Regional difference in colonic motility response to electrical field stimulation in Guinea pig

Abstract

Background/aims: In isolated guinea-pig colon, we investigated regional differences in peristalsis evoked by intrinsic electrical nerve stimulation.

Methods: Four colonic segments from mid and distal colon of Hartley guinea pigs, were mounted horizontally in an organ bath. Measurement of pellet propulsion time, intraluminal pressure, electrical field stimulation (EFS; 0.5 ms, 60 V, 10 Hz), and response of pharmacological antagonists, were performed to isolated segments of colon to determine the mechanisms underlying peristaltic reflexes evoked by focal electrical nerve stimuli.

Results: In fecal pellet propulsion study, the velocity of pellet propulsion was significantly faster in the distal colon and decreased gradually to the proximal part of the mid colon. Intraluminal pressure recording studies showed that luminal infusion initiated normal peristaltic contractions (PCs) in 82% trials of the distal colon, compared to that of mid colon. In response to EFS, the incidence of PCs was significantly increased in the distal colon in contrast, the incidence of non-peristaltic contractions (NPCs) was significantly higher in the middle-mid colon, distal-mid colon and distal colon, compared to that of proximal-mid colon. Addition of L-NAME into the bath increased the frequency of NPCs. EFS failed to cause any PCs or NPCs contractions in the presence of hexamethonium, atropine or tetrodotoxin.

Conclusions: This study has revealed that electrical nerve stimulation of distal colon is the most likely region to elicit a peristaltic wave, compared with the mid or proximal colon. Our findings suggest that EFS-evoked PCs can be modulated by endogenous nitric oxide.

Keywords: Anti-peristalsis; Colonic transit; Nitric oxide.

Figure 1

Gross anatomy of the guinea pig colon (A) and regional differences of fecal pellet propulsion among of the 4 different segments (B). The velocity of pellet propulsion was significantly higher in the distal colon and reduced at the proximal part of the mid colon. MC, mid colon; DC, distal colon. ^*P < 0.05 vs. DC, ^**P < 0.05 vs. distal-MC, n = 5.

Figure 2

Intraluminal pressure increase and motor responses to luminal distension of the distal colon. In response to luminal infusion (0.3 mL), pressure increase was observed in the distal colon. The incidence of peristaltic contractions (PCs; 81.5 ± 7.0%, n = 6) was higher than that of non-peristaltic contractions (NPCs; 18.5 ± 7.0%, n = 6). Vertical arrows indicate NPCs, while horizontal arrows indicate PCs.

Figure 3

Regional differences of motility patterns in response to luminal distension. Motor responses of the proximal portion of the mid colon (A), middle portion of the mid colon (B), distal portion of the mid colon (C) and distal colon (D) are shown. The proximal-mid colon showed frequent phasic contractions (A), while the middle-mid colon showed a mixed pattern of phasic contractions, non-peristaltic contractions (NPCs) and peristaltic contractions (PCs) (B). The distal-mid colon and distal colon showed regular and frequent PCs with less incidence of NPCs (C and D).

Figure 4

Responses to electrical field stimulation (EFS) applied at the oral end during the luminal distension in the guinea pig colonic segments. When EFS was applied after spontaneous peristaltic contraction (PC), EFS evoked PCs especially at the distal-mid colon and distal colon (C and D). In response to EFS, a significant increase of luminal pressure concomitant with PC was observed in 74.7% trials in the distal colon (D and E). The incidence of non-peristaltic contractions (NPCs) and no responses were observed in 13.7% and 11.7%, respectively, of the distal colon (48 studies of 6 tissues). The incidence of PCs was significantly increased in the distal colon, compared to that of the proximal-mid colon. In contrast, the incidence of NPCs was significantly lower in the middle-mid colon, distal-mid colon and distal colon, compared to that of proximal-mid colon (E) (45-60 studies of 6 tissues). Arrows indicate applications of EFS. MC, mid colon; DC, distal colon. ^*P < 0.05, ^**P < 0.01 vs. proximal-mid colon.

Figure 5

Responses to electrical field stimulation (EFS) at the oral and anal end of the distal colon. EFS-induced peristaltic contractions (PCs) were always oral-to-anal direction regardless of stimulation point and the mean amplitude was not significantly different between both stimulation points (A). Orally applied EFS tended to increase the incidence of PCs more than anally applied EFS (P = 0.06). The incidence of NPCs was significantly higher in response to anally applied EFS than orally applied EFS (B) (^*P < 0.05 vs. oral-EFS, n = 5). NPCs, non-peristaltic contractions.

Figure 6

Responses to electrical field stimulation (EFS) at the oral and anal end of the distal colon in the presence of neural blocking agents. Administration of NG-nitro-L-arginine methyl ester (L-NAME) itself increased the incidence of non-peristaltic contractions (NPCs) to 70%. When EFS was applied to the oral or anal end of the colon, non-coordinated NPCs were observed in the distal colon in the presence of L-NAME (A) (Video 3). In the presence of hexamethonium, atropine and and tetrodotoxin, intraluminal pressure increase in response to luminal infusion was no longer observed. Hexamethonium, atropine and TTX completely abolished the responses to EFS (B-D) (n = 6 in each group). O, oral end; A, anal end.