Deneysel inflamatuvar ağrı modelinde CDP-kolinin analjezik etkisi ve etki mekanizması
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Date
2008
Authors
Bağdaş, Deniz
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Publisher
Uludağ Üniversitesi
Abstract
CDP-kolin, vücutta endojen üretilen nükleotid yapısında bir bileşik olup, sıçanlarda akut ağrı modellerinde analjezik etkisi gösterilmiştir. Çalışmada; deneysel inflamatuvar ağrı modelinde CDP-kolin’in, carrageenan uygulamasına bağlı gelişen hiperaljezi ve pençe ödemi üzerine etkisi araştırıldı; analjezik etkileri değerlendirildi. Deneylerde Sprague-Dawley erkek sıçanlar kullanıldı. İlaçlar, tuzlu su içinde hazırlanarak intraserebroventriküler yolla 10 µl hacimde uygulandı. İnflamasyon, sıçanların sağ arka pençelerine intraplantar % 2’lik λ-carrageenan enjeksiyonu (100 µl) yapılarak oluşturuldu. İnflamatuvar ağrı duyarlılığı termal ve mekanik pençe çekme testleriyle, carrageenana bağlı gelişen pençe ödeminde pençe genişliği dijital mikrometreyle ölçülerek değerlendirildi. CDP-kolin (0.5, 1 ve 2 µmol) her iki testte doza ve zamana bağlı olacak şekilde antihiperaljezik etki oluşturdu. Antihiperaljezik etki eşmolar dozlardaki (1 µmol) kolin ve CDP-kolin uygulamasında benzer şekilde ortaya çıkarken; sitidin için aynı etki termal pençe çekme testinde görülmeyip, mekanik pençe çekme testinde 5. dakikada saptandı. CDP-kolin’in antihiperaljezik etkisi her iki testte de, uygulanan hemikolinium-3 (yüksek afiniteli kolin geri alım blokörü,1 µg), mekamilamin (seçici olmayan nikotinik reseptör antagonisti,50 µg), alfa-bungarotoksin (α7 nöronal nikotinik reseptör antagonisti, 2 µg) ve CGP-35348 (GABAB reseptör antagonisti, 20 µg) ön tedavileri ile baskılandı. Atropin (seçici olmayan muskarinik reseptör antagonisti, 10 µg) ve nalokson (seçici olmayan opioid reseptör antagonisti,10 µg) ön tedavileri ise CDP-kolin’in antihiperaljezik etkisini değiştirmedi. CDP-kolin’in (2µmol, intraserebroventriküler) carrageenana bağlı gelişen pençe ödemini azaltmadığı gözlemlendi. Elde edilen bulgular, sıçanlarda inflamatuvar ağrı modelinde CDP-kolin’in antihiperaljezik etki yaptığını ortaya koymuştur. Presinaptik kolinerjik mekanizmaların aktivasyonu aracılığıyla santral α7 nikotinik kolinerjik reseptörlerin uyarılması CDPkolin’in antihiperaljezik etkisindeki muhtemel mekanizma olarak görünmektedir. Santral GABAB reseptörler, CDP-kolin’in antihiperaljezik etkisinde rol oynarken; opioid reseptörlerin rolü görülmemiştir.
