Good Study, Bad Practice: Placebo for IBS and Functional Abdominal Pain

Have a great day (Mt Yonah, Cleveland GA)

S Nurko et al. JAMA Pediatr. 2022;176(4):349-356. doi:10.1001/jamapediatrics.2021.5750. Adolescents With Functional Abdominal Pain or Irritable Bowel Syndrome

Design: Patients completed 1 week of observation prior to randomization to 1 of 2 counterbalanced groups: OLP for 3 weeks followed by a 3-week control period or control period for 3 weeks followed by OLP for 3 weeks. During the OLP period, participants took 1.5 mL of an inert liquid placebo twice a day.

Key findings:

  • The mean (SD) pain scores were significantly lower during open label placebo (OLP) treatment compared with the control period (39.9 [18.9] vs 45.0 [14.7]; difference, 5.2; 95% CI, 0.2-10.1; P = .03)
  • Patients took nearly twice as many hyoscyamine pills during the control period compared with during the OLP period (mean [SD] number, 3.8 [5.1] pills vs 2.0 [3.0] pills; difference, 1.8 pills; 95% CI, 0.5-3.1 pills)

My take: It is a mistake to consider placebo as a treatment for functional abdominal pain. In many children, pain fluctuates and may improve with reassurance, distraction, healthier diets, and physical activity. However, we also need more effective therapies including pain psychology, dietary approaches and medications. The idea that placebo helps is misleading and undermines the fact that patients with functional disorders need effective treatment.

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Auricular Stimulation Associated with Less Pain, Less Disability, and Better Sleep

N Santucci et al. Neurogastroenterology & Motility. 2022;00:e14358. Effect of percutaneous electrical nerve field stimulation on mechanosensitivity, sleep, and psychological comorbidities in adolescents with functional abdominal pain disorders

This study evaluated the effects of IB-stim® (Innovative Health Solutions, Versailles, IN, USA) in 20 patients (11-19 years old) with functional pain. This external auricular device with a battery powered generator that creates percutaneous electrical nerve field stimulation (PENFS), targeting cranial nerves V, VII, IX, and X. This device which has been associated with improvement in functional abdominal pain previously was evaluated for its effects on resting and evoked pain and nausea, sleep and psychological functioning, and long-term outcomes.

Key Findings:

  • During pain evoked by Water Load Symptom Provocation Task (WL-SPT), visual analog scale (VAS) pain intensity and nausea were lower following PENFS compared with baseline (p = 0.004 and p = 0.02, respectively)
  • After PENFS, resting VAS pain unpleasantness (p = 0.03), abdominal pain (p < 0.0001), pain catastrophizing (p = 0.0004), somatic complaints (0.01), functional disability (p = 0.04), and anxiety (p = 0.02) exhibited significant improvements, and some were sustained long-term.
  • Self-reported sleep improved after PENFS (p’s < 0.05) as well as actigraphy-derived sleep onset latency (p = 0.03). The authors note that, paradoxically, patients receiving neuromodulators had more trouble with sleep at baseline. “It is hard to tease out if these differences are due to the medications themselves or if the patients on these medications have more severe symptoms that may have a bigger impact on their life”
  • In assessing predictors of response to PENFS therapy, those with higher pain catastrophizing and somatization had lesser reduction in VAS pain scores, while those with high anxiety had lesser improvements in functioning.
  • Study limitations: small sample size and lack of control/sham group

In this limited study, PENFS was associated with improvements in pain intensity and nausea through visual analog scales and validated questionnaires. Disability, pain catastrophizing, somatization, and anxiety reduced after four weeks of PENFS and effects were sustained at 6–12 months post-treatment.

My take: Auricular stimulation if feasible (in terms of cost) is a good alternative to pharmacologic therapy. It would be of interest to study outcomes of patients who received this treatment modality compared with those who were treated by well-qualified pain psychologists.

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Osprey on The Hunley Bridge, Isle of Palms, SC

Functional Abdominal Pain in Children with Celiac Disease

F Cristofori et al. Clin Gastroenterol Hepatol 2021; 19: 2551-2558. Functional Abdominal Pain Disorders and Constipation in Children on Gluten-Free Diet

This prospective cohort (2016-2018, n=417, mean age 13.7 y) examined the frequency of functional disorders (based on questionnaire) in children with celiac disease (CD) who were receiving a strict gluten free diet (GFD) for at least one year.

