motility disorders and stress

Digestive Diseases and Sciences, Vol. 34, No. 11 (November 1989), pp. 1777-1786

R E V I E W ARTICLE

Motility Disorders and Stress MICHAEL CAMILLERI, MD, and MATTEO NERI, MD

The association between emotion and gastrointestinal dysfunction has been postulated for centuries, and all practicing clinicians have anecdotal experience o f the association between stress and irritable bowel syndrome (IBS). However, definite proof o f an etiologic link between stress and gut motor dysfunction remains elusive, despite the large number of publications on this topic.

A critical appraisal o f methodology, use o f controls, data interpretation, and significance of findings in the published literature is necessary to assess the present state o f knowledge and to develop more meaningful studies in the future. This review attempts to summarize these perspectives.

KEY WORDS: functional gastrointestinal disease; irritable bowel syndrome; functional dyspepsia; stress; motility.

STRESS AND GUT DYSFUNCTION

Many attempts have been made over the years to find an abnormal intestinal motor pattern in patients with IBS, initially in the colon (1-8) and later in other regions of the gut (9-11). However, these studies have not provided conclusive evidence for a definite role of abnormal motor activity in the origin of this ailment. Some of the difficulties in establish- ing such an etiologic role include: the necessity for sufficient standardization and sophistication of motility recording techniques, appropriate patient se- lection and controls, and problems with experimental design. Epidemiologic studies (12) indicate that there is an association between the occurrence of stressful experiences and the appearance of disturbances in bowel function. The logical extension of these epidemiologic and clinical observations has been the application of stressful stimuli in an attempt to demonstrate a motility disorder in the IBS patients. Thus, some of the early elegant studies of

Manuscript received January 31, 1989; revised manuscript received June 12, 1989; accepted June 15, 1989.

From the Gastroenterology Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota 55905.

Dr. Neri's present address is: Istituto di Fisiopatologia Med- ica, Ospedale SS. Annunziata, 66100 Chieti, Italy.

Address for reprint requests: Dr. Michael Camilleri, Gastro- enterology Research Unit, Mayo Clinic, Rochester, Minnesota 55905.

Almy and coworkers (1, 2, 13) remain among the best examples of the potential of experimental psychologic or painful stress in inducing motor changes in the gut (Figure 1).

METHODOLOGIC DIFFICULTIES

There are many reasons why this line of investigation is difficult. The boundaries between normal- ity and IBS patients are not always clearly defined: epidemiologic studies demonstrated that a large number of subjects in an unselected population had symptoms of the IBS even though they never sought medical care for these symptoms (14, 15). In contrast, the specificity of motility patterns found in IBS patients is unclear; in fact, Kellow and Phillips (16) have reported that patients with IBS demonstrated pain-associated distal small intestinal motility patterns that also occur in asymptomatic individuals. There is also an immense variability in the motor patterns occurring among normal individuals (10, 17). Some motor patterns are infrequent (eg, phase III of MMC, prolonged propagated contractions) or not consistently recorded (colonic three per minute electrical control activity). Hence, these investigations tend to be prolonged, and it may be difficult to assess whether such motor patterns are induced by stress caused by the long studies, the underlying disorder, or other uncontrolled varia-

Digestive Diseases and Sciences, Vol. 34, No. 11 (November 1989)

0163-2116/89/1100-I777506.00/0 @ 1989 Plenum Publishing Corporation 1777

C A M I L L E R I A N D N E R I

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Fig 1. Effect of stressful interview on colonic motility in a healthy volunteer. The motility increases dramatically with mention of the possible lobotomy for her ill sister (B) when compared with baseline colonic motility (A). (Reproduced with permission from reference 13.)

bles. Furthermore, distinction of the IBS population from controls necessitates controlling for the psychoneurotic trait (18) in studies that evaluate the effect of stress on gut motor function.

While stress in everyday life would be more relevant in the study of IBS subjects, most studies have applied "acute" forms of stress in an attempt to define the pathophysiology of IBS. Different types of stress clearly elicit different responses. In the earlier studies of Wolf and Wolff (19) on their patient, Tom, the vascularity of the gastric fistula and the observed gastric motility were clearly de- pendent upon the nature of the stressful stimulus (fear or anger). Similarly, Cannon (20) noted that "rage, distress or mere anxiety was accompanied by a total cessation of the movements of the stomach" in the dog, while "fear occasioned more rapid movements." The variety of stressful stimuli used in such studies may be mediated by different afferent pathways and may reach different levels of the higher centers. Thus, whereas labyrinthine stimulation and dichotic listening (Appendix) both reach the nuclei of the eighth cranial nerve, they clearly stimulate different sensory organs, and the pathways along the cochlear and vestibular fibers synapse in different brain-stem nuclei. Whereas labyrinthine stimulation may induce gastrointestinal effects by connections between vestibular nuclei and efferent brain-stem nuclei to the gut, dichotic listening is likely to relay to centers higher than the brain-stem. With the general assumption that any

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form of stressful stimulation is appropriate to study the gut motor responses in healthy individuals and IBS patients, the potential importance of the path- way and centers mediating the effects has received little consideration.

Adaptation to the stressful stimulus may also contribute to the wide range of responses elicited on exposure to the same stimulus. This emphasizes the importance of randomization of the order of stress and nonstress periods during acute studies and of relating physiologic effects of stress to the particu- lar stimulus used (Table 1).

RELATIONSHIP BETWEEN ACUTE (EXPERIMENTAL) STRESS AND IRRITABLE

BOWEL SYNDROME

IBS is not a syndrome peculiar to stress, since in many IBS patients, stress does not appear to be a contributing factor. However, since stress often appears to provoke symptoms of IBS in a subset of patients, it has been used experimentally to induce measurable dysfunction in the gut. In appraising the relationships among stress, motility and IBS, we shall attempt to focus on three main questions: First, is there a consistent motility disturbance in IBS? Second, what are the effects of stress on motility in various regions of the gut in healthy and IBS subjects? Third, can acute (experimental) stress-evoked dysfunction be used to elucidate differences in motor activity between normals and IBS patients?

IS THERE A CONSISTENT MOTILITY DISTURBANCE IN IBS?

In this section, we summarize the reported disturbances of gut motility in patients with functional gastrointestinal disease (21) and categorize those features for each anatomic level from esophagus to colon.

Esophagus

A relationship between emotional state and esophageal motility was suggested by the observation of a high frequency (84%) of psychiatric abnormalities (predominantly depression or anxiety neu- rosis) among 25 individuals with dysphagia or noncardiac chest pain who had contraction abnormalities on esophageal manometry (22). Others (23) reported that IBS and nutcracker esophagus patients have greater gastrointestinal susceptibility and somatic anxiety than controls in the 150-item


STRESS AND MOTILITY IN IBS

TABLE 1. SUMMARY OF STUDIES ON MOTILITY AND STRESS IN IRRITABLE BOWEL SYNDROME (IBS) AND HEALTHY* SUBJECTS (H)

Author Year Type o f stress Subjects Fasting Fed Esophagus Stomach Small intestine Colon

Almy 1947 Interview H + + 1' amplitude Latimer 1981 Interview IBS, psycho- + No change

neurotics electrical activity

McRae 1982 DL H Thompson 1982, LS, CP H

1983

+

Cann 1983 DL H +

Stanghellini 1984 CP, LS H +

Camilleri 1984 TENS H + Kumar 1985 " m i x " Narducci 1985 CP, stroop test, H, IBS +

ball sorting Valori 1986 " m i x " + sleep H uncontrolled

interruption Richter 1986 Noise, cognitive Chest pain +

reasoning tasks Camilleri 1986 TENS H +

IBS + Cook 1987 DL H +

Schang 1988 CP H +

~' amplitude

~' LES pressure

MMC emptying of Phase III-like

liquid activity (LS only)

