Evaluating the Effects of Allopurinol on the Symptoms of Chronic Constriction Injury (CCI)-Induced Neuropathic Pain with Assessing Molecular Changes in the Spinal Cord in Rat

Safari Soltanabad, Ahmad (2017) Evaluating the Effects of Allopurinol on the Symptoms of Chronic Constriction Injury (CCI)-Induced Neuropathic Pain with Assessing Molecular Changes in the Spinal Cord in Rat. Masters thesis, Sabzevar University of Medical Sciences.

Text 1.pdf Restricted to Registered users only until 20 March 3000. Download (2MB)

Abstract

Background and Aim: This study was designed to evaluate the effects of allopurinol on the neuropathic pain symptoms of chronic constriction injury of sciatic nerve (CCI), and to investigate molecular changes in the spinal cord in rats. Methods: this original study was performed on the 66 male adult Wistar rats in a randomized matter. Drug was administered simultaneously with neurological damage (preventive effect) at the doses of 30, 60 , 90 mg/kg i.p. or after induction of neuropathic pain on the day 5 (treatment effect) with the dose of 90 mg/kg. CCI-induced allodynia and hyperalgesia were measured on 1 day befor surgery and 3, 7, 10 and 14 after that. In order to identify the involved mechanisms, changes in the gene expression of apoptotic factors, bcl2, bax, caspase3, microgial activation factor, ionized calcium bindinding adapator 1 (Iba1), astroglia activation factor, glial fibrillary acidic protein (GFAP), oxidative stress factors including induced nitrioc oxid synthase (iNOS) and tumor necrosis alpha (TNF-α) were measured by real time PCR in the spinal cord of animals on day 14. A single dose of specific A1 antagonist, 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) (5 mg/kg, i.p) and a non-specific antagonist, theophylline (20 mg/kg, i.p.) were used on day 7 to evaluate the role of adenosine receptors in the development of allopurinol effects. Results: Sciatic nerve injury by CCI method reduced the sensitivity threshold of animals to Von Frey stimulants and acetone drops, which respectively indicated mechanical allodynia and cold allodynia. Thermal hyperalgesia in CCI animals was progressively increased compared to the sham group. Treatment with 90 mg/kg allopurinol in animals under CCI reduced the sensitivity of acetone drop, Von Frey and also decreased hyperalgesia in hot plate. Changes induced in the spinal cord of CCI animals were normalized by alloporinol treatment. DPCPX and theophylline reversed thermal anti-hyperalgesic effect of allopurinol. In contrast, mechanical anti-allodynic effect was only prevented by theophylline Conclusion Allopurinol through interacting with different aspects of neuropathic pain, via anti-oxidant, protection against neuroinflammation, and activating adenosine receptors could be a good candidate in treatment of patients with neuropathic pain. Key words: Allopurinol, Oxidative Stress, CCI Model, Neuropathic Pain

Item Type:	Thesis (Masters)
Uncontrolled Keywords:	Allopurinol, Oxidative Stress, CCI Model, Neuropathic Pain
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Divisions:	Faculty of Medicine, Health and Life Sciences > School of Medicine
Depositing User:	Saeed Shoja
Date Deposited:	14 May 2018 09:53
Last Modified:	14 Jan 2019 06:14
URI:	http://eprints.medsab.ac.ir/id/eprint/396

Actions (login required)

View Item