Intracolonic zymosan produces visceral hyperalgesia in the rat that is mediated by spinal NMDA and non-NMDA receptors.
The present study examined the effects of colonic inflammation on reflex responses to colorectal distension (CRD) in awake rats. Visceromotor responses (VMR) to CRD were recorded in rats that received either no treatment or intracolonic saline or zymosan. Three hours following zymosan treatment (25 mg/ml; 1 ml) VMR response magnitudes were significantly increased at all intensities of CRD tested (10-80 mmHg). The enhanced responses to CRD were attenuated in a dose-dependent fashion by intrathecal administration of the non-competitive N-methyl-D-aspartate (NMDA) receptor channel blocker MK-801 to 60% of control and by the non-NMDA receptor antagonist DNQX to less than 20% of control. The metabotropic receptor antagonist AP-3 was without effect. Signs of multi-focal colonic inflammation were clearly present 3 h after zymosan treatment, characterized by an ingress of inflammatory cells and damaged crypts in and around these foci. Taken together these findings suggest that tissue inflammation increases the sensitivity of the colon to mechanical stimuli, leading to enhanced responses to CRD. This enhancement involves the activation of spinal NMDA as well as non-NMDA receptors, but not metabotropic receptors.
Coutinho
S V
SV
Department of Pharmacology, University of Iowa, Iowa City 52242, USA.
Meller
S T
ST
Gebhart
G F
GF
D000818:Animals; D003106:Colon / Q000294:innervation / Q000473:pathology / Q000503:physiopathology*; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006930:Hyperalgesia / Q000503:physiopathology*; D007249:Inflammation; D007278:Injections, Spinal; D008297:Male; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D015054:Zymosan / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C056723:FG 9041; D016291:Dizocilpine Maleate; D015054:Zymosan