CLINICAL REVIEW

Functional Abdominal Cramping Pain

Expert Practical Guidance
Stefan Müller-Lissner, MD,* Viola Andresen, MD,†
Maura Corsetti, MD, PhD,‡§ Luis Bustos Fernández, MD,∥
Sylvie Forestier, MD,¶ Fabio Pace, MD, PhD,#
and Miguel A. Valdovinos, MD**

potential structural disease; the recognition of known causes that

Abstract: Functional abdominal cramping pain (FACP) is a com- might be addressed through lifestyle adjustment; and the central
mon complaint, which may present either on its own or in associ- role of antispasmodics in the treatment of FACP. The proposed
ation with a functional gastrointestinal disorder. It is likely caused algorithm is intended to assist physicians in reaching a meaningful
by a variety of, probably partly unknown, etiologies. Effective diagnostic endpoint based on patient-reported symptoms of FACP.
management of FACP can be challenging owing to the lack of We also discuss how this algorithm may be adapted for use by
usable diagnostic tools and the availability of a diverse range of pharmacists and patients.
treatment approaches. Practical guidance for their selection and use
is limited. The objective of this article is to present a working def- Key Words: functional abdominal cramping pain, functional gas-
inition of FACP based on expert consensus, and to propose prac- trointestinal disorder, antispasmodic, spasmolytic, primary care
tical strategies for the diagnosis and management of this condition
for physicians, pharmacists, and patients. A panel of experts on
(J Clin Gastroenterol 2022;56:844–852)
functional gastrointestinal disorders was convened to participate in
workshop activities aimed at defining FACP and agreeing upon a EXECUTIVE SUMMARY OF STATEMENTS AND
recommended sequence of diagnostic criteria and management RECOMMENDATIONS
recommendations. The key principles forming the foundation of the
definition of FACP and suggested management algorithms include Background
the primacy of cramping pain as the distinguishing symptom; the Functional abdominal cramping pain (FACP) is a com-
importance of recognizing and acting upon alarm signals of mon complaint that may present on its own or as a predom-
inant symptom of a functional gastrointestinal disorder
From the *Berlin, Germany; †Israelitisches Krankenhaus Hamburg, (FGID). Despite the studies suggesting a high prevalence of
Hamburg, Germany; ‡NIHR Nottingham Biomedical Research FACP in the general population, the Rome classification for
Centre, Nottingham University Hospitals NHS Trust; §School of
Medicine, University of Nottingham and Nottingham Digestive FGIDs does not consider it to be a discrete symptomatic entity.
Diseases Centre, Translational Medical Science, University of
Nottingham, Nottingham, UK; ∥Instituto Bustos Fernández, Definition
Buenos Aires, Argentina; ¶Sanofi, Gentilly, France; #Bolognini The expert panel proposes the following definition for
Hospital, Seriate and University of Milan, Milan, Italy; and FACP, as reported by patients with or without a diagnosed
**Instituto Nacional de Ciencias Médicas y Nutrición “Salvador
Zubirán,” Tlalpan, Mexico. FGID:
Medical writing support for the development of this manuscript, under
the direction of the authors, was provided by Ian C Grieve, PhD, of “FACP refers to the sudden occurrence of mild-to-
Ashfield MedComms, an Inizio company, and was funded by Sanofi. moderate, undulating, and recurring cramping pain in any
The authors received consultant fees for their participation in the expert part of the abdomen, lasting for seconds to minutes or up to
meeting but declare that the research was conducted in the absence of a few hours, in the absence of any “red flag” signs/symptoms
financial relationships that could be construed as a potential conflict
of interest. S.M.-L. has acted as a consultant for Sanofi. V.A. has of structural organic disease or any strong association with
acted as a consultant and/or speaker for Arena Pharmaceuticals, defecation (which might indicate irritable bowel syndrome
Bayer, Dr. Falk Pharma, Hexal, Kyowa Kirin, Medicef Pharma, [IBS]), and typically not significantly interfering with daily
Shionogi, 4M Medical, and Sanofi. M.C. has acted as a consultant for activities.”
Arena Pharmaceuticals, RB Pharmaceuticals, Mayoly Spindler
Pharma, and Sanofi. She is also coprincipal investigator on a Sanofi- FACP could be perceived as reflecting part of the IBS
sponsored clinical trial. L.B.F. has acted as a speaker for Sanofi. F.P. spectrum but without a strong association with bowel
has acted as a speaker for Alfasigma. M.A.V. has acted as a speaker
for Sanofi. S.F. is an employee of Sanofi. irregularities. In situations where FACP is tightly linked
Address correspondence to: Stefan Müller-Lissner, MD, Eisenacher Str. with abnormalities of bowel evacuation, a diagnosis of IBS
103D, Berlin 10781, Germany (e-mail: [email protected]). should be suspected, provided that patients fulfill the Rome
Supplemental Digital Content is available for this article. Direct URL IV diagnostic criteria.
citations appear in the printed text and are provided in the HTML
and PDF versions of this article on the journal’s website, www.jcge.
com.
Statements and Recommendations
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Burden of FACP
Inc. This is an open access article distributed under the terms of the
Creative Commons Attribution-Non Commercial-No Derivatives
License 4.0 (CCBY-NC-ND), where it is permissible to download  Health care professionals, including specialists, primary
and share the work provided it is properly cited. The work cannot be care physicians/general practitioners, and pharmacists,
changed in any way or used commercially without permission from should be aware of FACP, the impact it can have on
the journal.
DOI: 10.1097/MCG.0000000000001764 sufferers, and how to manage symptoms.

844 | www.jcge.com J Clin Gastroenterol  Volume 56, Number 10, November/December 2022
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J Clin Gastroenterol  Volume 56, Number 10, November/December 2022 Functional Abdominal Cramping Pain Guidance

Causes of FACP recommendations for the general diagnosis and symptom-

atic management of FACP are lacking.
 The causes of FACP in FGIDs are unclear but are The lack of guidance on how to diagnose and manage
probably multifactorial. FACP reflects the absence of a standard, accepted defi-
nition, and limited focused literature on this complaint.
Diagnosis and Investigation of FACP in Primary Care The Rome Foundation has developed and updated its own
criteria, currently up to Rome IV, to diagnose FGIDs,
 When evaluating FACP in primary care, the first step is including those associated with FACP, such as IBS,
to rule out “red flags” (alarm signals) of structural functional dyspepsia, biliary pain, postprandial distress
organic disease, which necessitate referral to a specialist. syndrome, epigastric pain syndrome, and narcotic bowel
 A detailed evaluation of family history, medication, syndrome (also referred to as opioid-induced gastro-
characteristics of pain, and eating/bowel habits should be intestinal hyperalgesia).1,2,7,13,14 However, although the
undertaken in all patients presenting to primary care with Rome criteria are a useful tool for gastroenterologists and
FACP symptoms. researchers, they do not fully capture the presentation of
 In selected cases and at the discretion of the doctor, a FACP seen in everyday practice, nor are they practical
physical examination (including bowel sounds and digital enough to be used routinely by primary care physicians
rectal examination), laboratory tests, and psychosocial (PCPs)/general practitioners (GPs), pharmacists, or
assessment may also be appropriate. Abdominal ultra- patients, whose primary objective—once structural,
sound investigations may be helpful. organic causation has been ruled out—is symptom allevi-
ation. The present expert guidance attempts to address
these issues by providing a consensus definition for FACP
Clinical Management of FACP in Primary Care and by presenting recommendations for its diagnosis and
clinical management, with a focus on primary care and
 Mild, infrequent episodes of FACP may only require self-management. To complement these recommendations,
reassurance and advice (including avoidance of trigger practical, easy-to-use algorithms have been constructed to
foods), whereas more intensive and/or frequent episodes aid physicians, pharmacists, and patients themselves in
usually require therapeutic intervention. identifying and managing FACP.
 Many patients with FACP who present to primary care
may require empirical treatment with an antispasmodic,
the choice of which will depend on local availability and
individual preference. If the first drug does not provide METHODS
adequate symptom relief, it might be worthwhile to try an A panel of well-recognized experts in the field of
alternative antispasmodic. FGIDs, based in Europe and Latin America, was con-
 Patients who obtain little or no relief from their vened for the purpose of addressing the agreed-upon
FACP with an antispasmodic may benefit from addi- unmet need for better guidance for diagnosing and treating
tional analgesia, for example, with acetaminophen FACP, as recalled by individuals who do not meet the
(paracetamol). criteria for a diagnosis of IBS under the Rome (IV) cri-
 Patients with centrally mediated abdominal pain syn- teria. The focus of the meetings was on primary care
drome may respond to low doses of tricyclic antidepres- management of FACP, as this reflects the main approach
sants or selective serotonin reuptake inhibitors, or to the used in Europe and Southern/Latin America, of which the
neuromodulator pregabalin. authors have expert knowledge. However, over-the-coun-
 Relaxation training and targeted psychological interven- ter (pharmacist- and patient-led) self-management was
tions may be the helpful adjunctive therapies for selected also reviewed.
patients who suffer from stress and/or have preexisting The panel met twice to discuss and agree on the
psychiatric comorbidities. definition of FACP. During the first meeting, the panel
participated in workshop activities to agree upon a defi-
Self-management of FACP nition of FACP and to discuss its diagnosis and man-
agement. The format allowed time for all participants to
 Self-management of FACP using over-the-counter prod- input their views and was followed by group discussion
ucts is appropriate for many patients with mild, non- and final agreement. To facilitate diagnosis and manage-
persistent symptoms. ment, 3 draft algorithms (targeted at PCPs/GPs, phar-
 To enable better self-care, patients and pharmacists macists, and patients, respectively) were also developed,
require education and information on signs and symp- taking into consideration the professional guidelines, the
toms to be aware of, and which treatments to use. quality of the clinical evidence for specific management
strategies, and the panel’s own experience. The panel then
participated in a second meeting to discuss further
INTRODUCTION refinement and finalization of the algorithms. Consensus
Functional abdominal cramping pain (FACP) is fre- statements and recommendations from these expert
quently encountered in the general population. It may meetings are presented. The panel note that, because of a
present either on its own or in association with a functional lack of targeted literature on FACP, there was a need to
gastrointestinal disorder (FGID; also known as a disorder refer closely to the data on FGIDs, especially IBS, and
of gut-brain interaction), such as irritable bowel syndrome many of the statements and recommendations provided
(IBS), functional dyspepsia, and biliary pain.1,2 Although here are, therefore, similar to those in published guidelines
national and international guidelines exist for managing the for the diagnosis and management of abdominal pain in
symptoms of IBS, including the abdominal pain,3–12 patients with FGIDs.

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Müller-Lissner et al J Clin Gastroenterol  Volume 56, Number 10, November/December 2022

BURDEN OF FACP FACP could be perceived as reflecting part of the IBS

spectrum but without a strong association with bowel irregu-
larities. In situations where FACP is tightly linked with
Statement: abnormalities of bowel evacuation, a diagnosis of IBS should be
 Health care professionals, including specialists, PCPs/ suspected, provided that patients fulfill the Rome IV diagnostic
GPs, and pharmacists, should be aware of FACP, the criteria.
impact it can have on sufferers, and how to manage
symptoms. CAUSES OF FACP