N-homogenized Faster transit solids

~, M1 Phase III-like activity (LS only)

MI J, MMC

~, daytime MMC, No ~ at night

~, MI No A or $ MI

1' MI

No change in electrical activity

*LS = labyrinthine stimulation; DL = dichotomous listening; CP = cold pain, " m i x " = mixture of video games, driving in heavy traffic, delayed audio feedback; TENS = transcutaneous electrical nerve stimulation; MI = motility index; H = healthy; MMC = interdigestive migrating motor complex; phase III-like activity = postprandial propagated activity front with frequency of contractions similar to interdigestive phase III; N-homogenized solids = normal emptying of homogenized solids; No A = no change.

self-reporting health inventory. Patients with a history of globus sensation were also more anxious, neurotic, and depressed than normal controls (24).

Stomach

The symptom complex of dyspepsia that is unas- sociated with biliary tract or ulcer disease, often referred to as functional dyspepsia, is considered a variant of the irritable bowel syndrome (21, 25). In such patients, postprandial antral motility may either be normal or suppressed (26). The two sub- groups of patients with functional dyspepsia could not be distinguished on the basis of their psychoneurotic traits or their autonomic and humoral responses to the stress. These data suggested that there is a subgroup of patients with the functional dyspepsia variant of the irritable bowel syndrome in whom there is abnormal motor function of the stomach even in the absence of stress. This observation was supported by the data of Jian et al (27) and Corinaldesi et al (28), who found that about 50% of their population of nonulcer dyspeptics also had impaired gastric emptying of solids. Similarly,

Digestive Diseases and Sciences, Val. 34, No. 11 (November 1989)

abnormal gastric myoelectrical activity was de- tected in 48% of a group of patients with unexplained nausea and vomiting (29). The other ap- proximately 50% of the patients with nonulcer dyspepsia develop symptoms on the basis of another pathophysiologic mechanism, and it has been postulated (26) that in this subgroup with normal baseline postprandial motility it is the abnormal perception of normal stress-induced motor changes that results in the development of symptoms.

Small Bowel

A wide variability in the periodicity and duration of phase III of the interdigestive migrating motor complex (MMC) has been noted in IBS patients by Kingham et al (10) and in health by Kerlin and Phillips (17). In the former study of small bowel motility for 30 consecutive hours in healthy volunteers and IBS patients, there were no differences in the characteristics including frequency of phase III or any of the other motor abnormalities sought.

In a prolonged small intestinal manometric study of 16 IBS patients, Kellow and Phillips (16) ob-

1779

CAMILLERI AND NERI

O

Jt "]so mm Hg /

J:

A b d o m i n a l : rain -~ d i s c o m f o r t --

Fig 2. Discrete clustered conditions in the jejunum associated with symptoms in a patient with irritable bowel syndrome. This is an example of one type of motor alteration described in IBS patients. (Reproduced with permission from reference 16.)

served that MMCs were more frequent in patients with IBS and diarrhea than those with constipation or healthy controls. Such simple categorization according to bowel habit is not applied in some of the other studies of IBS patients in whom frequency of MMC was one of the major variables assessed. The concomitant occurrence of abdominal pain with minute or discrete clustered contractions (DCC) (Figure 2) or prolonged propagated contractions (PPC) in the ileocolonic segment suggested these motor patterns may have been the cause of the symptoms experienced. The former pattern had already been recorded in IBS patients by Horowitz and Farrar (30), but it also occurs during fasting in asymptomatic healthy controls and in patients with mechanical (31, 32) or functional obstruction [ileal pouch-anal anastomosis (33)]. PPC is a manometric pattern that occurs infrequently in healthy individuals and may result from coloileal reflux of short- chain fatty acids (34, 35). The minute rhythm or discrete clustered activity during phase II of the MMC was also observed in ambulant IBS patients studied with a novel small bowel motility recording device (36). Since these small bowel motor patterns are not specific for IBS patients, it is their increased frequency or perception that is considered important.

