Amin B, Avaznia M, Noorani R, Mehri S, Hosseinzadeh H. Upregulation of Glutamate Transporter 1 by Clavulanic Acid Administration and Attenuation of Allodynia and Hyperalgesia in Neuropathic Rats. BCN 2019; 10 (4) :345-354
URL:
http://bcn.iums.ac.ir/article-1-747-en.html
1- Cellular and Molecular Research Center, Department of Physiology and Pharmacology, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran.
2- Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
3- Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. ; Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract:
Introduction: Clavulanic acid (CLAV) is structurally similar to ceftriaxone, a potent stimulator of glial GlutamateTransporter-1 (GLT-1) expression. The present study aims at exploring the anti-nociceptive effects of CLAV, a beta-lactamase inhibitor in rats underwent sciatic nerve Chronic Constriction Injury (CCI).
Methods: CLAV (12.5, 25, 50 mg/kg) was administered intraperitoneally after the surgery for 14 consecutive days. Behavioral pain parameters were evaluated before and 3, 5, 7, 10 and 14 days after injury. Spinal GLT-1 level was measured via western blotting at days 7 and 14.
Results: CCI led to mechanical allodynia, cold allodynia and thermal hyperalgesia which started on postoperative days 3 and continued until the end of study. We found that CLAV (12.5 and 25 mg/kg) significantly attenuated all pain related behaviors as compared to the CCI animals treated with normal saline. Protein level of GLT-1 was down-regulated on day 14 following CCI and this phenomenon was reversed by fourteen days treatment of CLAV at the low doses of 12.5 and 25 mg/kg.
Conclusion: These results suggest that CLAV might provide a new therapeutic strategy for neuropathic pain and its effect might be partially associated with the up-regulation of GLT-1.
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Highlights
• Clavulanic acid showed anti-allodynic and anti-hyperalgesic effects in animal models with neuropathic pain.
• GLT1 protein decreased in the spinal cord of neuropathic animals.
• The antinociceptive effects of clavulanic acid in neuropathic rats depend on GLT-1 up-regulation.
Plain Language Summary
Neuropathic pain is a challenge in clinical practice. The recommended drugs for the pain have many side effects with limited efficacy. Clavulanic Acid (CLAV) is a member of β-lactam antibiotics, such as penicillins and cephalosporins. It has been reported that CLAV has neuroprotective effects in some studies. In this work, chronic constriction injury (CCI) of sciatic nerve induced increased sensitivity to mechanical and cold stimuli. Administration of CLAV immediately after the injury could attenuate pain developed in CCI animals. Based on our results, glutamate transporter (GLT1) content decreased in CCI animals treated with normal saline. This protein is responsible for preventing the toxicity of glutamate to brain cells. The level of GLT1 was high after intraperitoneal administration of CLAV in the lumbar spinal cord of CCI rats.
Type of Study:
Original |
Subject:
Behavioral Neuroscience Received: 2016/03/27 | Accepted: 2017/09/26 | Published: 2019/07/1