Spinal neurotoxicity and tolerance after repeated intrathecal administration of YM 872, an AMPA receptor antagonist, in rats.
OBJECTIVE
Although the Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, YM 872, has been considered to be useful in analgesia for both acute and chronic pain, there are no studies of its neurotoxicity and tolerance. We examined the spinal neurotoxicity and tolerance of YM 872 analgesia by repeated intrathecal administration in rats.


METHODS
Male Sprague-Dawley rats with lumbar intrathecal catheters received YM 872 at 1 micro g. 10 micro l-1 (eight rats; YM group) or normal saline 10 micro l (eight rats; C group) intrathecally once a day for 30 days. We evaluated the analgesic effects every 3 days, by tail-flick test and behavioral side effects. On the 31st day, the lumbar spinal cord was removed from four randomly selected rats in each group for histological examination.


RESULTS
The YM group showed significantly longer tail-flick latency when subjected to a high-intensity light beam than the C group at each measurement time point, although no significant changes in the latency according to the time course of the study were observed for the entire study period of 30 days in either group. No rats showed any side effects. Histologically, only slight lymphocytic cell infiltration and degeneration of myelinated fibers occurred, similarly in both groups. No changes were observed in the spinal cord in either group.


CONCLUSIONS
Administration of YM 872 (1 micro g) once a day for 30 days did not induce any tolerance and caused no histological changes in the spinal cord.
Nishiyama
Tomoki
T
Department of Anesthesiology, The University of Tokyo, Japan.
Kawasaki-Yatsugi
Sachiko
S
Yamaguchi
Tokio
T
Hanaoka
Kazuo
K
D000700:Analgesics / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004361:Drug Tolerance; D007093:Imidazoles / Q000008:administration & dosage / Q000633:toxicity*; D007278:Injections, Spinal; D008297:Male; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D011810:Quinoxalines / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology; D013623:Tail
D000700:Analgesics; D007093:Imidazoles; D011810:Quinoxalines; D018091:Receptors, AMPA; C110629:YM 872