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 antinociceptive 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 downregulated 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 upregulation of glt-1.