title: Neurotoxicity of intrathecally administered fentanyl in a rat spinal model.
abstract: OBJECTIVE
  Intrathecally administered fentanyl rarely causes drug tolerance or formation of inflammatory masses and might therefore be a suitable treatment option for chronic pain. However, the neurotoxicity of intrathecally administered fentanyl remains to be clarified. We examined the histological changes, neurodysfunction, and side effects of intrathecal fentanyl in rats.
  
  
  METHODS
  The rats received fentanyl at 0.12 µL/g body weight (0, 50, 1000, 2000, and 5000 µg/mL in saline) via an intrathecal catheter. Seven days after the injection, the spinal cord with both roots were removed for histological examination. The neurological function was evaluated by monitoring walking behavior and latencies to radiant heat. Side effects were also recorded.
  
  
  RESULTS
  No histological abnormalities were observed in the spinal cord, anterior and posterior roots, cauda equina nerves, or arachnoid membrane. Formation of white neomembrane was noted around the catheter in some animals, but there was no significant difference in the incidence among the groups. The sensory threshold was significantly higher at 1 and 2 hours after injection in the 50 and 5000 µg/mL groups, respectively. However, there was no significant difference in the sensory threshold among the five groups at 7 days postinjection. All of the rats walked normally within 4 hours even after injection of 5000 µg/mL fentanyl. The incidence of apnea, muscular rigidity, and bradycardia increased significantly at ≥ 1000 µg/mL dose.
  
  
  CONCLUSIONS
  The side effects of intrathecally administered fentanyl were concentration-dependent, although no neuronal tissue damage, inflammation, or irreversible neurodysfunction were observed even at 5000 µg/mL.
authors.affiliation: Department of Anesthesiology, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Sayano
authors.initials: S
authors.lastname: Fukushima
authors.forename: Tamie
authors.initials: T
authors.lastname: Takenami
authors.forename: Saburo
authors.initials: S
authors.lastname: Yagishita
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nara
authors.forename: Sumio
authors.initials: S
authors.lastname: Hoka
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D057785:Catheters; D004361:Drug Tolerance; D005283:Fentanyl / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007278:Injections, Spinal / Q000009:adverse effects*; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D009994:Osmolar Concentration; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl