title: Analgesic effect of a single preoperative dose of the antibiotic ceftriaxone in humans.
abstract: 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.
  
  
  CONCLUSIONS
  The study reports for the first time that a single preoperative dose of ceftriaxone causes analgesia in humans. A single dose of ceftriaxone could also relieve inflammatory and postsurgical pain and upregulate GLT-1 expression in mice. Ceftriaxone should be preferred to other antibiotics for antimicrobial prophylaxis to reduce postoperative pain.
authors.affiliation: Department of Medical and Surgical Sciences and Translational Medicine, University Sapienza, Roma, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Macaluso
authors.forename: Matteo
authors.initials: M
authors.lastname: Bernabucci
authors.forename: Angela
authors.initials: A
authors.lastname: Trabucco
authors.forename: Ludovico
authors.initials: L
authors.lastname: Ciolli
authors.forename: Fabiana
authors.initials: F
authors.lastname: Troisi
authors.forename: Rossella
authors.initials: R
authors.lastname: Baldini
authors.forename: Roberto
authors.initials: R
authors.lastname: Gradini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Battaglia
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Saul
authors.initials: S
authors.lastname: Collini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002437:Cefazolin / Q000627:therapeutic use; D002443:Ceftriaxone / Q000627:therapeutic use*; D019299:Decompression, Surgical / Q000009:adverse effects; D004195:Disease Models, Animal; D004311:Double-Blind Method; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D010523:Peripheral Nervous System Diseases / Q000601:surgery; D045442:Rotarod Performance Test; D013997:Time Factors
chemical_list: D000700:Analgesics; D027342:Excitatory Amino Acid Transporter 2; C493396:Slc1a2 protein, mouse; D002443:Ceftriaxone; D002437:Cefazolin