The transit of radiolabeled bran through the distal small bowel was reported to be delayed in IBS patients compared to age- and sex-matched healthy controls (37). In the latter study, there was lack of uniformity in the position of the radiolabel in the small bowel at the start of the evaluation, which was arbitrarily started 3 hr after its ingestion. Hence, no clear conclusion can be drawn on small bowel transit from these studies.

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Colon

There is no definite quantitative contractile or myoelectric activity of the colon that clearly differ- entiates IBS patients from healthy controls (1-6): reports on resting colonic motility in IBS range from reduced (2) to normal (7) to increased (1, 2, 38)!

In early studies by Chaudhary and Truelove (38), resting colonic motility index was increased in symptomatic patients with IBS and constipation; in contrast, during the asymptomatic period, individuals with IBS and constipation and those with IBS and diarrhea had normal colonic motility.

In more recent studies of the colonic motility recordings of constipated IBS patients, no differences were reported when compared to normals (5). Sigmoid hypomotility in fasting IBS patients (39) is consistent with the hypothesis that there is an increased sympathetic tone, and features of increased autonomic arousal have been reported in such patients (40). As stated at the beginning of this article, the difficulty in the appraisal of motility in IBS patients is complicated by the relatively high frequency of unreported symptoms consistent with the irritable bowel syndrome in the general population (14, 15) from which individuals are selected as a healthy control group in these studies.

Snape and coworkers (3, 8) have described a three cycle per minute myoelectric oscillation during 40% of the study duration in fasting IBS patients, but this was not associated with any differ- ence in s imultaneously recorded contractile activity. In another study, three cycle per minute slow wave activity was present during both asymp-



tomatic phases and during relapses of IBS symptoms (41). Others (7) observed "fast contractions," which have a duration of less than 15 sec, in IBS patients with diarrhea. These heterogeneous patterns of myoelectric and contractile activity require further evaluation.

In preliminary studies (42) using simultaneous colonic manometry and transit of liquid radiolabel instilled into the splenic plexure of IBS patients, it was shown that patients with predominant diarrhea developed rapid transit during giant migrating contractions that are similar to the propulsive ileal prolonged propagated contractions. In contrast, IBS patients with constipation failed to develop such colonic pressure activity; this was associated with prolonged stasis or retrograde movement of colonic contents.

EFFECTS OF STRESS ON GUT MOTILITY IN HEALTH AND IBS

As in the section describing motility disturbances in patients with functional gastrointestinal disease in the absence of stress, we have categorized effects of stress on gut motility in different anatomic regions.

Esophagus

The relationship between anxiety and globus hys- tericus is an accepted clinical entity. In healthy volunteers, acute emotional stress results in a mean increase of 12mmHg in the upper esophageal sphincter tone, when compared with a nonstressed period. Simultaneous alterations in skin conduc- tance suggest autonomic activation, but the mechanism for this presumed interaction between the brain and striated esophageal muscle interaction remains to be elucidated (43). Although psychological profiles of patients with globus sensation iden- tified more neuroticism, anxiety, and depression than in healthy controls, the responses to acute mental stress were comparable in the two groups, suggesting that mechanisms other than altered perception of stress account for symptoms of globus sensation (24).

In response to experimental psychologic stress, Richter et al reported a higher amplitude of distal esophageal contractions in patients with nutcracker esophagus and patients with noncardiac chest pain, but normal baseline esophageal motility (44). There were no qualitative abnormalities in esophageal motility (such as spontaneous repetitive or triphasic


contractions) in response to stress. There is evidence for an abnormal sensory perception in patients with esophageal chest pain (45).

Stomach

Healthy Subjects. The effect of painful stress induced by immersion of the hand into ice-cold water (46) resulted in a significant reduction in the gastric emptying of a liquid meal, which presumably reflects the effect of stress on the motor function of the gastric fundus. This observation contrasts with the lack of any significant effect of the dichotomous listening stress on the emptying of 99mTc-radiolabeled mashed potatoes (47). In the latter study, familiarity with some aspects of the stressful stimulus, adaptation, and the lack of randomization may have influenced the response to the stressful stimulus by the medical students who performed this investigation on each other.