Comments Statement:
FGIDs, many of which may be associated with FACP,  The causes of FACP in FGIDs are unclear but are
are extremely common and can have a negative impact on the probably multifactorial.
quality of life of sufferers and incur a substantial health care
burden in terms of an increase in the consumption of medical
therapies, a greater requirement for abdominal surgery, and Comments
additional medical consultations/referrals.15–18 The recently Although there is little information on the causes of FACP,
published global Rome Foundation epidemiological study of it is the consensus view of the panel that mechanisms that
73,076 people, based on the new Rome IV classification, underlie these symptoms are probably similar to those reported
found that 40.3% of respondents who completed the internet for the IBS spectrum. As in IBS, FACP, which may be periph-
survey and 20.7% of those who completed the household erally and/or centrally mediated, may result from an interplay
survey met the criteria for at least 1 FGID.15 The prevalence between psychological stress (leading to a dysregulated gut-brain
of FGIDs was 1.3 to 1.7 times higher in women than in men. interaction), mucosal immunity (immune activation resulting in
FACP is frequently reported by patients either on its chronic low-grade inflammation), visceral hypersensitivity, dys-
own or in conjunction with FGIDs. The true prevalence of biosis, and gut dysmotility (Fig. 1).25–27 The susceptibility of
FACP, in isolation from bowel movement irregularities, is individuals to FACP and their experience of symptoms may
difficult to ascertain because, up until now, there has been depend on both genetic predisposition and external aggravators.
no uniform definition of FACP. Although definitions do Data in FGIDs indicate that one of the most important
vary, survey data suggest that the prevalence of FACP in the external factors affecting gastrointestinal function and
general population may range from 10% to 46%.19,20 In an symptoms, including FACP, is stress.28–31 Although it is
internet-based, observational study of 720 women with beyond the scope of this article to review this topic, there is
abdominal pain, cramping, and discomfort, symptoms of evidence that stress promotes delayed gastric emptying and
FACP were reported to interfere with some respondents’ accelerated colonic transit,29,32 and that the stress response
daily activities (44% reported disruption very often/often), in the gut is mediated, largely, by corticotropin-releasing
work and sleep quality, and social activities.21 Furthermore, factor and its downstream signaling pathways.33,34
in a large survey of IBS sufferers conducted by the American
Gastroenterology Association, abdominal pain was identi-
Food Gas
fied as one of the most bothersome disease symptoms and a Symptom(s) Complaints
symptom that should be addressed.22 As well as impacting
on patient quality of life,21,22 abdominal pain is also a most Peripheral Normal motility
Stress
common reason for primary care consultation, with a mean signal and sensitivity
consultation prevalence of 2.8% reported in a systematic
review of 14 symptom-evaluating studies on abdominal pain Abnormal motility Anticipation or
in the general practice setting.23 and sensitivity chronicity

DEFINITION OF FACP Microbiota

The latest Rome IV criteria focus on the diagnosis

and overall management of FGIDs rather than on the
specific presentation and symptomatic treatment of FACP Gut wall
Spinal synapsis
Affective rating/coping
(Supplemental Digital Content Table 1, http://links.lww. (vagus nerve)
com/JCG/A890).1,2,7,13,24 Furthermore, although FACP Thresholds to overcome
has been reported in the literature without association Abdominal periphery Gut–brain axis Central pain processing
with a particular disorder,19–21 there is no standardized
definition. We, therefore, propose the following definition FIGURE 1. Current understanding of the pathophysiology of
for FACP: abdominal pain in functional gastrointestinal disorders. A
peripheral signal is a prerequisite, that is, the pain is not merely a
psychological event. This signal may originate from the intestinal
Definition of FACP: contents (food or gas) or from changes in gastrointestinal motility
FACP refers to the sudden occurrence of mild-to-moderate, and sensitivity; the latter may be altered by stress. To be recog-
undulating, and recurring cramping pain in any part of the abdomen, nized by the individual, the signal must overcome some thresh-
lasting for seconds to minutes or up to a few hours, in the absence of olds: sensation within the gut wall, spinal synapsis, and—to be
any “red flag” signs/symptoms of structural organic disease or any experienced as “uncomfortable”—the affective rating (the latter
strong association with defecation (which might indicate IBS), and again being impacted by stress). Gut wall sensation and spinal
typically not significantly interfering with daily activities. synapsis may be lowered by the microbiota and anticipation or
chronicity, respectively.

