Browsing by Author "Baǧdaş, Deniz"
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Item Antihyperalgesic activity of chlorogenic acid in experimental neuropathic pain(Springer, 2013-10) Baǧdaş, Deniz; Çinkılıç, Nilüfer; Özbölük, Hasret Yücel; Özyiǧit, Musa Özgür; Gürün, Mine Sibel; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; Uludağ Üniversitesi/Veteriner Fakültesi/Patoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Hayvan Yetiştiriciliği, Beslenme ve Et Araştırma Enstitüsü.; 0000-0002-3595-6286; AAR-6478-2021; AAG-8716-2019; AAH-5296-2021; AAH-2873-2021; 15062425700; 26533892300; 55890590200; 6507338060; 55664349700Chlorogenic acid (CGA) is a natural organic phenolic compound that is found in many plants, fruits and vegetables. CGA has beneficial bioactivities and strong therapeutic effects in inflammatory processes. CGA-rich fractions have analgesic activity but CGA has not been tested previously in neuropathic pain, which results from tissue damage, inflammation or injury of the nervous system. Chronic constrictive nerve injury (CCI) is a peripheral neuropathic pain model which initiates an inflammatory cascade. We aimed to determine possible antihyperalgesic effects of CGA in neuropathic pain. Our study showed for the first time that CGA [50, 100 and 200 mg/kg; intraperitoneally (i.p.)] produced significant dose- and time-dependent antihyperalgesic activity in CCI-induced neuropathic pain. In addition, chronic administration of CGA (100 mg/kg/day; i.p. for 14 days) prevented the development of mechanical hyperalgesia and attenuated CCI-induced histopathological changes. On the other hand, CGA (200 mg/kg) did not affect falling latencies of rats in the rota rod test. Hence, CGA might represent a novel potential therapeutic option for the management of neuropathic pain.Item Diacylglycerol lipase beta inhibition reverses nociceptive behaviour in mouse models of inflammatory and neuropathic pain(Wiley, 2016-02-16) Wilkerson, Jenny L.; Ghosh, Sudeshna; Mason, Brittany L.; Crowe, Molly S.; Hsu, Kulung; Wise, Laura E.; Kinsey, Steven G.; Damaj, Mohamad Imad; Cravatt, Benjamin F.; Lichtman, Aron H.; Baǧdaş, Deniz; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi.; 15062425700Background and PurposeInhibition of diacylglycerol lipase (DGL) prevents LPS-induced pro-inflammatory responses in mouse peritoneal macrophages. Thus, the present study tested whether DGL inhibition reverses allodynic responses of mice in the LPS model of inflammatory pain, as well as in neuropathic pain models. Experimental ApproachInitial experiments examined the cellular expression of DGL and inflammatory mediators within the LPS-injected paw pad. DAGL- (-/-) mice or wild-type mice treated with the DGL inhibitor KT109 were assessed in the LPS model of inflammatory pain. Additional studies examined the locus of action for KT109-induced antinociception, its efficacy in chronic constrictive injury (CCI) of sciatic nerve and chemotherapy-induced neuropathic pain (CINP) models. Key ResultsIntraplantar LPS evoked mechanical allodynia that was associated with increased expression of DGL, which was co-localized with increased TNF- and prostaglandins in paws. DAGL- (-/-) mice or KT109-treated wild-type mice displayed reductions in LPS-induced allodynia. Repeated KT109 administration prevented the expression of LPS-induced allodynia, without evidence of tolerance. Intraplantar injection of KT109 into the LPS-treated paw, but not the contralateral paw, reversed the allodynic responses. However, i.c.v. or i.t. administration of KT109 did not alter LPS-induced allodynia. Finally, KT109 also reversed allodynia in the CCI and CINP models and lacked discernible side effects (e.g. gross motor deficits, anxiogenic behaviour or gastric ulcers). Conclusions and ImplicationsThese findings suggest that local inhibition of DGL at the site of inflammation represents a novel avenue to treat pathological pain, with no apparent untoward side effects.Item Nicotinic receptors as targets for novel analgesics and anti-infl ammatory drugs(Humana Press Inc, 2014) Damaj, Mohamad Imad; Freitas, Kelen C.C.; Flood, Pamela Dru; Lester, R. A. J.; Baǧdaş, Deniz; Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi.; 15062425700Nicotine and nicotinic receptors have been explored for the past three decades as a strategy for pain control. These receptors are widely expressed throughout the central and peripheral nervous system as