringing this method to the vagus nerve model could leverage this emerging stimulation approach to be tested in broader preclinical applications. Here, we report the capability of the laser nerve stimulation method on the rat vagus nerve bundle with a 1505-nm diode laser operated in continuous-wave mode. Studies of the stimulation threshold and laser-induced acute thermal injury to the nerve bundle were also performed to determine a temperature window for safe, reliable and reproducible laser stimulation of the rat vagus nerve bundle. The results show that laser stimulation of the vagus nerve bundle provides reliable and reproducible nerve stimulation in a rat model. These results also confirm a threshold temperature of >42 degrees C with acute nerve damage observed above 46 degrees C. A strong correlation was obtained between the laser time required to raise the nerve temperature above the stimulation threshold and the mean arterial pressure response. Advantages of the method such as non-contact delivery of external stimulus signals at mm scaled distance in air, enhanced spatial selectivity and electrical artefact-free measurements may indicate its potential to counteract the side effects of conventional electrical vagus nerve stimulation.