CDP-choline, a nucleotid compound endogenously produced by the organism, elicits analgesic effects in acute pain models in rats. In this study, the effects of CDP-choline on both hyperalgesia and the carrageenan-induced paw edema were investigated and the analgesic effect was evaluated in an experimental inflammatory pain model. Experiments were performed on male Sprague-Dawley rats. All drugs were prepared in saline and administered intracerebroventricularly in 10 µl volume. Inflammation was produced by injection of 2% lambda-carrageenan (100 µl) to right hind paws of rats intraplantarly. Termal paw plantar test and mechanical paw pressure test were used to measure the antihyperalgesic effect. The width of hind paws was measured with digital microcaliper to expose the effect of CDP-choline on the carrageenan-induced paw edema. CDP-choline (0.5, 1, 2 µmol) exerted antihyperalgesic effect in a dose and time dependent manner in both tests. Equimolar doses of CDP-choline (1 µmol) and choline showed similar antihyperalgesic effects, while cytidine (1 µmol) did not change the thermal paw withdrawal latency but showed antihyperalgesic effect at the fifth minute of the mechanical paw pressure test. Hemicholinium-3 (high affinity choline uptake blocker, 1 µg), mecamylamine (nonspecific nicotinic receptor antagonist, 50 µg), alphabungarotoxin (selective α7 nicotinic receptor antagonist, 2 µg) and CGP-35348 (GABAB receptor antagonist, 20 µg) pretreatments abolished the antihyperalgesic effect of CDPcholine in both experimental pain models in rats. Atropine (nonspecific muscarinic receptor antagonist,10 µg) and naloxone (non-specific opioid receptor antagonist, 10 µg) pretreatments failed to alter the antihyperalgesic effect of CDP-choline. CDP-choline (2µmol, intracerebroventricularly) did not decrease the edema induced by carrageenan. These results indicate that CDP-choline induced dose and time dependent antihyperalgesic effect in inflammatory model of pain in rats. Activation of specific α7 nicotinic cholinergic receptors through the activation of presynaptic cholinergic mechanisms appear to be involved in the antihyperalgesic effect of this drug. Central GABAB receptors, but not opioid receptors, seem to be involved in this effect of CDPcholine.
CDP-choline, a nucleotid compound endogenously produced by the organism, elicits analgesic effects in acute pain models in rats. In this study, the effects of CDP-choline on both hyperalgesia and the carrageenan-induced paw edema were investigated and the analgesic effect was evaluated in an experimental inflammatory pain model. Experiments were performed on male Sprague-Dawley rats. All drugs were prepared in saline and administered intracerebroventricularly in 10 µl volume. Inflammation was produced by injection of 2% lambda-carrageenan (100 µl) to right hind paws of rats intraplantarly. Termal paw plantar test and mechanical paw pressure test were used to measure the antihyperalgesic effect. The width of hind paws was measured with digital microcaliper to expose the effect of CDP-choline on the carrageenan-induced paw edema. CDP-choline (0.5, 1, 2 µmol) exerted antihyperalgesic effect in a dose and time dependent manner in both tests. Equimolar doses of CDP-choline (1 µmol) and choline showed similar antihyperalgesic effects, while cytidine (1 µmol) did not change the thermal paw withdrawal latency but showed antihyperalgesic effect at the fifth minute of the mechanical paw pressure test. Hemicholinium-3 (high affinity choline uptake blocker, 1 µg), mecamylamine (nonspecific nicotinic receptor antagonist, 50 µg), alphabungarotoxin (selective α7 nicotinic receptor antagonist, 2 µg) and CGP-35348 (GABAB receptor antagonist, 20 µg) pretreatments abolished the antihyperalgesic effect of CDPcholine in both experimental pain models in rats. Atropine (nonspecific muscarinic receptor antagonist,10 µg) and naloxone (non-specific opioid receptor antagonist, 10 µg) pretreatments failed to alter the antihyperalgesic effect of CDP-choline. CDP-choline (2µmol, intracerebroventricularly) did not decrease the edema induced by carrageenan. These results indicate that CDP-choline induced dose and time dependent antihyperalgesic effect in inflammatory model of pain in rats. Activation of specific α7 nicotinic cholinergic receptors through the activation of presynaptic cholinergic mechanisms appear to be involved in the antihyperalgesic effect of this drug. Central GABAB receptors, but not opioid receptors, seem to be involved in this effect of CDPcholine.
Description
Keywords
CDP-kolin, İnflamatuvar ağrı, Analjezik, Antihiperaljezik, Nikotinik reseptörler, CDP-choline, Inflammatory pain, Analgesic, Antihyperalgesic, Nicotinic receptors
Citation
Bağdaş, D. (2008). Deneysel inflamatuvar ağrı modelinde CDP-kolinin analjezik etkisi ve etki mekanizması. Yayınlanmamış doktora tezi. Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.