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Pain Sensitivity in Patients with Irritable Bowel Syndrome

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Pain Sensitivity in Patients with Irritable Bowel Syndrome
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Roth, Nathan T.
Fillingim, Roger
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Pain Sensitivity in Patients with Irritable Bowel Syndrome

Nathan T. Roth, BS, G. Nicholas Verne, MD, Roger B. Fillingim, PhD


ABSTRACT


Visceral hypersensitivity has become a clinical marker for Irritable Bowel Syndrome (IBS), a common

gastrointestinal disorder in the United States. This study was designed to determine whether

hypersensitivity displayed by patients with IBS extends to somatic tissues. A total of 16 IBS patients (15

women and 1 man) and 16 age/sex/race matched controls participated in the study. Pain

procedures included thermal pain and ischemic pain tests. Thermal testing evaluated pain threshold,

pain tolerance, and intensity ratings of temporal summation. Ischemic pain testing included measures

of pain threshold and tolerance, and ratings of pain unpleasantness and pain intensity. Although

no statistically significant group differences were found, certain trends arose that suggest the lack

of significance may be a result of the small sample size. IBS patients were slightly less sensitive

to thermal temporal summation procedure displaying lower pain intensity ratings at both 49 and

520C. However, IBS patients showed somewhat lower values for pain threshold and pain tolerance

in response to ischemic pain. The small sample size in this study may have prevented

statistical significance from being achieved given the trends obtained in the results. Nevertheless,

there is limited support for the hypothesis that differences in somatic pain perception between

IBS patients and controls are dependent on the type of stimulation, with IBS patients displaying

a greater pain sensitivity for deep, tonic pain (ischemic pain) than for brief, superficial (thermal pain).



INTRODUCTION


Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is estimated to affect 20%

of the United States population (Verne & Cerda, 1997). IBS is one of the most frequent

gastrointestinal disorders seen by physicians, comprising 50% of referrals to gastroenterologists and

as many as 3.5 million visits to physicians each year in the United States (Sandier, 1990).

Symptoms include chronic abdominal pain and altered bowel function (diarrhea and/or constipation)

as well as feelings of urgency and bloating. Patients with IBS may also experience extra-

intestinal symptoms that include migraine headaches, dyspareunia, heartburn, muscle pain, and

back pain (Mayer & Gebhart, 1994; Mayer & Raybould, 1990). Currently, treatments for IBS are

limited due to limited understanding of the mechanisms of the disorder, varying symptoms, and the

lack of unique target receptors for pharmacotherapy (De Ponti & Malagelada, 1998).







Initially, IBS was considered to be a motility disorder in which discrete cluster contractions in

the jejunum were more frequently observed in patients with IBS ("American

Gastroenterological Association"). However, research has failed to show this abnormal motility

pattern consistently in IBS patients. Recent studies have shown that IBS patients display

visceral hypersensitivity suggesting that IBS may be a disorder of altered perception (Verne &

Cerda, 1997). This has been demonstrated with balloon distention studies in which IBS patients

are aware of rectal or rectosigmoid distension and pain at significantly lower balloon pressures

and volumes compared to control subjects (Mayer & Gebhart, 1994; Mayer and Raybould, 1990).

Visceral hypersensitivity has now become a clinical marker for IBS; however the

pathophysiological mechanisms of pain and hypersensitivity in IBS are not well understood. The

first studies to address possible mechanisms of IBS suggested that the hyperalgesia in IBS is limited

to the gut (Accarino, Azpiroz, & Malagelada, 1995; Chang, Mayer, Johnson, Fitzgerald, & Naliboff,

2000; Cook, Van Eeden, & Collins, 1987; Whitehead, Holtkotter, Enck, Hoelzl, Holmes, Anthony,

Shabsin, & Schuster, 1990; Zighelboim, Talley, Philips, Harmsen, & Zinsmeister, 1995). However,

recent evidence has shown that patients with IBS also experience somatic hypersensitivity

from experimental thermal pain stimuli (Verne, Robinson, & Price, 2001).



This study was designed to further explore the possibility of somatic pain hypersensitivity and

altered perception in patients with IBS by comparing responses of both IBS patients and controls to

two clinically relevant somatic pain stimuli (thermal pain, ischemic pain). It was hypothesized that

IBS patients will display hypersensitivity to these nociceptive stimuli compared to controls with

greater sensitivity for deep, tonic stimuli (ischemic pain) than for superficial, brief stimuli (thermal

pain). The belief is that better understanding of the hypersensitivity in IBS patients could lead to

the development of improved treatments for Irritable Bowel Syndrome.



