Upregulation of Glutamate Transporter 1 by Clavulanic Acid Administration and Attenuation of Allodynia and Hyperalgesia in Neuropathic Rats

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.