In another study (48), cold pain also inhibited antral motility and increased plasma levels of beta-endorphin and norepinephrine. The administration of naloxone and nonspecific adrenergic blockers inhibited the effect of cold pain but had no effect on postprandial antral motility in the absence of stress (49). Transcutaneous electrical nerve stimulation applied to the hand or abdominal dermatomes similarly reduced postprandial antral motility, while simultaneously elevating the circulating levels of beta-endorphin (50). How- ever, a neurally mediated somatovisceral reflex could also be responsible for the observations, particularly since beta-endorphin levels required to induce similar effects are several orders of magnitude higher (51) than those observed during painful stress.

Functional Dyspepsia and IBS Patients. Transcu- taneous electrical nerve stimulation applied in ran- domized order (sham or active) induced no change in antral motility in those who had baseline antral hypomotility during the sham study (Figure 3). In contrast, somatic stress induced a reduction in the antral motility index of those with normal distal gastric motor function. This reduction in antral motility was of similar magnitude to that of healthy controls. More recently, others have shown that cold stress induces a profound gastric (fundal) re- laxation of similar magnitude in health and functional dyspepsia (52). In contrast, isobaric distension with a flaccid balloon was perceived as painful at significantly lower volumes in dyspeptic patients (53).

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i 0.550

.r 0.500

E 0.450 ~

0.350 " / 0.300

L,.-. HEALTH -._1 I ~ DYSPEPSIA ~ 1 Normal post- Poslcibal cibal motility hypomotility

Fig 3. Comparison of effect of sham and active somatic painful (transcutaneous electrical nerve stimulation, TENS) stress on antral motility in healthy controls and functional dyspepsia with normal or reduced postcibal antral motility. Note that healthy controls and dyspeptics with normal baseline antral motility have similar reductions in antral motility in response to stress. (Re- produced with permission from reference 26.)

Small Bowel

Healthy Subjects. In healthy volunteers, labyrinthine stimulation induced by cold water irrigation of the tympanic membrane (54) resulted in decreased gastric emptying as well as the occurrence of a phase III-like propagated phasic pressure activity in the postprandial period. These were associated with an increase in plasma beta-endorphin and catechol- amines (48). While stimulation of this vestibular brain-stem reflex induced phase IIl-like activity, psychological stress with the dichotomous listening method (presumably relaying at the cerebral corti- cal level) had either inhibitory effects on small bowel motility, reducing fasting MMCs (55), or a stimulatory effect, reducing small bowel transit time (47). These differences in the effects of stressful stimuli on gut motility may result from the different levels of relay in the central nervous system. How- ever, the short duration (4 hr) of the fasting study, adaptation to the stressful stimulus in four of the 1 l subjects, and lack of randomization in the order of the stress and nonstress periods (55) may also have influenced the frequency of MMCs.

A more prolonged 36- to 48-hr study (56) utilizing a variety of cortically-relaying stressful stimuli showed a reduction in the frequency of MMCs during daytime. At nighttime, there was no differ- ence in the number of MMCs observed between stressed (sleep interruption) and nonstressed periods. These differences are not easy to explain. The nature of the stress may have been responsible for

CAMILLERI AND NERI

these differences, but certainly not the degree of stress, since the distress experienced was far more unpleasant than daytime stress on the basis of visual analog scores and alterations in autonomic stimulation as shown by changes in skin conduc- tance. Reversal of the inhibitory effects of daytime stress on the MMC by metoclopramide (56) might be due to central effects of metoclopramide, as suggested by the authors. An equally tenable hypothesis is that the drug resulted in the accelerated emptying of food from the upper gastrointestinal tract and the more rapid reestablishment of fasting conditions, leading to return of MMCs at the proximal levels monitored by the radiotelemetric capsules.