METHODS



A total of 16 IBS patients (15 women and 1 man) and 16 age, sex, and race matched controls

were tested. Both groups were 75% Caucasian. Hispanics, African Americans, Asians and an

"other" category each composed 6.25% of the sample. The average age for the IBS patient group

was 26.8 years. Average age for controls was 24.4 years. Research subjects were recruited from

area clinics and newspaper advertisements. All IBS subjects were required to meet the Rome II

Criteria for IBS.



Rome II Criteria


At least 12 weeks of abdominal pain that need not be consecutive in the preceding 12 months,

of abdominal discomfort or pain that has 2 of 3 features (51):







. Relieved with defecation


Onset associated with a change in frequency of stool


Onset associated with a change in form (appearance of stool)


Subjects were seated in a comfortable chair in a quiet room during testing. Two experimenters

conducted each session. Each subject underwent two well-validated somatic pain stimuli (thermal

pain, ischemic pain).


Thermal Procedures


Threshold/Tolerance. Contact heat stimuli were delivered using a computer-controlled Medoc

Thermal Sensory Analyzer (TSA-2001, Ramat Yishai, Israel), which is a peltier-element-based

stimulator. Detection of warmth (warmth threshold, hpth), first pain sensation (heat pain threshold)

and pain limit (heat pain tolerance, hpto) were assessed on the ventral forearm using an

ascending method of limits with a 0.5 deg C/sec rate of rise.



Temporal Summation. In this procedure, the same thermal stimulator was positioned on the

ventral forearm. The two intertribal intensities were 38 and 41oC, and the target temperatures were

49 and 520C, respectively. The target temperature was delivered for a 1-second duration, with a

3-second interpulse interval at the intertribal intensity. A total of 10 trials were delivered.

Participants provided intensity ratings of each stimulus using a 0-100 scale, and the average

rating across all 10 trials was computed for each temperature.



Ischemic Pain Procedure


The left arm was exsanguinated by elevating it above ear level for 30 sec, and then the arm was

occluded with a standard blood pressure cuff inflated to 240 mm Hg. Participants performed 20

handgrip exercises of 2-second duration at 4-second intervals at 50% of their maximum grip

strength. Participants continued until the perceived pain became intolerable or for 15-minutes. The

time at which the ischemic stimulus first produced pain (Ischemic Pain Threshold, IPTh) and the time

at which subjects no longer felt able to tolerate the pain (Ischemic Pain Tolerance, IPTo) were recorded.



Data Analysis


Analysis of Variance (ANOVA) was used to determine the statistical significance of group (IBS

vs. Control) differences in pain responses. Data are presented as means and standard deviations,

unless otherwise indicated.






RESULTS


For this sample size, IBS patients and controls were not found to differ significantly in any of the

pain testing. However, intensity ratings for the thermal pain temporal summation procedure were

found to be lower with marginal significance in IBS patients (p = .056). Table 1 gives intensity ratings

for both groups at 49 and 520C.



Table 1
Group Comparison of intensity ratings for Thermal Pain Temporal Summation
procedures
IBS Patients Controls
Intensity Rating Mean (SE) Mean (SE)
Intensity Rating (49"C) 47.5 (6.5) 66.5 (7.0)
Intensity Rating (52*C) 72.7 (6.4) 84.2 (5.8)


Ischemic threshold and tolerance for both groups is given in Table 2. Although not

statistically significant, both IPTh and IPTo values were lower in IBS patients. Figure 1 clearly

shows skewed distributions of IBS patients and controls for IPTo values.



Table 2
Group Comparison of Ischemic Pain Threshold and Tolerance
IBS Patients Controls
Type Mean (SE) Mean (SE)
Ischemic Pain Threshold (s) 121.9 (18.5) 178.7 (37.5)
Ischemic Pain Tolerance (s) 426.4 (66.2) 580.9 (72.0)






35
30- ~IBS
20 UControls




S-
a25
20
-15
C 10


60 180 300 420 540 660 780 900
Ischemic Pain Tolerance Time (s)



Figure 1. Percentage of IBS patients and controls at different Ischemic Pain Tolerance times.




No differences were found for thermal pain threshold or tolerance. These data are shown in Table 3.



