title: The neurological safety of epidural pamidronate in rats.
abstract: BACKGROUND
  Pamidronate is a potent inhibitor of osteoclast-mediated bone resorption. Recently, the drug has been known to relieve bone pain. We hypothesized that direct epidural administration of pamidronate could have various advantages over oral administration with respect to dosage, side effects, and efficacy. Therefore, we evaluated the neuronal safety of epidurally-administered pamidronate.
  
  
  METHODS
  Twenty-seven rats weighing 250-350 g were equally divided into 3 groups. Each group received an epidural administration with either 0.3 ml (3.75 mg) of pamidronate (group P), 0.3 ml of 40% alcohol (group A), or 0.3 ml of normal saline (group N). A Pinch-toe test, motor function evaluation, and histopathologic examination of the spinal cord to detect conditions such as chromatolysis, meningeal inflammation, and neuritis, were performed on the 2nd, 7th, and 21st day following administration of each drug.
  
  
  RESULTS
  All rats in group A showed an abnormal response to the pinch-toe test and decreased motor function during the entire evaluation period. Abnormal histopathologic findings, including neuritis and meningeal inflammation were observed only in group A rats. Rats in group P, with the exception of 1, and group N showed no significant sensory/motor dysfunction over a 3-week observation period. No histopathologic changes were observed in groups P and N.
  
  
  CONCLUSIONS
  Direct epidural injection of pamidronate (about 12.5 mg/kg) showed no neurotoxic evidence in terms of sensory/motor function evaluation and histopathologic examination.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Pyung Bok
authors.initials: PB
authors.lastname: Lee
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Chul Joong
authors.initials: CJ
authors.lastname: Lee
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Shin
authors.forename: Seung Yun
authors.initials: SY
authors.lastname: Lee
authors.forename: Jong Cook
authors.initials: JC
authors.lastname: Park
authors.forename: Yun Suk
authors.initials: YS
authors.lastname: Choi
authors.forename: Chong Soo
authors.initials: CS
authors.lastname: Kim
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Park