IBS Patients. In a study using radiotelemetric capsules in normals (healthy controls), inflammatory bowel disease patients (diseased controls), and IBS patients (11), three different types of psychological stress resulted in a reduction in the frequency of MMCs in the IBS group as well as in the two control groups studied (Figure 4). One interpretation of this data is that the reduction in MMC frequency with stress is not specific to the IBS group. An intriguing finding in the study by Kumar and Wingate (11), is the presence of "abnormal irregular contractions" during stress that coincided with symptoms in patients with IBS. Kellow and Phillips (16) also reported a prolongation of phase II interdigestive motility in IBS patients with constipation or diarrhea in the absence of stress. Pro- longed ambulatory recordings may demonstrate whether this irregular activity occurs spontaneously or only in response to stress in such patients.

Colon

Standardized acute stressful conditions resulted in increased colonic pressure activity in both IBS patients (13) and normals (57). Adaptation to stress was noted since repeating the same experimental conditions did not result in any increase in colonic motility in healthy volunteers (57). While physical stress increased the gastrocolonic response to a meal, mental stress reduces the sigmoid colon pressure response, suggesting that the modality of the stress may be important in determining the nature of the colonic response (58). Administration of an oral benzodiazepine to the IBS patients prevented the effect of stress on colonic motility, although an adaptive response similar to that observed in healthy controls cannot be excluded in these patients (57). The state of awareness of the individual

1782 Digestive Diseases and Sciences, Vol. 34, No. 11 (November 1989)


i i i i i II I I 5

! I I I , a . ! I

! ! ! !

'i ' 'I ' I I I

I I I 9 ! 91 I o I I

C O N T R O L ST'RESS C O N T R O L STREW C O N T R O L ST1RES,8

Fig 4. Comparison of the effect of psychologic stress on frequency of migrating motor complexes in healthy controls (left), diseased controls (inflammatory bowel disease, middle plot), and patients with irritable bowel syndrome (right). A similar response to this stressful stimulus is observed in the three groups. (Reproduced with permission from reference 11.)

during the study may influence the colonic myoelectric recordings: vigilant subjects had a similar electrical activity to that seen during cold pain, while activity recorded during rest was significantly lower (59).

CONCLUSION AND A LOOK TO THE FUTURE

There are quantitative differences in pressure activity recorded in the gut of patients with IBS such as the subsets of patients with prominent gastrocolonic reflex or those with functional dyspepsia and antral hypomotility, and the increased irregular contractile activity during fasting phase II. Qualitative analysis of motility recordings from such patients fails to show any abnormal motility patterns. The concurrence of abdominal cramps with discrete clustered contractions and ileal prolonged propagated contractions, as well as the perception of balloon distension in the rectum, colon, ileum, gastric fundus and esophagus at lower volumes suggest that other paradigms should be considered in the IBS, apart from the classical association of stress with alteration in motor function. In fact, the gastric, small bowel, and colonic responses to psychological or somatic stress are no different in functional gastrointestinal disorder patients from those of appropriate healthy or disease control groups. While the application of stressful stimuli in healthy volunteers provides a means for assessing the potential interaction between the psyche and gut motor function, it remains debatable whether these studies are a realistic model for IBS. Pro-

longed assessment of motility during everyday life may provide more conclusive evidence for daily stress in altering motility in the IBS patients.

Future studies in patients with functional gastrointestinal disorders should address other paradigms including: first, assessment for an associated "organic" etiology, such as the evidence of an autonomic neuropathy (60, 61); second, studies on the afferent input and central processing of stimuli arising in the gut in order to understand the cause of differences in perception of intraluminal stimuli or alterations in gut motility; third, since symptoms of psychologic distress appear unre- lated to IBS but do influence which patients con- sult a doctor (62), it is necessary to evaluate motility in IBS subjects who have not sought medical attention for their illness and who score normally on psychologic testing.

