Enhanced responses of the anterior cingulate cortex neurones to colonic distension in viscerally hypersensitive rats.
The anterior cingulate cortex (ACC) is critically involved in processing the affective component of pain sensation. Visceral hypersensitivity is a characteristic of irritable bowel syndrome. Electrophysiological activity of the ACC with regard to visceral sensitization has not been characterized. Single ACC neuronal activities in response to colorectal distension (CRD) were recorded in control, sham-treated rats and viscerally hypersensitive (EA) rats (induced by chicken egg albumin injection, i.p). The ACC neurones of controls failed to respond to 10 or 30 mmHg CRD; only 22% were activated by 50 mmHg CRD. Among the latter, 16.4% exhibited an excitatory response to CRD and were labelled 'CRD-excited' neurones. In contrast, CRD (10, 30 and 50 mmHg) markedly increased ACC neuronal responses of EA rats (10%, 28% and 47%, respectively). CRD produced greater pressure-dependent increases in ACC spike firing rates in EA rats compared with controls. Splanchnicectomy combined with pelvic nerve section abolished ACC responses to CRD in EA rats. Spontaneous activity in CRD-excited ACC neurones was significantly higher in EA rats than in controls. CRD-excited ACC neurones in control and EA rats (7 of 16 (42%) and 8 of 20 (40%), respectively) were activated by transcutaneous electrical and thermal stimuli. However, ACC neuronal activity evoked by noxious cutaneous stimuli did not change significantly in EA rats. This study identifies CRD-responsive neurones in the ACC and establishes for the first time that persistence of a heightened visceral afferent nociceptive input to the ACC induces ACC sensitization, characterized by increased spontaneous activity of CRD-excited neurones, decreased CRD pressure threshold, and increased response magnitude. Enhanced ACC nociceptive transmission in viscerally hypersensitive rats is restricted to visceral afferent input.
Gao
Jun
J
Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, 6510 Medical Sciences Research Building I, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0682, USA.
Wu
Xiaoyin
X
Owyang
Chung
C
Li
Ying
Y
D000418:Albumins; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D003106:Colon / Q000294:innervation*; D004195:Disease Models, Animal; D021181:Egg Hypersensitivity; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D043183:Irritable Bowel Syndrome / Q000503:physiopathology*; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013153:Splanchnic Nerves / Q000502:physiology; D013696:Temperature; D004561:Transcutaneous Electric Nerve Stimulation
D000418:Albumins