The neurological safety of epidural pamidronate in rats.
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.
Lee
Pyung Bok
PB
Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul, Korea.
Kim
Yong Chul
YC
Lee
Chul Joong
CJ
Shin
Hye Young
HY
Lee
Seung Yun
SY
Park
Jong Cook
JC
Choi
Yun Suk
YS
Kim
Chong Soo
CS
Park
Sang Hyun
SH