Key findings:

  • Functional abdominal pain disorders (FAPDs) had a higher prevalence s among patients with CD (11.5%) than controls (6.7%)  (P < .05)
  • Irritable bowel syndrome (IBS) and functional constipation (FC) defined by the Rome IV criteria were more prevalent in patients with CD (7.2% for IBS and 19.9% for FC) than controls (3.2% for IBS and 10.5% for FC) (P < .05 and P < .001, respectively)
  • Younger age (P < .05) and a higher level of anti–transglutaminase IgA at diagnosis (P < .04) were associated with FAPDs (in particular for IBS) irrespective of GFD duration
  • A GFD did help with abdominal pain: After starting a GFD, 80% of children with celiac disease had resolution of stomach pain, whereas 9% started to complain of symptoms after starting a GFD

In the discussion, the authors speculate on the reasons for ongoing pain including inadvertent gluten exposure, intestinal inflammation/visceral hyperalgesia, altered microbiome, and refractory CD.

My take: Persistent stomach pain in CD is a common occurrence, even in those trying to adhere to a strict GFD.

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Chattahoochee River, Atlanta

Course of Functional Abdominal Pain Before and During Pandemic

C Strisciuglio et al. JPGN 2021; 73: 689-694. Overall Impact of Coronavirus Disease 2019 Outbreak in Children With Functional Abdominal Pain Disorders: Results From the First Pandemic Phase

In this multicenter, observational, international study conducted between April and July 2020 at six different referral centers, the authors studied two groups:

  1. Children diagnosed with FAPDs between October 2019 and February 2020 were enrolled and prospectively interviewed at 4 months of follow-up during the first pandemic phase (Quarantine group, n=180, mean age 14 yrs)
  2. A cohort of children diagnosed with FAPDs between October 2018 and February 2019 was used as a Control group, n=176, mean age 13 yrs)

Key findings:

  • At 4 months of follow-up, both groups had a significant reduction of children reporting >5 episodes of abdominal pain per month when compared to baseline. Quarantine group: 63.9% vs 42.2%, P < 0.001; Control group: 83.5% vs 50%, P < 0.001.
  • Overall, 57% of the Quarantine group and 63.5% of the Control group had improvement of all symptoms.

My take: This study shows that the majority of patients with functional abdominal pain have improvement (at least temporarily) and reinforce the benefit of reassurance/conservative approach for many even during the pandemic. It is possible that school closures and additional parental attention mitigated some of the improvement in the Quarantine group.

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Siesta Key, FL

Carlo DiLorenzo: Lessons Learnt Over 30 Years

Recently, Carlo DiLorenzo came to Atlanta as the speaker for the William Meyers Lectureship. He provided a terrific talk and was the perfect speaker for this lectureship which honors Billy.

Some of the key points:

  • When giving a lecture, often ‘a great study is one that supports the speaker’s view’
  • Physicians often have biases against patients with functional disorders as compared to those who have “rightful” suffering (eg. cancer, pancreatitis)
  • Key part of patient-physician relationship is listening (by the physician). Patients report better satisfaction and perceive to be understood better when a physician is sitting (while listening). “The most important technological advance in the practice of medicine was the invention of the chair. For you to sit in. While you take the history” (Mark Reid, MD)
  • Diagnoses have side effects
  • Families remember our words for years
  • We are not well-equipped to deliver good news: “This is one of the best colons I have ever seen…Your child has irritable bowel and no other tests are needed.”
  • The most under prescribed treatment: 30 minutes of physical activity everyday
  • 2nd most under prescribed treatment is a good night’s sleep.  Increased symptoms when tired
  • “Psychobezoar,” referring to a fear of discomfort with eating, could be used as an alternative to ARFID
  • Most effective treatment for IBS: cognitive behavioral therapy
  • Distraction is helpful tool for pain but need to teach parents to accept this tool
  • Some of the axioms in the lecture are attributed to Mark Reid, MD

Related blog post: #NASPGHAN19 Postgraduate Course -part 3

Here are some of the slides from this talk:

“Golden Half Hour in Chronic Pain”

A recent editorial (NL Schecter et al. JAMA Pediatr. 2021;175(1):7–8. doi:10.1001/jamapediatrics.2020.1798. Full text: The Golden Half Hour in Chronic Pediatric Pain—Feedback as the First Intervention -thanks to Ben Gold for this reference) notes that with pain we need to take a more holistic approach: ” Commonly, patients with chronic pain are evaluated by multiple clinicians, including pediatricians and specialists, each of whom may have addressed only one of the child’s persistent symptoms (ie, headache, abdominal pain, dizziness, nausea, or fatigue). When each symptom is addressed in isolation, it seldom provides comprehensive relief. Moreover, this process can foster a family’s belief that each symptom represents a distinct illness.”

Key points:

  • Brief feedback discussion following an assessment for pediatric chronic pain may be akin to the “golden hour” in trauma or neonatal care.  During this critical time, there is an opportunity to connect with a family, clarify misconceptions, move toward a shared biopsychosocial understanding of pain, and engage families in a comprehensive plan for recovery.”
  • Tips for mastering the golden hour:
    • Elicit Parent and Child Expectations at the Outset “This facilitates a thorough understanding of a family’s main concerns, reduces anxiety, and improves satisfaction. For example, if a parent reports that they expect their child to undergo additional diagnostic testing, this needs to be appreciated and addressed during the feedback.”
    • Validate Symptoms  “Explicitly stating that you do not believe the child is “faking” or that the problem is merely due to psychological stress is critical”
    • Offer a Positive Diagnosis “Although you are special, your symptoms are not unique or mysterious…. If the focus is on what has been ruled out, there are always additional diagnoses that you, the patient, or the internet can introduce.”
    • Provide Education “it can be helpful to explain that chronic pain is like a fire alarm that keeps ringing although there is no fire. “
    • Emphasize a Multidisciplinary Intervention Plan plan for medical intervention, psychological support, and physical activity
    • Stay Connected “Plan follow-up visits (every 4-6 weeks)”
    • Offer an Optimistic Appraisal  “optimistic appraisals are most effective when a clinician has first validated a child’s pain, provided a positive diagnosis and education, and outlined an evidence-based, multidisciplinary approach to care”

My take: This article offers helpful advice. However, whether there is a “golden hour” of opportunity is not clear. Having better outcomes with early intervention could easily be related, at least in part, to selection bias.

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From Ashish Jha Twitter Feed 2/1/21:

“Implementing psychological therapies for gastrointestinal disorders in pediatrics”

Bonney Reed, Jessica Buzenski & Miranda A.L van TilburgExpert Review of Gastroenterology & Hepatology (2020), DOI: 10.1080/17474124.2020.1806055 Full Text: Implementing psychological therapies for gastrointestinal disorders in pediatrics

This article is a useful and up-to-date review on the role of psychology to treat children with gastrointestinal disorders, particularly targeting functional GI disorders as well as children with inflammatory bowel disease. Also, I want to recognize Bonney and Jessica who have been so helpful for so many of our patients.

Areas covered:

  • Cognitive behavioral therapy (CBT)
  • Gut-directed hypnotherapy
  • Biofeedback-assisted relaxation training
  • E-treatment/telemedicine
  • Emerging therapies: Mindfulness, and Acceptance and Commitment therapy


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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Myth or Fact: Joint Hypermobility is Related to Pediatric Functional Abdominal Pain & Dr. Roy Link

According to a recent study (RJ Shulman et al. J Pediatri 2020; 222: 134-40), the prevalence of joint hypermobility does NOT differ in children with irritable bowel syndrome, functional abdominal pain, or healthy control children.

Methods (to reach this conclusion):

  • Children (median age ~9.5 years) with irritable bowel syndrome (n=109), functional abdominal pain (n=31), and healthy controls (n=69) completed a prospective 2-week pain and stooling diaries.  In addition, children and parents reported on measures of anxiety, depression, and somatization. Children were recruited from both primary care and tertiary care settings
  • Joint hypermobility was determined using Beighton criteria using a goniometer and examined cutoffs at both ≥4 or ≥6).

Key findings:

  • Beighton scores were similar between the groups, as was the proportion with joint hypermobility.  Beighton scores were not related to abdominal pain or stooling characteristics.
  • Beighton score ≥4: IBS 35%, FAP 36%, healthy controls 36%.
  • Beighton score ≥6: IBS 12%, FAP 13%, healthy controls 9%.
  • Children reported depression more frequently in those with Beighton scores ≥6 and somatization was greater in those with a score ≥4.


