Modulatory influences on antegrade and retrograde tonic reflexes in the colon and rectum

Clinton Ng, Mark Danta, Gillian Prott, Caro-Anne Badcock, John Kellow, and Allison Malcolm

Gastrointestinal Investigation Unit, Royal North Shore Hospital, University of Sydney, St. Leonards, New South Wales 2065, Australia

Submitted 29 October 2003 ; accepted in final form 25 May 2004


    ABSTRACT
 TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Tonic reflexes in the colon and rectum are likely to be important in health and in disorders of gastrointestinal function. The aim of this study was to evaluate the fasting and postprandial "colorectal" and "rectocolic" reflexes in response to 2-min isobaric distensions of the colon and rectum, accounting for enteric sensation, compliance, and distending balloon volume. In 14 healthy fasting subjects, a dual barostat assembly was positioned (descending colon and rectum). A 2-min phasic distension was performed in the colon and rectum in random order while the opposing balloon volume was recorded. Sensation (phasic distension) and compliance (ramp distension) were also determined. The experiment was repeated postprandially. Colonic distension resulted in significant rectal tonic contraction in the fasting (rectal volume change: –35.4 ± 8.4 ml, P < 0.01) and postprandial (–22.2 ± 8.4 ml, P < 0.01) states. After adjustment for colonic sensitivity, for compliance, and for distending balloon volume, the rectal volume change remained significant; the extent of the tonic response, however, correlated significantly with increasing pain score (P < 0.01). In contrast, rectal distension did not produce a significant tonic response in the colon (fasting: –6.5 ± 7.3 ml; postprandial: 2.7 ± 7.3 ml), either unadjusted or adjusted for rectal sensitivity, compliance, and distending balloon volume. In conclusion, the colorectal reflex, but not the rectocolic reflex, can be readily demonstrated both before and after a meal in response to a 2-min isobaric distension in the colon and rectum, respectively. Although the presence of the colorectal reflex does not depend on colonic sensitivity or the volume of the distending colonic balloon, these factors modulate the reflex, especially in the fasting state.

enteric reflexes; tone; sensitivity; colorectum


THE ADVENT OF BAROSTAT TECHNOLOGY has enabled better characterization of the long intestinointestinal tonic reflexes present in both the small and large bowel. In the small bowel, antegrade and retrograde tonic inhibition occurs in response to mechanical distension within the jejunum (12); such reflexes are believed to be mediated by the sympathetic nervous system (7). In the large bowel, Law et al. (8) recently reported that colonic dilatation occurs in response to a series of three phasic rectal distensions and a staircase rectal distension (rectocolic reflex). In contrast, some degree of rectal contraction occurred in response to the corresponding series of colonic distensions, but only at a high phasic distension pressure of 32 mmHg above the individual operating pressure.

Law et al. (8), however, did not take into consideration possible local sensory and motor factors that may have influenced such responses. It is feasible that individual differences in, for example, sensitivity may influence the reflex response observed and may also affect the postprandial reflex response. Furthermore, Law et al. studied the reflexes only in the fasting state. It would seem important to study the reflex responses in the postprandial state as there are differences between the colorectal motor pattern between fasting and postprandial states, in particular increased colonic and rectal tone and increased contractile activity postprandially (1, 5, 13). In addition, patients with bowel disorders such as irritable bowel syndrome may experience exacerbation of symptoms after a meal, which may be contributed to by enteric reflex alterations. Our aims, therefore, were to extend the previous studies of colorectal tonic reflex interactions by 1) further characterizing the presence and nature of the descending "colorectal" and the ascending "rectocolic" tonic reflexes using a different distension paradigm; 2) determining the contributions of enteric sensation, compliance, and distending balloon volume to these reflexes; and 3) comparing the features of these reflexes in both the fasting and postprandial states.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Design, setting, and participants. Fourteen healthy subjects (11 females, mean age ± SE, 41 ± 3.6 yr) were recruited by public advertisement. All subjects completed the Rome II Integrative Questionnaire (4) and the Hospital Anxiety and Depression Scale (18). Exclusion criteria included previous bowel surgery, significant concurrent medical conditions, use of medications that may alter gastrointestinal motor and sensory function, the presence of symptoms consistent with a functional gastrointestinal disorder on the Rome II questionnaire, and the presence of significant anxiety or depression on the Hospital Anxiety and Depression Scale (18). All women of child-bearing capacity recorded a negative urine human chorionic gonadotropin pregnancy test. The study protocol was approved by the Human Research Ethics Committee of the Royal North Shore Hospital, and written, informed consent was obtained from all subjects before commencement of the study.