Table 3
Group Comparison of Thermal Pain Threshold and Tolerance
IBS Patients Controls
Type Mean (SE) Mean (SE)
Thermal Pain Threshold (�C) 40.5 (0.9) 40.7 (0.6)





Thermal Pain Tolerance (�C) 45.6 (0.6)


DISCUSSION



Despite failing to find statistically significant differences in pain perception between IBS patients

and controls in this study, the pattern of results suggests that differences in somatic pain

perception between IBS patients and controls may vary across pain modalities. Specifically, the trends

in pain intensity ratings for the thermal temporal summation procedure suggest slightly lower

pain sensitivity among IBS patients, while the ischemic pain tolerance values imply elevated

pain sensitivity in IBS patients. It is believed that the lack of statistical significance may have

resulted from the limited sample size in this study. Therefore, additional research is required with

a larger sample size to determine if differences in pain perception exist for IBS patients compared

to control subjects.



When comparing threshold and tolerance values for both thermal and ischemic pain in both groups, it

is evident that a greater difference arises between the groups for ischemic pain, with IBS

patients displaying lower values for both threshold and tolerance. These results provide limited

support for the hypothesis that enhanced pain responsivity in IBS patients may be most pronounced

for deep, tonic stimuli (ischemic pain) than for superficial, brief stimuli (thermal pain) when compared

to controls. Again, statistical significance was not achieved, and the implications of these findings

will remain unclear without further research.



Since little is known about the pathophysiological mechanisms of pain and hypersensitivity in

Irritable Bowel Syndrome, it will remain difficult to diagnose and treat this prevalent disorder.

If hypersensitivity in IBS patients is found to extend beyond the viscera, it may characterize IBS as

a disorder of central pain processing and ultimately lead to novel research, diagnosis, and

treatment methods. Indeed, IBS is still not well-defined, and it is even believed that it may be

composed of different subsets, based on stool consistency and frequency, that collectively comprise

all IBS patients. It is possible that pain perceptions differ between these subsets as well,

and characterization of these differences would also provide valuable information for diagnosis

and treatment methods. There remains much to discover about the mechanisms of pain in IBS patients

as well as the optimal treatment of the disorder.






REFERENCES



1. Accarino, A., Azpiroz, F., & Malagelada, J.R. (1995). Selective dysfunction of mechanosensitive

intestinal afferents in the irritable bowel syndrome. Gastroenterology, 10, 636-643.


45.7 (0.6)




2. American Gastroenterological Association (1997). Medical position statement: irritable bowel

syndrome. Gastroenterology, 112, 2118-2119.

3. Chang, L., Mayer, E. A., Johnson, T., FitzGerald, L.Z., & Naliboff, B. (2000). Differences in

somatic perception in female patients with irritable bowel syndrome with and without fibromyalgia.

Pain, 84, 297-307.

4. Cook, .J., Van Eeden, A., & Collins, S.M. (1987). Patients with irritable bowel syndrome have greater

pain tolerance than normal subjects. Gastroenterology, 93, 701-708.

5. De Ponti, R., Malagelada, J. R., (1998). Functional gut disorders: From motility to sensitivity disorders.

A review of current and investigational drugs for their management. Pharmacologic Therapeutics, 80,

49-88.

6. Mayer, E. A., Gebhart, G. F., (1994). Basic and clinical aspects of visceral hyperalgesia.

Gastroenterology, 107, 271-293.

7. Mayer, E.A., & Raybould, H.E. (1990). Role of visceral afferent mechanisms in functional bowel

disorders. Gastroenterology, 99, 1688-1704.

8. Sander R. S. (1990). Epidemiology of irritable bowel syndrome in the United States.

Gastroenterology, 99, 409-415.

9. Verne, G. N., & Cerda, J. J. (1997). Streamlining the diagnosis of the irritable colon

syndrome. Postgraduate Medicine, 102, 197-208.

10. Verne, G. N., Robinson, M. E., & Price, D. D. (2001). Hypersensitivity to visceral and cutaneous pain in

the irritable bowel syndrome. Pain, 93, 7-14.

11. Whitehead, W. E., Holtkotter, B., Enck, P., Hoelzl, R., Holmes, K. D., Anthony, J., Shabsin, H.S., &

Schuster, M. M. (1990). Tolerance for rectosigmoid distention in irritable bowel

syndrome. Gastroenterology, 98, 1187-1192.