  • “It is well-recognized that patients with joint hypermobility syndromes (eg, Ehlers-Danlos syndrome, Marfan) commonly have GI symptoms.” However, joint hypermobility is common —in this study’s healthy control group 36% had a score ≥4 and 9% had a score ≥6.
  • This study is in agreement with a school-based study (n=136) (M Saps et al. JPGN 2018; 66: 387-90).
  • Limitations: This study population had a median age of ~9.5 years; thus, these findings need to be determined in an older children

My take: There does not appear to be an increased risk of functional GI disorders in children with joint hypermobility. Thus, looking for joint laxity/hypermobility in children with abdominal pain is not needed.

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Also, a link to Dr. Roy (Benaroch).  Roy is an Atlanta pediatrician and he explains, with the help of Batman and Luigi, the term ‘index’ case and when one is considered exposed: Dr. Roy Covid Pathway

AGA Recommendations for Management of Functional Symptoms in Patients with Inflammatory Bowel Disease

Full text: AGA Clinical Practice Update on Functional Gastrointestinal Symptoms in Patients With Inflammatory Bowel Disease: Expert Review (JF Columbel et al. Clin Gastroenterol Hepatol 2019; 17: 380-90).

My take: Overall, this article presents a concise review of a tricky problem and appropiriate management.  The algorithm, tables and figures are useful.

Best practice advice 1: A stepwise approach to rule-out ongoing inflammatory activity should be followed in IBD patients with persistent GI symptoms (measurement of fecal calprotectin, endoscopy with biopsy, cross-sectional imaging).

In the report, the authors note that endoscopy and cross-sectional imaging are not needed in all patients; mainly in patients with a suspected flare based on presentation, calprotectin, and blood work.

Best practice advice 2: In those patients with indeterminate fecal calprotectin levels and mild symptoms, clinicians may consider serial calprotectin monitoring to facilitate anticipatory management.

Best practice advice 3: Anatomic abnormalities or structural complications should be considered in patients with obstructive symptoms including abdominal distention, pain, nausea and vomiting, obstipation or constipation.

Best practice advice 4: Alternative pathophysiologic mechanisms should be considered and evaluated (small intestinal bacterial overgrowth, bile acid diarrhea, carbohydrate intolerance, chronic pancreatitis) based on predominant symptom patterns.

Best practice advice 5: A low FODMAP diet may be offered for management of functional GI symptoms in IBD with careful attention to nutritional adequacy.

Best practice advice 6: Psychological therapies (cognitive behavioural therapy, hypnotherapy, mindfulness therapy) should be considered in IBD patients with functional symptoms.

Best practice advice 7: Osmotic and stimulant laxative should be offered to IBD patients with chronic constipation.

Best practice advice 8: Hypomotility agents or bile-acid sequestrants may be used for chronic diarrhea in quiescent IBD.

Best practice advice 9: Antispasmodics, neuropathic-directed agents, and anti-depressants should be used for functional pain in IBD while use of opiates should be avoided.

Best practice advice 10: Probiotics may be considered for treatment of functional symptoms in IBD.

Best practice advice 11: Pelvic floor therapy should be offered to IBD patients with evidence of an underlying defecatory disorder.

Best practice advice 12: Until further evidence is available, fecal microbiota transplant should not be offered for treatment of functional GI symptoms in IBD.

Best practice advice 13: Physical exercise should be encourage in IBD patients with functional GI symptoms.

Best practice advice 14: Until further evidence is available, complementary and alternative therapies should not be routinely offered for functional symptoms in IBD.


Joint Mobility –Not Associated with Increased Functional GI Disorders

According to a recent study (M Saps et al. JPGN 2018; 66: 387-90), joint hypermobility is not associated with an increased risk of functional gastrointestinal disorders (FGIDs).

From a school-based study of 654 children from a public school in Cali, Columbia, 148 (22.6%) were identified as having an FGID. Among this group, 136 children participated in the study along with 136 age/sex-matched healthy controls. Joint laxity was assessed to establish a Beighton score.

Key finding:

  • There was no significant difference in joint laxity between the FGID group and the control group, with OR of 1.03.

The implication of this study is that previous associations between joint hypermobility (JH) and FGIDs could be due to selection bias at tertiary care centers.  Alternatively, “it is possible that the association between FGIDs and JH exists, but it is only limited to a subset of patients that consult at specialized clinics.”

My take: This article challenges the idea that JH increases the risk of FGID.  Based on this study, if JH is a risk factor, it is hard to detect in a general population.

Related blog post:


Amber Cove, Dominican Republic