ABSTRACT
N-Methyl-d-aspartate (NMDA) is known to be involved in the transmission of nociceptive information. In the present study, we investigated the effect of peripheral and central NMDA receptor antagonist MK-801 in visceral hypersensitivity. In an animal model of colorectal distension (CRD), administration of both intrathecal MK-801 (1.5 nmol) and intraperitoneal MK-801 (0.15 mg/kg) completely abolished the CRD-induced visceral hypersensitivity of noxious and innocuous stimuli. Thus, the results from this experiment demonstrate the efficacy of MK-801 in blocking the visceral hypersensitivity mediated by central and peripheral mechanisms.
Subject(s)
Dizocilpine Maleate/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Hyperalgesia/physiopathology , Receptors, N-Methyl-D-Aspartate/physiology , Abdomen/physiology , Animals , Behavior, Animal/drug effects , Colon/physiology , Disease Models, Animal , Dizocilpine Maleate/administration & dosage , Excitatory Amino Acid Antagonists/administration & dosage , Injections, Intraperitoneal , Injections, Spinal , Male , Muscle Contraction/physiology , Physical Stimulation , Rats , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate/drug effects , Rectum/physiologyABSTRACT
Tachykinins are known to be involved in the processing of information leading to central sensitization and nociception. Using an animal model of repetitive colorectal distensions (CRD), we investigated the effect of spinal administration of tachykinin receptor antagonists in the mediation of visceral hypersensitivity. Intrathecal administration of the NK(1) receptor antagonist RP-67,580 (6.5 nmol) and the NK(3) receptor antagonist R-820 (6.5 nmol) completely blocked the CRD-induced hyperalgesia for both noxious and innocuous stimuli. The intrathecal administration of SR-48,968, a tachykinin NK(2) receptor antagonist, did not affect the visceral pain threshold of hypersensitive animals. Thus, the results from the present experiment support the concept that tachykinins with actions at spinal NK(1) and NK(3) but not NK(2) receptor sites are involved in visceral hypersensitivity mediated by nociceptive and non-nociceptive afferent inputs.
