title: Spinal nociception induced by intramuscular injection of oxytetracycline preparations in rats and pigs.
abstract: Some drug formulations for intramuscular use may cause damage, which potentially can be associated with pain. In animals, spinal nociception can be assessed by stereological quantification of number of regional dorsal horn neurones containing intranuclear Fos-protein as a consequence of expression of the c-fos gene. The aim of the present study was to use c-fos gene expression as a measure of nociceptive input after intramuscular injection of different oxytetracycline formulations. Rats were given a 0.3 ml intramuscular injection in the thigh of one of two 100 mg/ml oxytetracycline preparations (Maxicyklin Vet., Boehringer-Ingelheim or Engemycin Vet., Intervet; n=6 for both), 0.9% saline (n=4) or 4% formalin (n=2). In addition, five pigs were given an intramuscular injection of Aquacykline Vet. (Rosco) in a dose of 1.0 ml/10 kg. After three hours the animals were anaesthetised and perfusion fixed and their spinal cords were taken out. Cryostate sections of the spinal cords were stained immunohistochemically for Fos-protein in dorsal horn neurones and then subjected to stereological quantification of Fos-positive neurones. Rats receiving a saline injection had 905+/-586 (mean+/-S.D.) Fos-positive neurones, whereas formalin injection increased this number to 11,091+/-4,825. Rats receiving an injection of Engemycin had 1,932+/-893 Fos-positive neurones, which was not significantly different from the saline group. In contrast, injection with Maxicyklin increased the number of Fos-positive neurones to 5,488+/-3,116, which was higher than after injection of saline (P<0.05). In pigs receiving an Aquacyklin injection, the number of Fos-positive neurones was 3,493+/-2,027, which was not significantly higher than the previously determined basal level. The increased neuronal activation after intramuscular injection of Maxicyklin Vet. may suggest that injection of this drug may be more painful than injection with saline. In contrast, no significant difference in neuronal activation caused by saline and Engemycin Vet. was found.
authors.affiliation: Department of Veterinary Pathobiology, The Royal Veterinary and Agricultural University, DK-1870 Frederiksberg C, Copenhagen, Denmark. os@kvl.dk
authors.forename: Ove
authors.initials: O
authors.lastname: Svendsen
authors.forename: Camilla B
authors.initials: CB
authors.lastname: Andersen
authors.forename: Carina B
authors.initials: CB
authors.lastname: Mørkhøj
authors.forename: Brian
authors.initials: B
authors.lastname: Lauritzen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D007273:Injections, Intramuscular; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects*; D010118:Oxytetracycline / Q000008:administration & dosage / Q000494:pharmacology*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013552:Swine
chemical_list: D000900:Anti-Bacterial Agents; D016760:Proto-Oncogene Proteins c-fos; D010118:Oxytetracycline