After an overnight fast and bowel cleansing with 2 liters of polyethylene glycol solution (Colonlytely, Dendy Pharmaceuticals, Brighton, Victoria, Australia), a dual-barostat assembly (Distender Series ll, G & J Electronics, Toronto, Canada), as described previously (10), was positioned with left-sided colonoscopy in the unsedated subjects. Polyethylene balloons (Hefty Baggies, Mobil Chemical, Pittsford, NY) with infinite compliance were positioned in the descending colon and rectum.

After a rest period, the individual operating pressure (IOP) was determined. A slow ramp (stepwise) distension (2 mmHg/30 s) was then performed in each region in random order until pain was reported by the subject. Colonic and rectal tone, as reflected by the balloon volume in the opposing region, were recorded continuously. After the ramp distension and a period of stabilization of balloon volumes, 2-min phasic distension, 20 mmHg above IOP, was performed, in random order, in both the colon and rectum. At the midpoint of the distension period, subjects completed a 10-cm visual analog scale (VAS) evaluating symptoms of gas, urgency, and pain. The symptom VAS was anchored by 0 for absence of symptom and 10 for maximum symptoms. The aggregate sensory score (ASS) was determined from the sum of gas, urgency, and pain derived from the VAS, providing a maximum score of 30 (11).

The distension sequence was then followed by a rest period of 30 min and ingestion of a standard 1,000-kcal (53% fat, 35% carbohydrate, 12% protein) liquid meal. A further period of 60 min was followed by a second distension sequence, as in the fasting phase.

Data and statistical analysis. Three time periods, predistension, distension, and postdistension, each of 2-min duration, were defined for each state, fasting and postprandial. The barostat volume response in the opposing balloon during the distension period was calculated as the difference between the mean volume during the predistension period and the mean volume during the 90–120 s of the distension period. The volume response during the postdistension period was calculated as the difference between the predistension mean volume and the mean volume during the 30–60 s of the postdistension period. The colorectal reflex was defined as the rectal tonic response (as measured by rectal volume change) to colonic distension. The rectocolic reflex was defined as the colonic tonic response (colonic volume change) to rectal distension. Compliance was determined from the slope of the pressure-volume curve during the ramp distension.

Generalized linear models were fitted to barostat volume responses within each time period during the fasting and postprandial states to cater for the paired nature of responses between the fasting and postprandial states and to adjust for sensation, compliance, and distending balloon volume. A generalized linear mixed model using an identity link function was used (y = Xa + Z{beta} + e). The design matrix for the fixed effects (X) included the overall mean period (that is fasting or postprandial). The period effect was adjusted for other measures such as sensation, compliance, and distending balloon volume by the use of covariates. Thus the fixed effects also included any covariates such as sensation, compliance, and distending balloon volume and the interaction between period and covariate. Results are presented for adjusted (least squares) means. The random effects (Z) included "subject" to take into account correlation responses within each subject. A reflex was identified if the mean barostat volume response was significant at P < 0.05, and a difference between states was declared if the comparison was also significant at P < 0.05.


    RESULTS
 TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Subject characteristics. The mean IOP (±SE) was 13.4 ± 2.8 mmHg for the colonic balloon and 9.1 ± 2.0 mmHg for the rectal balloon. The sensory measurements (ASS and pain score), the compliance and the volume of the distending balloon are shown in Table 1. In the colon, the sensation scores during balloon distension, the compliance, and the change in balloon volume were not different between the fasting and postprandial states. In the rectum, however, the ASS and the change in balloon volume during the distension were greater postprandially than during fasting. Rectal pain scores and rectal compliance were similar between the fasting and postprandial states.


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Table 1. Sensation, compliance, and distending balloon volume in the colon and rectum

 
Colorectal reflex. Colonic distension produced rectal contraction or an increase in rectal tone (see Fig. 1). Figure 2 shows the volumes in the rectal balloon before, during, and after colonic distension for both the fasting and postprandial states. The predistension volume in the rectal balloon was smaller postprandially (88.5 ± 19.7 ml) compared with the fasting predistension rectal volume (140 ± 15.6 ml, P = 0.01). There was a significant reduction in rectal balloon volume between the predistension volume and the volume during colonic distension in both the fasting (–35.4 ± 7.6 ml, P < 0.01) and postprandial (–22.2 ± 7.6 ml, P < 0.01) states. Postdistension, the rectal volume change was only significant in the fasting state (–27.2 ± 6.6 ml, P < 0.01). The magnitude of the reflex during the distension was not statistically different between the fasting and postprandial states. However, in the postdistension period, the change in rectal balloon volume was smaller postprandially (P = 0.04) compared with the fasting state.