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J Clin Gastroenterol  Volume 56, Number 10, November/December 2022 Functional Abdominal Cramping Pain Guidance

Gastrointestinal function and symptoms can also be the FACP. We recommend that the assessment includes an
affected by eating habits and food intake. Although it is cur- evaluation of family history (especially for malignancy, gastro-
rently unknown whether FACP itself relates directly to eating intestinal diseases, and other conditions that could affect their
patterns and/or the ingestion of specific trigger foods or food management), current and recent medication, characteristics of
components, it is worth noting that, in many patients with IBS- pain (nature, location, duration, quality, frequency, and
related abdominal pain, diet and nutrition seem to have some severity), and eating/bowel habits (including known food aller-
role in evoking and sustaining the low-grade inflammation in gies, intolerances, and triggers). In selected patients and at the
the abdominal tissues and in altering the gut microbiota.26,27 discretion of the doctor, a physical examination (including
bowel sounds and digital rectal examination) and limited lab-
DIAGNOSIS AND INVESTIGATION oratory tests may be appropriate, and psychosocial assessment
OF FACP IN PRIMARY CARE may also be helpful, particularly if the patient has preexisting
psychiatric comorbidities or there are indicators of significant
Ruling Out Organic Pathology psychological stress.11,35,37 The physical examination should
assess the pain location and whether there is a palpable mass,
abnormal or absent bowel sounds, rebound tenderness, rigidity/
Recommendations:
resistance, distension, and/or guarding. Experience in IBS shows
 When evaluating FACP in primary care, the first step is
that relevant laboratory tests might include complete blood cell
to rule out “red flags” (alarm signals) of structural
counts and other targeted blood tests (eg, erythrocyte sed-
organic disease, which necessitate referral to a specialist.
imentation rate, C-reactive protein, and/or celiac serology),
thyroid and liver function tests, and stool studies (eg, fecal cal-
Comments protectin and/or occult blood test), as indicated.5,11,35,38
When a patient first presents to primary care with Abdominal ultrasound investigations can sometimes be helpful
symptoms of FACP, the first step is to rule out potentially and are cheap and simple to undertake in most settings.39 There
serious organic disease. Key red flag signs and symptoms that are also certain other signs and symptoms that may require
could indicate structural disease are summarized in Table 1. additional evaluation. For example, for pain in women that
Patients presenting with any indicators of organic disease seems to be related to the menses, a gynecologic evaluation
require referral to a specialist for further investigation. should be considered.38 Similarly, for pain brought on by
physical exertion, a cardiology assessment should be sought. If
Investigations and Diagnosis the initial investigations raise concerns or are equivocal, referral
for a computerized axial tomography scan might be considered.
Assuming none of the red flag signs/symptoms are pres-
Recommendations: ent and no abnormalities are identified at the physical exami-
 A detailed evaluation of family history, medication, nation, laboratory tests, or other investigations, a diagnosis of
characteristics of pain, and eating/bowel habits should FACP may be considered if the symptoms are described by the
be undertaken in all patients presenting to primary present definition. If the FACP is tightly related to changes in
care with FACP symptoms. bowel evacuation, IBS is the most probable diagnosis and
 In selected cases and at the discretion of the doctor, a should be confirmed using the Rome IV criteria.
physical examination (including bowel sounds and
digital rectal examination), laboratory tests, and CLINICAL MANAGEMENT OF FACP
psychosocial assessment may also be appropriate. IN PRIMARY CARE
Abdominal ultrasound investigations may be helpful.

