Proximal colon distension induces Fos expression in the brain and inhibits gastric emptying through capsaicin-sensitive pathways in conscious rats.
We assessed brain nuclei activated during noxious mechanical distension of the proximal colon in conscious rats, using Fos as a marker of neuronal activation, and functional reflex changes in gastric emptying associated to colon distension. The role of capsaicin-sensitive afferents in Fos and gastric responses to distension was also investigated. Compared with sham distension, isovolumetric phasic distension of the proximal colon (10 ml, 30 s on/off for 10 min) increased significantly Fos expression 1 h after distension in selective brain areas, most prominently, the paraventricular and supraoptic nuclei of the hypothalamus (13-fold and 80-fold, respectively), the locus coeruleus-Barrington's nucleus complex (2-fold), area postrema (7-fold) and the nucleus tractus solitarius (4-fold). Increased Fos expression was also observed in the cingulate cortex, posterior paraventricular nucleus of the thalamus, periaqueductal gray and ventrolateral medulla. Distension of the proximal colon significantly inhibited gastric emptying by 82% and 34%, as measured 30 and 60 min after the distension respectively, compared with control. Pretreatment with systemic capsaicin prevented both the brain increase in Fos expression and the inhibition of gastric emptying induced by the colon distension. These results show that visceral pain arising from the proximal colon activates a complex neuronal network that includes specific brain nuclei involved in the integration of autonomic, neuroendocrine and behavioral responses to pain and an inhibitory motor reflex in other gut areas (delayed gastric emptying). Capsaicin-sensitive afferent pathways are involved in mediating brain neuronal activation and functional changes associated with noxious visceral stimulation.
Martínez
Vicente
V
CURE: Digestive Diseases Research Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, and VA Greater Los Angeles Healthcare System, 90073, USA.
Wang
Lixin
L
Taché
Yvette
Y
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D003106:Colon / Q000033:anatomy & histology / Q000294:innervation* / Q000502:physiology; D005746:Gastric Emptying / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009434:Neural Pathways / Q000187:drug effects* / Q000502:physiology; D016761:Oncogene Proteins v-fos / Q000378:metabolism*; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D014851:Wakefulness / Q000502:physiology
D016761:Oncogene Proteins v-fos; D002211:Capsaicin