The beta-lactam antibiotic, ceftriaxone, inhibits the development of opioid-induced hyperalgesia in mice.
The glutamate transporter GLT-1 is primarily responsible for glutamate clearance in the spinal cord. beta-Lactam antibiotics have been shown to attenuate neuropathic pain behaviors by promoting GLT-1 expression and function in the CNS. The present study tested the hypothesis that ceftriaxone, a prototype beta-lactam antibiotic, can prevent the development of opioid-induced hyperalgesia (OIH) in mice. Repeated morphine administration produced mechanical allodynia and thermal hyperalgesia, signs of OIH, and reduced spinal GLT-1 expression in mice. Ceftriaxone (200mg/kg/d, i.p., for 7 d) inhibited OIH. Correlating with the behavioral effects, ceftriaxone reversed downregulation of GLT-1 expression that was induced by OIH. These results suggest that ceftriaxone inhibited the development of OIH by up-regulating spinal GLT-1 expression.
Department of Biopharmaceutical Sciences and Cancer Center, University of Illinois, Chicago, IL 60612, USA.
Zhijun
Z
Chen
Ying
Y
He
Zaijie Jim
ZJ
Wang
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002443:Ceftriaxone / Q000008:administration & dosage / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology; D015854:Up-Regulation / Q000187:drug effects; D047090:beta-Lactams / Q000494:pharmacology*
D000701:Analgesics, Opioid; D000900:Anti-Bacterial Agents; D027342:Excitatory Amino Acid Transporter 2; D047090:beta-Lactams; D002443:Ceftriaxone; D009020:Morphine