Recommendations:
Comments  Mild, infrequent episodes of FACP may only require
As with FGIDs in general, a comprehensive patient reassurance and advice (including avoidance of trigger
assessment is needed to rule out red flags and to characterize foods), whereas more intensive and/or frequent
episodes usually require therapeutic intervention.
TABLE 1. Red Flag (Alarm) Signs That May Be Present in Patients With  Many patients with FACP who present to primary care
Functional Abdominal Cramping Pain (List Not Exhaustive)10,11,35–38 may require empirical treatment with an antispasmodic,
the choice of which will depend on local availability and
“Red flag” signs individual preference. If the first drug does not provide
Family history of a gastrointestinal disease with a heritable
component, eg,
adequate symptom relief, it might be worthwhile to try
Colorectal cancer an alternative antispasmodic.
Inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis)  Patients who obtain little or no relief from their FACP
Celiac disease with an antispasmodic may benefit from additional
Recent weight loss that cannot be readily explained, or loss of appetite analgesia, for example, with acetaminophen (paracetamol).
Recent onset of anemia, or of unusual pale appearance (pallor)  Patients with centrally mediated abdominal pain
Recent onset of fever syndrome may respond to low doses of tricyclic
Presence of unexplained blood in stools antidepressants or selective serotonin reuptake inhib-
Presence of abnormal abdominal mass, or of fluid buildup in the itors, or to the neuromodulator pregabalin.
abdomen (ascites)
Significant worsening of symptoms at night
 Relaxation training and targeted psychological inter-
Recent marked change in symptoms ventions may be the helpful adjunctive therapies for
Persistent vomiting or diarrhea selected patients who suffer from stress and/or have
Onset of symptoms in patients aged 50 y or older preexisting psychiatric comorbidities.

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Müller-Lissner et al J Clin Gastroenterol  Volume 56, Number 10, November/December 2022

