The effects of an intrathecal NMDA antagonist (AP5) on the behavioral changes induced by colorectal inflammation with turpentine in rats.
Visceral pain, especially that associated with inflammation of visceral organs, is poorly understood and difficult to treat clinically. The purpose of this study was to investigate the effects of intrathecal 2-amino-5-phosphonovaleric acid (AP5, a competitive NMDA antagonist) upon a visceromotor response to distension of colonic tissue inflamed by exposure to turpentine. All experiments were conducted under pentobarbital anesthesia. Animals were prepared with a laminectomy from T12 to L1 to facilitate intrathecal drug administration. Colonic distension thresholds for a visceromotor response were determined in the presence and absence of AP5. Animals were divided into two groups. The NS group received 50 microl of saline intrathecally and the AP5 group 10 mM of AP5 in 50 microl saline. After baseline measurements, intrathecal drugs were administered. Five minutes later, the effects of intrathecal drugs were measured, then 1 ml of 25% turpentine was administered anorectally. Subsequent measurements were made every 5 minutes for the next 90 minutes. Visceromotor thresholds to colorectal distension (CRD) were significantly decreased 50 min after turpentine administration in the NS group. There was no threshold change in the AP5 group. This study suggests that the administration of the competitive NMDA receptor antagonist AP5 in this model blocks the effect of turpentine sensitization on visceromotor response to CRD. The absence of AP5 effects in animals not sensitized by turpentine suggests that NMDA systems may be involved in the sensitization.
Ide
Y
Y
Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Maehara
Y
Y
Tsukahara
S
S
Kitahata
L M
LM
Collins
J G
JG
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014425:Turpentine
D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D014425:Turpentine