CDP-kolin'in analjezik etkisi ve etkiye aracılık eden mekanizmalar
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Date
2007
Authors
Hamurtekin, Emre
Journal Title
Journal ISSN
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Publisher
Uludağ Üniversitesi
Abstract
Bu çalışmada, sıçanlarda akut ağrı modellerinde intraserebroventriküler (i.s.v.) yolla uygulanan CDP-kolin’in analjezik etkisi araştırıldı. Deneylerde 300-350 g ağırlığında Sprague-Dawley erkek sıçanlar kullanıldı. İlaçlar, sıçanların sağ serebral yan ventriküllerine yerleştirilen kılavuz kanül aracılığı ile i.s.v. yolla uygulandı. Sıçanların akut ağrı duyarlılığı termal ve mekanik pençe çekme testi kullanılarak değerlendirildi. İ.s.v. yolla uygulanan CDP-kolin’in motor performans üzerine olan etkilerini değerlendirmek için rota-rod testi kullanıldı. CDP-kolin (0.5, 1 ve 2 µmol; i.s.v.) termal ve mekanik akut ağrı modellerinde doza ve zamana bağlı olacak şekilde analjezik etki meydana getirdi. Eşmolar dozlardaki kolin (1 µmol; i.s.v.) ve CDP-kolin (1 µmol; i.s.v.) birbirine benzer şekilde bir analjezik etki meydana getirirken, sitidin (1 µmol; i.s.v.) analjezik etki meydana getirmedi. CDP-kolin’in analjezik etkisi her iki testte de, i.s.v. yolla uygulanan yüksek afiniteli kolin geri alım blokeri HC-3 (1 µg), seçici olmayan nikotinik reseptör antagonisti mekamilamin (50 µg), α7 nöronal nikotinik reseptör antagonisti MLA (25 µg), seçici olmayan opioid reseptör antagonisti nalokson (10 µg) ve GABAB reseptör antagonisti CGP35348 (20 µg) ön tedavileri ile bloke oldu. Seçici olmayan muskarinik reseptör antagonisti atropin (10 µg), α-1 adrenerjik reseptör antagonisti prazosin (20 µg) ve α-2 adrenerjik reseptör antagonisti yohimbin (30 µg) ile seçici olmayan serotonin reseptör antagonisti metiserjid (20 µg) ön tedavileri ise CDP-kolin’in analjezik etkisini değiştirmedi. Bulgularımız, sıçanlardaki akut ağrı modellerinde CDP-kolin’in motor inkoordinasyona neden olmadan analjezik etki yaptığını göstermektedir. Presinaptik kolinerjik mekanizmaların aktivasyonu aracılığı ile santral α7nikotinik kolinerjik reseptörlerin uyarılması CDP-kolin’in analjezik etkisindeki muhtemel mekanizma olarak görünmektedir. Aynı zamanda santral GABAB ve opioid reseptörler, CDP-kolin’in analjezik etkisinde rol oynamaktadırlar.
In the present study, the analgesic effect of intracerebroventricularly (i.c.v.) injected CDP-choline on acute pain models of rats was investigated. Experiments were performed on male Sprague-Dawley rats weighing 300-350 g. All drugs were administered i.c.v. by a guide cannula which was implanted to the right lateral ventricle of the rats. The pain sensitivity of rats was determined using thermal paw withdrawal test and mechanical paw pressure test. Rats were also tested on a rota-rod test to evaluate the effects of i.c.v. injected CDP-choline on motor performance. CDP-choline (0.5, 1 and 2 µmol; i.c.v.) produced dose and timedependent analgesia on both thermal and mechanical acute pain models. Equimolar dose of choline (1 µmol; i.c.v.) produced an analgesic effect similar to the one observed in CDP-choline (1 µmol; i.c.v.) given animals. However, cytidine (1 µmol; i.c.v.) failed to produce an analgesic effect. The analgesic effect of CDP-choline was prevented by i.c.v. administered high affinity choline uptake inhibitor HC-3 (1 µg), nonselective nicotinic receptor antagonist mecamylamine (50 µg), α7 neuronal nicotinic receptor antagonist MLA (25 µg), non-spesific opioid receptor antagonist naloxone (10 µg) and GABAB receptor antagonist CGP-35348 (20 µg) pretreatments in both tests. Nonselective muscarinic receptor antagonist atropine (10 µg), α-1 adrenergic receptor antagonist prazosin (20 µg), α-2 adrenergic receptor antagonist yohimbine (30 µg) and non-spesific serotonin receptor antagonist methysergide (20 µg) pretreatments did not change the analgesic effect of CDP-choline. Our results show that CDP-choline exerts an analgesic effect without producing any motor incoordination on acute pain models in rats. Activation of central α7-nicotinic cholinergic receptors through the activation of presynaptic cholinergic mechanisms appears to be the possible mechanism in the analgesic effect of CDP-choline. Also central GABAB and opioid receptors seem to be involved in the analgesic effect of this drug.
In the present study, the analgesic effect of intracerebroventricularly (i.c.v.) injected CDP-choline on acute pain models of rats was investigated. Experiments were performed on male Sprague-Dawley rats weighing 300-350 g. All drugs were administered i.c.v. by a guide cannula which was implanted to the right lateral ventricle of the rats. The pain sensitivity of rats was determined using thermal paw withdrawal test and mechanical paw pressure test. Rats were also tested on a rota-rod test to evaluate the effects of i.c.v. injected CDP-choline on motor performance. CDP-choline (0.5, 1 and 2 µmol; i.c.v.) produced dose and timedependent analgesia on both thermal and mechanical acute pain models. Equimolar dose of choline (1 µmol; i.c.v.) produced an analgesic effect similar to the one observed in CDP-choline (1 µmol; i.c.v.) given animals. However, cytidine (1 µmol; i.c.v.) failed to produce an analgesic effect. The analgesic effect of CDP-choline was prevented by i.c.v. administered high affinity choline uptake inhibitor HC-3 (1 µg), nonselective nicotinic receptor antagonist mecamylamine (50 µg), α7 neuronal nicotinic receptor antagonist MLA (25 µg), non-spesific opioid receptor antagonist naloxone (10 µg) and GABAB receptor antagonist CGP-35348 (20 µg) pretreatments in both tests. Nonselective muscarinic receptor antagonist atropine (10 µg), α-1 adrenergic receptor antagonist prazosin (20 µg), α-2 adrenergic receptor antagonist yohimbine (30 µg) and non-spesific serotonin receptor antagonist methysergide (20 µg) pretreatments did not change the analgesic effect of CDP-choline. Our results show that CDP-choline exerts an analgesic effect without producing any motor incoordination on acute pain models in rats. Activation of central α7-nicotinic cholinergic receptors through the activation of presynaptic cholinergic mechanisms appears to be the possible mechanism in the analgesic effect of CDP-choline. Also central GABAB and opioid receptors seem to be involved in the analgesic effect of this drug.
Description
Keywords
CDP-kolin, Akut ağrı, Analjezi, Nikotinik reseptörler, CDP-choline, Acute pain, Analgesia, Nicotinic receptors
Citation
Hamurtekin, E. (2007). CDP-kolin'in analjezik etkisi ve etkiye aracılık eden mekanizmalar. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.