well as immune cells. Despite encouraging results with many selective alpha 4 beta 2* agonists in animal models of pain, human studies showed a narrow therapeutic window between analgesic efficacy and toxicity is associated with the use of these agonists as analgesics. alpha 4 beta 2 positive allosteric modulators are being developed with the aim to increase the potency or therapeutic window of these agonists. However, several recent developments have potentially opened new windows of opportunity in the use of nicotinic agents for analgesia. Accumulating evidences suggest that alpha 7 agonists and positive allosteric modulators hold a lot of promise in the treatment of chronic inflammatory pain conditions. In addition, recent animal studies suggest the therapeutic potential of ligands acting at other subtypes of nicotinic receptors. The current review will attempt to highlight these recent developments and outline some important findings that demonstrate further potential for the development of nicotinic ligands as novel analgesics.Item The protective effect of ClinOleic against post-surgical adhesions(Turkish Assoc Trauma Emergency Surgery, 2014-01) Altınel, Yüksel; Taşpınar, Ersoy; Özgüç, Halil; Öztürk, Ersin; Ülker , Elif Akyıldız; Baǧdaş, Deniz; Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; Uludağ Üniversitesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi.; AAL-9231-2020; 26657125600; 55993367600; 6603867989; 35070171400; 8559530600; 15062425700BACKGROUND: Although the English-language literature is full of studies about post-surgical adhesions, no definitive method has yet been identified to prevent them. The goal of this study was to investigate the effect of ClinOleic on reducing post-surgical adhesion formation. METHODS: Surgery was performed on 40 adult female Sprague-Dawley rats that were randomly assigned to receive either intraperitoneal ClinOleic, which was used to mimic chyle (ClinOleic group), soybean oil (soybean oil group), olive oil (olive oil group), or 0.9% NaCl suspension (control group). All rats underwent laparotomy, side-wall and cecal abrasion, and primary closure. On the 30th day following surgery, rats were sacrificed and examined using the Majuzi adhesion classification and histopathological grading scales. RESULTS: The adhesion and histopathological scores of the ClinOleic group were significantly lower compared to the control group (0.9% NaCl) (p<0.05). A statistically significant decrease in fibrosis was observed in the soybean and olive oil groups when compared to the control group (p<0.05). However, the adhesion grades of the ClinOleic, soybean and olive oil groups were comparable. We did not observe any post-surgical adhesions in the ClinOleic group. CONCLUSION: The parenteral nutrition solution ClinOleic may be an effective and readily available agent for the prevention of post-surgical adhesions.Item Role of central arginine vasopressin receptors in the analgesic effect of CDP-choline on acute and neuropathic pain(Lippincott Williams and Wilkins, 2013-12-04) Baǧdaş, Deniz; Özbölük, Hasret Yücel; Orhan, Fulya; Kanat, Özkan; Büyükcoşkun, Naciye Işbil; Gürün, Mine Sibel; Uludağ Üniversitesi/Tıp Fakültesi/Farmokoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; AAH-1692-2021; AAG-8716-2019; 15062425700; 55865772300; 55866311800; 55881548500; 55665951400; 55664349700Recent studies have demonstrated that arginine vasopressin (AVP) plays a crucial role in pain modulation. In addition, our previous studies have proven that centrally administered cytidine-5-diphosphate-choline (CDP-choline; citicoline) elicits an analgesic effect in different pain models in rats. Given that CDP-choline enhances central and peripheral vasopressin levels, the present study was designed to investigate the role of central AVP receptors in the analgesic effect of CDP-choline in acute and chronic constriction injury-induced neuropathic pain models. For this purpose, rats were pretreated intracerebroventricularly with the AVP V-1 or AVP V-2 receptor antagonist 15 min before intracerebroventricular injection of CDP-choline or saline, and pain threshold was determined using the Randall-Selitto test. AVP V-1 and AVP V-2 receptor antagonist blocked the CDP-choline-induced analgesic effect either in acute or neuropathic models of pain in rats. These results suggest, for the first time, that central AVP receptors are involved in the CDP-choline-elicited analgesic effect.