Nursima ÇUKADAR, Furkan BARAN, Kadir ÖZSOY, Fatih UYANIK, Tuba SÜRER, Tufan MERT, Yasemin GÜNEŞ

Lokal Metoprolol Uygulamasının Nosiseptif Etkileri

Amaç: Beta (β)-adrenerjik reseptör antagonisti olan metoprolol, antihipertansif ve antitaşikardik etkileri nedeniyle kardiyovasküler sistem hastalığı olan kişilerde anestezi sırasında dolaşım sistemi komplikasyonları önlemek için kullanılmaktadır. Sistemik metoprolol’un antinosiseptif ve anestezik etkileri sahip olduğunu gösteren birkaç çalışma olmasına rağmen, ağrı algısını da içeren nosiseptif süreçlerindeki etkilerine ilişkin bilgi oldukça sınırlıdır. Bu nedenle bu çalışma bir β--adrenerjik reseptör antagonisti olan metoprolol’un lokal uygulama sonrası muhtemel anti nosiseptif veya hiper nosiseptif etkilerini belirlemek için planlandı. Metoprolol bulguları β--adrenerjik reseptör agonisti dobutaminle karşılaştırıldı. Materyal ve Metod: Lokal (intraplantar) olarak uygulanan metoprololun etkileri, duysal fonksiyon testleri olan termal plantar test ve mekanik plantar test teknikleri kullanılarak araştırıldı. Bulgular: Antagonist metoprolol termal latansı ve mekanik eşiği doza ve zamana bağlı olarak anlamlı bir şeklide azalttı. Bununla beraber, agonist dobutamin, metoprololun aksine latans ve eşik parametrelerini doz ve zaman bağlı olarak arttırdı. Araştırma Makalesi / Research Article 258 Cilt/Volume 40 Yıl/Year 2015 Metoprolol- Nosiseptif Etkileri Sonuç: Bulgular lokal olarak uygulanan metoprolol’un hiperaljezi ve allodini oluşturabileceğini göstermektedir. Metoprolol ve dobutamin kullanılarak elde edilen veriler, periferik β-adrenerjik reseptörlerin nosiseptif süreçte önemli roller oynayabileceğini işaret etmektedir

Anahtar Kelimeler:

Metoprolol, İntraplantar, Hiperaljezi, Allodini, Sıçan

Nociceptive Effects of Locally Treated Metoprolol

Purpose: Beta (β-)-adrenergic receptor antagonists, such as metoprolol, are often used to avoid circulatory complications during anesthesia for their antihypertensive and anti-tachycardia effects in patients with cardiovascular diseases. Although a few previous studies have been reported to exert antinociceptive and anesthetic effects of these drugs, knowledge about their action mechanisms in nociceptive process including pain perception is limited. This study therefore designed to identify the roles underlying the probable anti or hyper nociceptive effects of metoprolol, a β- adrenergic receptor antagonist. In addition, effects of metoprolol were compared the dobutamin, a β-adrenergic agonist. Material and Methods: To investigate the effects of β-adrenergic receptor blocker, metoprolol, sensor functions using thermal plantar test (hyperalgesia) and dynamic plantar aesthesiometer (allodynia) techniques were examined in the rats after local (intraplantar) injection to paws. Results: Metoprolol, an antagonist, significantly decreased the thermal latency and mechanical thresholds with dose and time dependent manner. However, dobutamine, an agonist, enhanced the latency and thresholds dose and time dependent. Conclusions: This results suggest that ın contrast to dobutamine, locally treated metoprolol may cause hyperalgesic and allodynic actions. In addition, our results can demonstrate that peripheral β-adrenergic receptors can play important roles in nociceptive process

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Bars DL, Gozariu M, Cadden SW. Animal models of nociception. Pharmacol Rev. 2001;53:597–652.
Andrew D, Greenspan JD. Mechanical and heat sensitization of cutaneous nociceptors after 13. Zhang HT, Huang Y, O’Donnell JM. Antagonism of peripheral inflammation in the rat J. Neurophysiol. 1999;82:2649–56.
Fechoa K, Nackley AG, Wu Y, Maixner W. Basal and carrageenan-induced pain behavior in Sprague– Dawley,Lewis and Fischer rats. Physiol Behav. 2005;85:177-86.
Mert T, Ocal I, Gunay I, Pain relieving effects of pulsed magnetic fields in a rat model of carrageenan- induced hindpaw inflammation Int Rad Biol. 2014;90:95–103.
Volz-Zang C, Eckrich B, Jahn P, et al. Esmolol, an ultrashort-acting, selective beta 1-adrenoceptor antagonist: pharmacodynamic and pharmacokinetic properties. Eur J Clin Pharmacol. 1994;46:399–404.
Davidson EM, Doursout MF, Szmuk P, Chelly JE. Antinociceptive and cardiovascular properties of esmolol following formalin injection in rats. Can J Anaesth. 2001;48:59–64.
Tanahashi S, Lida H, Dohi S, Oda A, Osawa Y, Yamaguchi S. Comparative effects of ultra-short- acting b1-blockers on voltage-gated tetrodotoxin- resistant Na channels in rat sensory neurons. Eur J Anaesth. 2009;26:196–200.
Johansen JW, Flaishon R, Sebel PS. Esmolol reduces anesthetic requirement for skin incision during propofol/nitrous oxide/morphine anesthesia. Anesthesiology. 1997;87:461–2.
Khasar SG, Mccarter G, Levıne JD. Epinephrine
Produces a b-Adrenergic Receptor-Mediated Mechanical Hyperalgesia and In Vitro Sensitization of Rat Nociceptors. J Neurophysiol. 1999;81:1104-12
Hein L, Kobilka BK. Adrenergic receptor signal transduction and regulation. Neuropharmacol. 1995;34:357–66.
Hein L. Adrenoreceptors and signal transduction in neurons. Cell Tissue Res. 2006;326:541–51.
Yu BH, Dimsdale JE, Mills PJ. Psychological states and lymphocyte beta-adrenergic receptor responsiveness. Neuropsychopharmacol. 1999;21:147–52. the antidepressant-like effects of clenbuterol by central administration of beta-adrenergic antagonists in rats. Psychopharmacol. 2003;170:102–7.
Tuttle RR, Mills J. Dobutamine: development of a new catecholamine to selectively increase cardiac contractility. Circ Res. 1975;36:185–96.
Najafipour H. Alteration in alpha- and beta- adrenoceptor profile of rabbit knee joint blood vessels due to acute inflammation. Exp Physiol. 2000;85:267–73.
Koltzenburg M. Neural mechanisms of cutaneous nociceptive pain. Clin J Pain. 2000;16:131–8.
Sawynok, J. Topical and peripherally acting analgesics. Pharmacological Reviews. 2003;55:1–20.