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Fig. 1. Colorectal reflex: tracing from a study subject showing rectal contraction in response to a 2-min isobaric phasic colonic distension 20 mmHg above individual operating pressure (IOP).

 


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Fig. 2. Colorectal reflex: absolute rectal volumes (±SE) before (predistension), during, and after colonic balloon distension (postdistension) fasting and postprandially.

 
Colorectal reflex adjusted for sensation, compliance, and distending balloon volume. Table 2 shows the rectal volume change in response to colonic distension adjusted for pain score, overall sensation as measured by the ASS, volume change in the distending colonic balloon, and the colonic compliance. The rectal volume response (compared with predistension rectal volume) to colonic distension remained significant in both the fasting and postprandial periods during the distension with each of these adjustments.


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Table 2. Colorectal reflex (mean rectal volume) adjusted for sensation, distending balloon volume, and compliance

 
In the fasting state, a significant relationship was demonstrated between the change in distending colonic balloon volume and the rectal volume response during distension (r = –0.8, P = 0.001, Fig. 3A) and postdistension (r = –0.6, P = 0.02, data not shown) periods. The magnitude of the rectal contraction increased with the volume of the distending balloon both during the distension and postdistension periods. Postprandially, no significant relationship between distending balloon volume and rectal response was seen during the distension (Fig. 3B) or postdistension periods, as in the unadjusted analysis.



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Fig. 3. Rectal volume response correlated with change in distending colonic balloon volume during fasting (A) and postprandially (B).

 
The rectal volume response was also significantly related to pain score during distension (r = –0.6, P = 0.02, Fig. 4A) and postdistension (r = –0.6, P = 0.02, data not shown). Thus in the fasting state, with increasing pain scores, there was a greater rectal response. Again postprandially, no such relationship was seen during the distension (Fig. 4B) or postdistension periods.



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Fig. 4. Rectal volume response correlated with pain score during fasting (A) and postprandially (B).

 
Rectocolic reflex. The predistension colonic volumes in the fasting (135 ± 10.2 ml) and postprandial (121 ± 24.7 ml, P = 0.5) states were similar. The rectocolic reflex, as measured by the volume change in the colonic barostat balloon in response to rectal distension compared with the predistension colonic volume, was not significant (fasting –6.5 ± 7.3 ml; postprandial –2.7 ± 7.3 ml, P = NS). However, 7 of the 14 subjects did exhibit definite colonic dilatation in response to rectal distension (see Fig. 5), while there was no change or a reduction in the colonic volume in the other 7 subjects. Moreover, the colonic volume change was not different between the fasting and postprandial state.



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Fig. 5. Rectocolic reflex: tracing from a study subject showing colonic dilatation in response to a 2-min isobaric phasic rectal distension 20 mmHg above operating pressure.

 
Rectocolic reflex adjusted for sensation, compliance, and distending balloon volume. Table 3 shows the colonic volume change in response to rectal distension adjusted for pain score, ASS, volume change in the distending rectal balloon, and rectal compliance. There remained no significant colonic volume change in response to rectal distension with each of these adjustments and no difference between the fasting and postprandial states. However, similar to the colorectal reflex, the colonic volume change during rectal distension in the fasting phase was significantly related to the pain score. With increasing pain scores, the rectal volume change reverted from a positive to a negative value (slope= –15.8, P = 0.006). With each increase of pain score of 1, the volume change reduced by 15.8 ml (P = 0.006). Fasting and postprandial data were significantly correlated (P < 0.0001).


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Table 3. Rectocolic reflex (mean rectal volume) adjusted for sensation, distending balloon volume, and compliance

 

    DISCUSSION
 TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The novel findings from this study, using sophisticated dual-barostat technology, were that an isobaric colonic distension of 2-min duration was able to elicit a definite rectal contraction and that this response was present postprandially as well as in the fasting state. Moreover, after statistical adjustment for the inherent variability in local mechanical sensitivity at the site of the colonic distension, in colonic compliance, as well as in the actual distending volume of the colonic balloon, this response was preserved, supporting the concept that it represents a true reflex phenomenon, namely, the colorectal reflex. With respect to the corresponding rectocolic reflex, however, the same distension paradigm undertaken in the rectum did not elicit as consistent a colonic dilatation response.