Comments head-to-head trials and sparsity of recent data, limited evi-

The management of FACP depends on the intensity dence exists to support differentiation of antispasmodic
and frequency of presentation. The occurrence of mild, therapies. There are also very few studies, which have spe-
infrequent episodes often only requires reassurance cifically investigated antispasmodics as a treatment
and advice, whereas the presentation of more intensive for FACP.
and/or frequent symptoms will usually necessitate ther- Clinical evidence for the benefit of antispasmodic
apeutic intervention. It should be noted that FACP in therapy in treating FACP as the primary symptom comes
patients with IBS (ie, FACP associated with changes in mainly from studies of hyoscine butylbromide.40,41,49,50 Two
bowel habits or stool form, according to Rome IV cri- randomized, double-blind, placebo-controlled trials have
teria) should be managed in line with current IBS demonstrated the efficacy, albeit limited, of hyoscine
guidelines.3–11 butylbromide (given in limited-duration courses or as on-
Among all patients presenting with FACP, there are demand treatment) in reducing the intensity and frequency
many considerations for determining the optimal approach of abdominal pain, with few side effects, in patients defined
to symptom management. Patient-specific factors to be by the presence of FACP symptoms.40,41 In the first of these
considered include age, sex, onset of pain, location of pain, studies, involving 1637 patients with recurrent, crampy
duration of pain, pain variations, quality of pain, con- abdominal pain, hyoscine butylbromide was significantly
comitant symptoms, lifestyle, aggravators, and relieving more efficacious than placebo in improving pain intensity
factors. Patients with mild FACP can usually be managed (measured on a 10 cm visual analog scale; adjusted mean
by reassuring them that the cause of their pain is not change from baseline, −2.3 vs. −1.9 cm, respectively,
sinister and by advising them to avoid foods or drinks that P < 0.0001) and frequency [measured on a verbal rating
may trigger and/or exacerbate symptoms and to avoid scale (range: 0–3); adjusted mean change from baseline,
stress. Patients may be advised to return to their usual diet −0.7 vs. −0.5, respectively, P < 0.0001] when given for a
if a dietary elimination trial is unsuccessful. As recom- limited period of 3 weeks.40 In the second study of 175
mended for IBS patients,11 it also seems sensible to provide patients with self-reported, recurrent, functional, cramping
general guidance on maintaining a healthy diet and abdominal pain, on-demand hyoscine butylbromide sig-
lifestyle. nificantly reduced the intensity of pain (measured on an
Although an improvement in diet and lifestyle is 11-point numerical pain rating scale) experienced by
likely to benefit the overall health of all patients, many patients during 2 distinct episodes compared with placebo
patients with FACP may also require empirical medical (adjusted mean difference vs. placebo in change from
treatment, usually with antispasmodics. These therapies baseline for episode 1, −0.7, P = 0.016).41 Positive effects on
are the most suitable for alleviating FACP, as they act quality of life have also been reported for hyoscine butyl-
directly on the smooth muscle of the gut to suppress the bromide treatment among patients with FACP, with greater
muscle cramps and spasticity that underlie the abdominal improvements observed compared with standard analgesia
pain. They have also been shown to be efficacious in regarding patients’ ability to carry out daily activities, work
patients primarily defined by the presence of FACP quality, and symptoms experienced during stressful
symptoms.40,41 This approach, thus, contrasts with the situations.21
