title: The effects of subarachnoid administration of preservative-free S(+)-ketamine on spinal cord and meninges in dogs.
abstract: BACKGROUND
  The N-methyl-d-aspartate receptor antagonist ketamine and its active enantiomer, S(+)-ketamine, have been injected in the epidural and subarachnoid spaces to treat acute postoperative pain and relieve neuropathic pain syndrome. In this study we evaluated the effects of a single dose of preservative-free S(+)-ketamine, in doses usually used in clinical practice, in the spinal cord and meninges of dogs.
  
  
  METHODS
  Under anesthesia (IV etomidate (2 mg/kg) and fentanyl (0.005 mg/kg), 16 dogs (6 to 15 kg) were randomized to receive a lumbar intrathecal injection (L5/6) of saline solution of 0.9% (control group) or S(+)-ketamine 1 mg/kg(-1) (ketamine group). All doses were administered in a volume of 1 mL over a 10-second interval. Accordingly, injection solution ranged from 0.6% to 1.5%. After 21 days of clinical observation, the animals were killed; spinal cord, cauda equina root, and meninges were removed for histological examination with light microscopy. Tissues were examined for demyelination (Masson trichrome), neuronal death (hematoxylin and eosin) and astrocyte activation (glial fibrillary acidic protein).
  
  
  RESULTS
  No clinical or histological alterations of spinal tissue or meninges were found in animals from either control or ketamine groups.
  
  
  CONCLUSIONS
  A single intrathecal injection of preservative-free S(+)-ketamine, at 1 mg/kg(-1) dosage, over a concentration range of 6 to 15 mg/mL injected in the subarachnoid space in a single puncture, did not produce histological alterations in this experimental model.
authors.affiliation: Anesthesiology Department, Sao Paulo State University, Botucatu/SP, Brazil.
authors.forename: Alfredo Cury
authors.initials: AC
authors.lastname: Rojas
authors.forename: Juliana Gaiotto
authors.initials: JG
authors.lastname: Alves
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Moreira E Lima
authors.forename: Mariângela
authors.initials: M
authors.lastname: Esther Alencar Marques
authors.forename: Guilherme Antônio
authors.initials: GA
authors.lastname: Moreira de Barros
authors.forename: Fernanda Bono
authors.initials: FB
authors.lastname: Fukushima
authors.forename: Norma Sueli Pinheiro
authors.initials: NS
authors.lastname: Modolo
authors.forename: Eliana Marisa
authors.initials: EM
authors.lastname: Ganem
mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007278:Injections, Spinal; D007649:Ketamine / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008578:Meninges / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism; D011310:Preservatives, Pharmaceutical / Q000737:chemistry*; D011897:Random Allocation; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D000700:Analgesics; D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D011310:Preservatives, Pharmaceutical; D007649:Ketamine