Our findings are therefore on the one hand more definitive in regard to the colorectal reflex than those of Law et al. (8), but on the other hand less consistent in regard to the rectocolic reflex. These discrepancies may be related to differences in the study methodology and design, in particular, to the pressure level and the duration of the barostat distension employed. Law et al. were only able to demonstrate the colorectal reflex when they employed a phasic distending pressure, which was considerably higher (32 mmHg above operating pressure) than that in our current study. Indeed a distending pressure of 32 mmHg above IOP is considered to be the maximum safe level of distension for barostat studies. These investigators also utilized a 1-min duration distension rather than the longer 2-min distension employed in our study. The effects of varying levels and duration of distension thus seem worthy of further study. It is perhaps not surprising that the two reflexes that we evaluated are not triggered to a similar degree or extent by the one distension protocol. Lynn et al. (9) have recently shown that the rectum receives a different afferent innervation from that of the colon. Thus a distinct population of low-threshold, slow-adapting mechanoreceptors can be identified within specialized intraganglionic terminal endings in the rectum but not in the colon.

The colorectal reflex was still demonstrable postprandially, and the rectocolic reflex remained absent in the postprandial period. This was somewhat surprising given the known differences in motor function in the postprandial state compared with fasting state. Some individual differences were seen comparing fasting and postprandially, but this was not consistent across both reflexes (for example, there was a greater change in rectal balloon volume during the rectal distension, see Table 1). This may be due to a smaller predistension rectal volume postprandially, as a manifestation of the gastrorectal response, yet a similar volume was attained during the distension. However, a similar finding was not seen in the colon during colonic distension perhaps due to hysteresis that is known to occur after phasic distension (15) or due to regional differences in the colon and rectum, similar to the different responses seen when comparing other regions of the colon shown by Ford et al. (5).

The neural pathways involved in the rectocolic reflex are likely to involve extrinsic sympathetic pathways (8), similar to the inhibitory intestinointestinal reflexes in the small intestine (12), where there is either a prevertebral ganglion or spinal relay. Descending inhibitory inputs may modulate this reflex. The neural pathways involved in the colorectal reflex are less apparent but are likely to have some similarities to other "long" reflexes, including the descending gastrocolic reflex, where a variety of neuropeptide mediators, receptors, and pathways have been implicated (2, 11, 16). The exact neural pathways for both reflexes are, however, yet to be precisely defined and require further studies.

The other important aspect of our study was the preservation of the colonic response after correction for enteric sensitivity and compliance. Notwithstanding this preservation of the colorectal reflex, however, a greater rectal contraction occurred with greater pain perception of the colonic distension and also with a greater colonic distending volume (Figs. 3A and 4A). These findings, which were limited to the fasting state, indicate that local sensory and mechanical factors are modulatory influences on the colorectal reflex. The absence of a greater rectal response with a greater distending colonic balloon volume and pain postprandially (Figs. 3B and 4B) may be due to a complex interaction of neural and hormonal factors occurring as part of the gastrocolonic response. However, interestingly, a similar correlation between pain score and colonic response was apparent for the colonic responses to rectal distension (rectocolic reflex) in the fasting state despite the fact that a specific reflex was not uniformly demonstrable using the same distension paradigm. This lends support to the hypothesis that sensory factors modulate these reflex responses. Although both colonic and rectal compliance were not significantly altered after the meal, we found that, as in animal studies, rectal sensitivity as determined by the rectal ASS was increased postprandially (Table 1). Although other studies have reported an increased ASS with rectal distension in irritable bowel syndrome patients postprandially (3, 17), our data indicate that even healthy subjects can exhibit an increased ASS with rectal distension postprandially. This postprandial hypersensitivity may explain the lack of correlation between rectal volume response and pain in the postprandial period. Our study does not enable elucidation of whether the modulatory influence of sensation is primarily enteric or central in origin, although because it was especially prominent with respect to pain, a central component seems reasonable to assume (14).

The functional significance of both the rectocolic and the colorectal reflex in health is largely unknown. The rectocolic response may represent a compensatory response to avoid overfilling of the rectum particularly when the rectum is suddenly filled (8), whereas the colorectal reflex may be important as preparation for the defecatory process (6). It is conceivable that even subtle alterations in these responses may be a precipitant of symptoms in some patients with functional gastrointestinal disorders.

In conclusion, the colorectal tonic reflex was clearly demonstrable when a 2-min isobaric colonic distension was employed. Local pain sensitivity and the distending colonic volume were, however, important factors modulating the colorectal reflex. These factors need to be taken into account when evaluating the reflex in various gastrointestinal disorders, particularly in disorders where enteric pain sensitivity itself may be abnormal.


    ACKNOWLEDGMENTS
 
C. Ng was supported by a National Health and Medical Research Council (Australia) scholarship.


    FOOTNOTES
 

Address for reprint requests and other correspondence: A. Malcolm, Dept. of Gastroenterology, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia (E-mail: amalcolm{at}med.usyd.edu.au)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


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 RESULTS
 DISCUSSION
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