12. Zighelboim, J., Talley, N. J., Phillips, S. F., Harmsen, W. S., & Zinsmeister, A. R. (1995).

Visceral perception in irritable bowel syndrome. Digestive Diseases and Sciences, 40, 819-827.





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PAGE 1

Journal of Undergraduate Research Volume 6, Issue 7 May/June 2005 Pain Sensitivity in Patients with Irritable Bowel SyndromeNathan T. Roth, BS, G. Nicholas Verne, MD, Roger B. Fillingim, PhD ABSTRACTVisceral hypersensitivity has become a clinical marker for Irritable Bowel Syndrome (IBS), a common gastrointestinal disorder in the United States. This study was designed to determine whether hypersensitivity displayed by patients with IBS extends to somatic tissues. A total of 16 IBS patients (15 women and 1 man) and 16 age/sex/race matched controls participated in the study. Pain procedures included thermal pain and ischemic pain tests. Thermal testing evaluated pain threshold, pain tolerance, and intensity ratings of temporal summation. Ischemic pain testing included measures of pain threshold and tolerance, and ratings of pain unpleasantness and pain intensity. Although no statistically significant group differences were found, certain trends arose that suggest the lack of significance may be a result of the small sample size. IBS patients were slightly less sensitive to thermal temporal summation procedure displaying lower pain intensity ratings at both 49 and 520C. However, IBS patients showed somewhat lower values for pain threshold and pain tolerance in response to ischemic pain. The small sample size in this study may have prevented statistical significance from being achieved given the trends obtained in the results. Nevertheless, there is limited support for the hypothesis that differences in somatic pain perception between IBS patients and controls are dependent on the type of stimulation, with IBS patients displaying a greater pain sensitivity for deep, tonic pain (ischemic pain) than for brief, superficial (thermal pain).INTRODUCTIONIrritable bowel syndrome (IBS) is a common gastrointestinal disorder that is estimated to affect 20% of the United States population (Verne & Cerda, 1997). IBS is one of the most frequent gastrointestinal disorders seen by physicians, comprising 50% of referrals to gastroenterologists and as many as 3.5 million visits to physicians each year in the United States (Sandler, 1990). Symptoms include chronic abdominal pain and altered bowel function (diarrhea and/or constipation) as well as feelings of urgency and bloating. Patients with IBS may also experience extraintestinal symptoms that include migraine headaches, dyspareunia, heartburn, muscle pain, and back pain (Mayer & Gebhart, 1994; Mayer & Raybould, 1990). Currently, treatments for IBS are limited due to limited understanding of the mechanisms of the disorder, varying symptoms, and the lack of unique target receptors for pharmacotherapy (De Ponti & Malagelada, 1998).

PAGE 2

Initially, IBS was considered to be a motility disorder in which discrete cluster contractions in the jejunum were more frequently observed in patients with IBS (American Gastroenterological Association). However, research has failed to show this abnormal motility pattern consistently in IBS patients. Recent studies have shown that IBS patients display visceral hypersensitivity suggesting that IBS may be a disorder of altered perception (Verne & Cerda, 1997). This has been demonstrated with balloon distention studies in which IBS patients are aware of rectal or rectosigmoid distension and pain at significantly lower balloon pressures and volumes compared to control subjects (Mayer & Gebhart, 1994; Mayer and Raybould, 1990). Visceral hypersensitivity has now become a clinical marker for IBS; however the pathophysiological mechanisms of pain and hypersensitivity in IBS are not well understood. The first studies to address possible mechanisms of IBS suggested that the hyperalgesia in IBS is limited to the gut (Accarino, Azpiroz, & Malagelada, 1995; Chang, Mayer, Johnson, Fitzgerald, & Naliboff, 2000; Cook, Van Eeden, & Collins, 1987; Whitehead, Holtkotter, Enck, Hoelzl, Holmes, Anthony, Shabsin, & Schuster, 1990; Zighelboim, Talley, Philips, Harmsen, & Zinsmeister, 1995). However, recent evidence has shown that patients with IBS also experience somatic hypersensitivity from experimental thermal pain stimuli (Verne, Robinson, & Price, 2001). This study was designed to further explore the possibility of somatic pain hypersensitivity and altered perception in patients with IBS by comparing responses of both IBS patients and controls to two clinically relevant somatic pain stimuli (thermal pain, ischemic pain). It was hypothesized that IBS patients will display hypersensitivity to these nociceptive stimuli compared to controls with greater sensitivity for deep, tonic stimuli (ischemic pain) than for superficial, brief stimuli (thermal pain). The belief is that better understanding of the hypersensitivity in IBS patients could lead to the development of improved treatments for Irritable Bowel Syndrome. METHODSA total of 16 IBS patients (15 women and 1 man) and 16 age, sex, and race matched controls were tested. Both groups were 75% Caucasian. Hispanics, African Americans, Asians and an other category each composed 6.25% of the sample. The average age for the IBS patient group was 26.8 years. Average age for controls was 24.4 years. Research subjects were recruited from area clinics and newspaper advertisements. All IBS subjects were required to meet the Rome II Criteria for IBS. Rome II Criteria At least 12 weeks of abdominal pain that need not be consecutive in the preceding 12 months, of abdominal discomfort or pain that has 2 of 3 features (51):

