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NEUROREGULATION AND MOTILITY

Role for NMDA receptors in visceral nociceptive transmission in the anterior cingulate cortex of viscerally hypersensitive rats

Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan

Submitted 3 October 2007 ; accepted in final form 31 January 2008

We have identified colorectal distension (CRD)-responsive neurons in the anterior cingulate cortex (ACC) and demonstrated that persistence of a heightened visceral afferent nociceptive input to the ACC induces ACC sensitization. In the present study, we confirmed that rostral ACC neurons of sensitized rats [induced by chicken egg albumin (EA)] exhibit enhanced spike responses to CRD. Simultaneous in vivo recording and reverse microdialysis of single ACC neurons showed that a low dose of glutamate (50 µM) did not change basal ACC neuronal firing in normal rats but increased ACC neuronal firing in EA rats from 18 ± 2 to 32 ± 3.8 impulses/10 s. A high dose of glutamate (500 µM) produced 1.95-fold and a 4.27-fold increases of ACC neuronal firing in sham-treated rats and in EA rats, respectively, suggesting enhanced glutamatergic transmission in the ACC neurons of EA rats. Reverse microdialysis of the 3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainite receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 µM) reduced basal and abolished CRD-induced ACC neuronal firing in normal rats. In contrast, microdialysis of N-methyl-D-aspartate (NMDA) receptor antagonist AP5 had no effect on ACC neuronal firing in normal rats. However, AP5 produced 86% inhibition of ACC neuronal firing evoked by 50 mmHg CRD in the EA rats. In conclusion, ACC nociceptive transmissions are mediated by glutamate AMPA receptors in the control rats. ACC responses to CRD are enhanced in viscerally hypersensitive rats. The enhancement of excitatory glutamatergic transmission in the ACC appears to mediate this response. Furthermore, NMDA receptors mediate ACC synaptic responses after the induction of visceral hypersensitivity.

anterior cingulate cortex; visceral hypersensitivity; NMDA and non-NMDA receptors

This article has been cited by other articles:

				S. L. Chen, X. Y. Wu, Z. J. Cao, J. Fan, M. Wang, C. Owyang, and Y. Li Subdiaphragmatic vagal afferent nerves modulate visceral pain Am J Physiol Gastrointest Liver Physiol, June 1, 2008; 294(6): G1441 - G1449. [Abstract] [Full Text] [PDF]