It is quite clear that the mechanisms underlying symptoms in IBS patients are heterogeneous; cor- rection of these different pathophysiologic pro- cesses consequently requires different and specific strategies, such as the use of prokinetic medications in those with impaired gastric emptying or colonic transit, in whom antispasmodics, calcium-channel blockers and psychotropic agents might be delete- rious. The generally disappointing results with anx- iolytic and psychotropic agents also suggest that alternative strategies need to be developed to alter perception of luminal stimuli in those patients in whom no quantitative disorder of gut motility is identifiable.

Digestive Diseases and Sciences, Vol. 34, No. 11 (November 1989) 1 7 8 3


ACKNOWLEDGMENTS

We wish to thank Dr. S.F. Phillips for stimulating discussions and advice, and Mrs. Linda Bakken, Mrs. Cindy Stanislav, and Ms. Robin Williams for typing and preparing this manuscript.

APPENDIX

Cold pain. The nondominant hand of the subject is repeatedly immersed for 1-min intervals into water at 4~ and removed for 15 sec between immersions. The cycles are usually repeated for a period of 10-20 min.

Labyrinthine Stimulation. Instillation of water at 4~ into the external auditory meatus of one ear at a rate of 1 ml/sec until a definite sensation of rotation is experienced.

Dichotic Listening. Two texts are delivered simultaneously, one to each ear, and at random intervals, a buzzer or bell is sounded, and the subject is expected to pay attention to one of the texts (according to a prespecified code, eg, buzzer- - lef t ear) and to write every sixth word or to answer written questions pertaining to the text.

Delayed Auditory Feedback. A tape recorder with a third head is used to impose a delay of up to 0.17 sec on an audio signal that is recorded as the subject reads from a text. This delayed signal is fed back to the subject through head phones and results in incor- rect perception of speech. This inability to monitor sound prevents fluent speech and causes distress.

Stroop Test. Subjects are exposed in fast se- quence to two overlapping but different stimuli and are expected to separate and appreciate the stimuli. Commonly, the test involves reading in fast se- quence 50 cards on which the names of colors are written in another color.

Ball Sorting Test. The subject is required to fit small balls (with very slight differences in diameter in the range between 1/8 and 1/4 inch) into holes of the same diameters within a certain time period.

Transcutaneous Electrical Nerve Stimulation. This provides a sustained painful stimulus to the skin by means of an electrical current with standardized pulse width (110 txsec) and rate (110 pulses/sec). The amplitude of the electrical current is varied between 2 mA and 60 mA to overcome adaptation to pain sensation.

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S T R E S S A N D M O T I L I T Y IN IBS

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49. Stanghellini V, Malagelada J-R, Zinsmeister AR, Go VLW, Kao PC: Effect of opiate and adrenergic blockers on the gut motor response to centrally acting stimuli. Gastroenterology 87:1104-1113, 1984

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52. Mearin F, Cucala M, Azpiroz F, Malagelada JR: Origin of gastric symptoms in functional dyspepsia. Gastroenterology 96:A337, 1989

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Digestive Diseases and Sciences, Vol. 34, No. 11 (November 1989) 1785


57. Narducci F, Snape WJ, Battle WM, London RL, Cohen S: Increased colonic motility during exposure to a stressful situation. Dig Dis Sci 30:40-44, 1985

58. Erckenbrecht JF, Butsch BH, Enck P: Physical stress increases, mental stress decreases the gastrocolonic response to eating. Gastroenterology 96:A141, 1989

59. Schang J-C, Devroede G, Hebert M, Hemond M, Pilote M, Devroede L: Effects of rest, stress and food on myoelectric spiking activity of left and sigmoid colon in humans. Dig Dis Sci 33:614-618, 1988

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61. Camilleri M, Fea!ey RD: Idiopathic autonomic denervation (AD): An unrecognized cause of dysmotility in patients with apparently functional bowel disorders. Gastroenterology 95:858, 1988 (abstract)

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motility disorders and stress

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