Analgesic effect of a single preoperative dose of the antibiotic ceftriaxone in humans.

Repeated injections of the antibiotic ceftriaxone cause analgesia in rodents by upregulating the glutamate transporter, GLT-1. No evidence is available in humans. We studied the effect of a single intravenous administration of ceftriaxone in patients undergoing decompressive surgery of the median or ulnar nerves. Forty-five patients were randomized to receive saline, ceftriaxone (2 g), or cefazolin (2 g), 1 hour before surgery. Cefazolin, which is structurally related to ceftriaxone, was used as a negative control. Pain thresholds were measured 10 minutes before drug injections and then 4 to 6 hours after surgery. Ceftriaxone caused analgesia in all patients, whereas cefazolin was inactive. We also performed animal studies to examine whether a single dose of ceftriaxone was sufficient to induce analgesia. A single intraperitoneal injection of ceftriaxone (200 mg/kg), but not cefazoline (200 mg/kg), caused analgesia in mouse models of inflammatory or postsurgical pain, and upregulated GLT-1 in the spinal cord. Ceftriaxone-induced analgesia was additive to that produced by blockade of mGlu5 receptors, which are activated by extrasynaptic glutamate. These data indicate that a single dose of ceftriaxone causes analgesia in humans and mice and suggest that ceftriaxone should be used for preoperative antimicrobial prophylaxis when a fast relief of pain is desired.