PAGE 3

Relieved with defecation Onset associated with a change in frequency of stool Onset associated with a change in form (appearance of stool) Subjects were seated in a comfortable chair in a quiet room during testing. Two experimenters conducted each session. Each subject underwent two well-validated somatic pain stimuli (thermal pain, ischemic pain). Thermal Procedures Threshold/Tolerance. Contact heat stimuli were delivered using a computer-controlled Medoc Thermal Sensory Analyzer (TSA-2001, Ramat Yishai, Israel), which is a peltier-element-based stimulator. Detection of warmth (warmth threshold, hpth), first pain sensation (heat pain threshold) and pain limit (heat pain tolerance, hpto) were assessed on the ventral forearm using an ascending method of limits with a 0.5 deg C/sec rate of rise. Temporal Summation. In this procedure, the same thermal stimulator was positioned on the ventral forearm. The two intertribal intensities were 38 and 41oC, and the target temperatures were 49 and 520C, respectively. The target temperature was delivered for a 1-second duration, with a 3-second interpulse interval at the intertribal intensity. A total of 10 trials were delivered. Participants provided intensity ratings of each stimulus using a 0-100 scale, and the average rating across all 10 trials was computed for each temperature. Ischemic Pain Procedure The left arm was exsanguinated by elevating it above ear level for 30 sec, and then the arm was occluded with a standard blood pressure cuff inflated to 240 mm Hg. Participants performed 20 handgrip exercises of 2-second duration at 4-second intervals at 50% of their maximum grip strength. Participants continued until the perceived pain became intolerable or for 15-minutes. The time at which the ischemic stimulus first produced pain (Ischemic Pain Threshold, IPTh) and the time at which subjects no longer felt able to tolerate the pain (Ischemic Pain Tolerance, IPTo) were recorded. Data Analysis Analysis of Variance (ANOVA) was used to determine the statistical significance of group (IBS vs. Control) differences in pain responses. Data are presented as means and standard deviations, unless otherwise indicated.

PAGE 4

RESULTSFor this sample size, IBS patients and controls were not found to differ significantly in any of the pain testing. However, intensity ratings for the thermal pain temporal summation procedure were found to be lower with marginal significance in IBS patients (p = .056). Table 1 gives intensity ratings for both groups at 49 and 520C. Table 1 Group Comparison of intensity ratings for Thermal Pain Temporal Summation procedures Intensity Rating IBS Patients Mean (SE) Controls Mean (SE) Intensity Rating (49C) 47.5 (6.5) 66.5 (7.0) Intensity Rating (52C) 72.7 (6.4) 84.2 (5.8) Ischemic threshold and tolerance for both groups is given in Table 2. Although not statistically significant, both IPTh and IPTo values were lower in IBS patients. Figure 1 clearly shows skewed distributions of IBS patients and controls for IPTo values. Table 2 Group Comparison of Ischemic Pain Threshold and Tolerance Type IBS Patients Mean (SE) Controls Mean (SE) Ischemic Pain Threshold (s) 121.9 (18.5) 178.7 (37.5) Ischemic Pain Tolerance (s) 426.4 (66.2) 580.9 (72.0) Figure 1. Percentage of IBS patients and controls at different Ischemic Pain Tolerance times. No differences were found for thermal pain threshold or tolerance. These data are shown in Table 3. Table 3 Group Comparison of Thermal Pain Threshold and Tolerance Type IBS Patients Mean (SE) Controls Mean (SE) Thermal Pain Threshold (C) 40.5 (0.9) 40.7 (0.6)

