title: Anterior cingulate cortex modulates visceral pain as measured by visceromotor responses in viscerally hypersensitive rats.
abstract: OBJECTIVE
  We have identified that the anterior cingulate cortex (ACC) neurons are responsive to colorectal distention (CRD) and shown that sensitization of ACC neurons occurs in viscerally hypersensitive rats. However, the role of the ACC in pain response has not been clearly defined. We aimed to determine if ACC neuron activation enhances visceral pain in viscerally hypersensitive rats and to identify the receptor involved in facilitation of visceral pain.
  
  
  METHODS
  The nociceptive response (visceromotor response [VMR]) to CRD was recorded in normal and viscerally hypersensitive rats induced by colonic anaphylaxis. The ACC was stimulated electrically, and ACC lesions were generated with ibotenic acid. l-glutamate, alpha-amino-3-hydroxy-5-methyl-isoxozole propionic acid receptor antagonist cyanonitroquinoxaline dione, and N-methyl-d-aspartate receptor antagonist aminophosphonopentanoic acid were microinjected into the rostral ACC.
  
  
  RESULTS
  Electrical stimulation of the rostral ACC enhanced the VMR to CRD in normal rats. ACC lesions caused a decrease in the VMR in viscerally hypersensitive rats but had no effect in normal rats. ACC microinjection of 2 mmol/L glutamate increased the VMR to CRD (10 mm Hg) in viscerally hypersensitive rats, and 20 mmol/L glutamate induced a more potent VMR in viscerally hypersensitive than in normal rats. Cyanonitroquinoxaline dione did not affect the VMR in either group. Aminophosphonopentanoic acid significantly suppressed the VMR in viscerally hypersensitive rats but not in normal rats.
  
  
  CONCLUSIONS
  The ACC plays a critical role in the modulation of visceral pain responses in viscerally hypersensitive rats. This process appears to be mediated by enhanced activities of glutamate N-methyl-d-aspartate receptors.
authors.affiliation: Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Cao
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Wu
authors.forename: Shengliang
authors.initials: S
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Fan
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Chung
authors.initials: C
authors.lastname: Owyang
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
mesh_terms: D000418:Albumins / Q000009:adverse effects; D000707:Anaphylaxis / Q000139:chemically induced / Q000503:physiopathology; D000818:Animals; D003106:Colon / Q000503:physiopathology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D018698:Glutamic Acid / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000502:physiology*; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology; D014781:Viscera / Q000294:innervation* / Q000503:physiopathology*
chemical_list: D000418:Albumins; D011810:Quinoxalines; D017470:Receptors, Glutamate; D018698:Glutamic Acid; C056723:FG 9041