title: Anti-allodynic and anti-hyperalgesic effects of ceftriaxone in streptozocin-induced diabetic rats.
abstract: Glutamate is the principal excitatory neurotransmitter in the central nervous system. Recent evidence suggests that beta lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Moreover, these antibiotics have been shown to prevent the development of tolerance and dependence to opioids, and reduce visceral and nerve injury-induced neuropathic nociceptive responses. The aim of this study is to observe the effect of a beta lactam antibiotic, ceftriaxone, on mechanical allodynia and mechanical hyperalgesia in diabetic rats. Diabetes was produced with the injection of a single dose of streptozocin (50 mg/kg, i.p.) and this procedure resulted in neuropathic pain behaviors in the hindpaws. Mechanical allodynia was detected with an electronic aesthesiometer, and mechanical hyperalgesia was studied using the method of Randall-Selitto. With its higher doses, ceftriaxone (100, 200 mg/kg, i.p.) reduced both mechanical allodynia and hyperalgesia. Dihydrokainic acid (10 mg/kg, i.p.), a selective GLT-1 transporter inhibitor, reversed the anti-allodynic and anti-hyperalgesic effects of ceftriaxone, at doses that produced no effect on its own. Our results indicate that ceftriaxone exerts an antinociceptive effect in streptozocin-induced diabetic rats and GLT-1 activation by beta lactam antibiotics may be a promising option in the treatment of diabetic neuropathy.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Trakya University, 22030 Edirne, Turkey.
authors.forename: Ozgur
authors.initials: O
authors.lastname: Gunduz
authors.forename: Cagatay
authors.initials: C
authors.lastname: Oltulu
authors.forename: Dilek
authors.initials: D
authors.lastname: Buldum
authors.forename: Rabia
authors.initials: R
authors.lastname: Guven
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ulugol
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D002443:Ceftriaxone / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D010525:Peripheral Nerves / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D000900:Anti-Bacterial Agents; D002443:Ceftriaxone