PAGE 5

Thermal Pain Tolerance (C) 45.6 (0.6) 45.7 (0.6)DISCUSSIONDespite failing to find statistically significant differences in pain perception between IBS patients and controls in this study, the pattern of results suggests that differences in somatic pain perception between IBS patients and controls may vary across pain modalities. Specifically, the trends in pain intensity ratings for the thermal temporal summation procedure suggest slightly lower pain sensitivity among IBS patients, while the ischemic pain tolerance values imply elevated pain sensitivity in IBS patients. It is believed that the lack of statistical significance may have resulted from the limited sample size in this study. Therefore, additional research is required with a larger sample size to determine if differences in pain perception exist for IBS patients compared to control subjects. When comparing threshold and tolerance values for both thermal and ischemic pain in both groups, it is evident that a greater difference arises between the groups for ischemic pain, with IBS patients displaying lower values for both threshold and tolerance. These results provide limited support for the hypothesis that enhanced pain responsivity in IBS patients may be most pronounced for deep, tonic stimuli (ischemic pain) than for superficial, brief stimuli (thermal pain) when compared to controls. Again, statistical significance was not achieved, and the implications of these findings will remain unclear without further research. Since little is known about the pathophysiological mechanisms of pain and hypersensitivity in Irritable Bowel Syndrome, it will remain difficult to diagnose and treat this prevalent disorder. If hypersensitivity in IBS patients is found to extend beyond the viscera, it may characterize IBS as a disorder of central pain processing and ultimately lead to novel research, diagnosis, and treatment methods. Indeed, IBS is still not well-defined, and it is even believed that it may be composed of different subsets, based on stool consistency and frequency, that collectively comprise all IBS patients. It is possible that pain perceptions differ between these subsets as well, and characterization of these differences would also provide valuable information for diagnosis and treatment methods. There remains much to discover about the mechanisms of pain in IBS patients as well as the optimal treatment of the disorder. REFERENCES1. Accarino, A., Azpiroz, F., & Malagelada, J.R. (1995). Selective dysfunction of mechanosensitive intestinal afferents in the irritable bowel syndrome. Gastroenterology, 10, 636-643.

PAGE 6

2. American Gastroenterological Association (1997). Medical position statement: irritable bowel syndrome. Gastroenterology, 112, 2118-2119. 3. Chang, L., Mayer, E. A., Johnson, T., FitzGerald, L.Z., & Naliboff, B. (2000). Differences in somatic perception in female patients with irritable bowel syndrome with and without fibromyalgia. Pain, 84, 297-307. 4. Cook, I.J., Van Eeden, A., & Collins, S.M. (1987). Patients with irritable bowel syndrome have greater pain tolerance than normal subjects. Gastroenterology, 93, 701-708. 5. De Ponti, R., Malagelada, J. R., (1998). Functional gut disorders: From motility to sensitivity disorders. A review of current and investigational drugs for their management. Pharmacologic Therapeutics, 80, 49-88. 6. Mayer, E. A., Gebhart, G. F., (1994). Basic and clinical aspects of visceral hyperalgesia. Gastroenterology, 107, 271-293. 7. Mayer, E.A., & Raybould, H.E. (1990). Role of visceral afferent mechanisms in functional bowel disorders. Gastroenterology, 99, 1688-1704. 8. Sandler R. S. (1990). Epidemiology of irritable bowel syndrome in the United States. Gastroenterology, 99, 409-415. 9. Verne, G. N., & Cerda, J. J. (1997). Streamlining the diagnosis of the irritable colon syndrome. Postgraduate Medicine, 102, 197-208. 10. Verne, G. N., Robinson, M. E., & Price, D. D. (2001). Hypersensitivity to visceral and cutaneous pain in the irritable bowel syndrome. Pain, 93, 7-14. 11. Whitehead, W. E., Holtkotter, B., Enck, P., Hoelzl, R., Holmes, K. D., Anthony, J., Shabsin, H.S., & Schuster, M. M. (1990). Tolerance for rectosigmoid distention in irritable bowel syndrome. Gastroenterology, 98, 1187-1192. 12. Zighelboim, J., Talley, N. J., Phillips, S. F., Harmsen, W. S., & Zinsmeister, A. R. (1995). Visceral perception in irritable bowel syndrome. Digestive Diseases and Sciences, 40, 819-827. --top-Back to the Journal of Undergraduate Research College of Liberal Arts and Sciences | University Scholars Program | University of Florida | University of Florida, Gainesville, FL 32611; (352) 846-2032.