global treatment of IBS, where the goal is to reduce overall In instances where an antispasmodic agent seems to
symptoms including abdominal pain, distention, bloating, be ineffective, and in the absence of an identified organic
indigestion, and altered bowel patterns (constipation and/ cause of FACP, it might be worthwhile to trial another
or diarrhea).12 Most patients with FACP can be managed antispasmodic with a different mechanism of action
with on-demand medication but those with frequent or before attempting to introduce other treatment modal-
more severe symptoms may require a limited course of ities. Although switching from 1 antispasmodic to another
treatment. The ideal drug should be suitable for on- has not been evaluated, such trial and error seems justified
demand use and have a fast onset of action with a long- if the pharmacology of the 2 agents is different. Further
lasting effect, minimal systemic absorption, and few side treatment options at this point may include the herbal
effects.42 The choice of antispasmodic therapy will usually medicinal products, peppermint oil or STW 5. Peppermint
depend on local availability and individual preference. oil has antispasmodic properties and multiple clinical
Types of antispasmodic medications, which are available studies have shown that it can reduce abdominal pain in
as over-the-counter or prescription only products, patients with IBS.4,43,44,47,48,51 Across Europe, pepper-
depending on the market, include (1) antimuscarinics, for mint oil is indicated as a “herbal medicinal product for
example, hyoscine butylbromide, dicycloverine hydro- the symptomatic relief of minor spasms of the gastro-
chloride (dicyclomine), and cimetropium; (2) the phos- intestinal tract, flatulence and abdominal pain, especially
phodiesterase inhibitors drotaverine and papaverine; (3) in patients with IBS.”52 Evidence supporting the clinical
the sodium channel blocker mebeverine; (4) the peripheral efficacy/effectiveness of another herbal treatment, STW 5,
opiate receptor agonist trimebutine; (5) the calcium to reduce abdominal pain is also available, but the data
channel blockers otilonium and pinaverium; (6) the direct are less compelling than for antispasmodics (including
smooth muscle relaxant alverine (often given in combina- peppermint oil), and mainly derived from a small
tion with the antifoaming agent simethicone, which is used number of studies in IBS or functional dyspepsia.21,53–55
to reduce bloating, discomfort, and/or pain caused by Notably, rare cases of hepatoxicity leading to liver failure
excessive gas); and (7) the herbal medicinal product, have been reported during STW 5 treatment,56,57
peppermint oil. resulting a label change to exclude its use in individuals
Multiple meta-analyses and randomized controlled with liver disease, as well as in pregnant or breastfeeding
trials have shown that antispasmodic drugs are more effi- women.58
cacious than placebo at improving abdominal pain in Patients obtaining little or no relief from their FACP
patients with IBS.43–48 However, because of the lack of with antispasmodics may benefit from adjunctive analgesia

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J Clin Gastroenterol  Volume 56, Number 10, November/December 2022 Functional Abdominal Cramping Pain Guidance

treatment. Acetaminophen (paracetamol) has been shown to Comments

be more efficacious than placebo and similar to hyoscine Self-care of gastrointestinal symptoms that impact
butylbromide in reducing the intensity and frequency of quality of life, but which are not associated with a significant
recurrent crampy abdominal pain in a large-scale clinical impairment in a person’s ability to carry out daily activities
trial,40 and is an important, well-tolerated, and widely and are not associated with obvious symptoms of structural
available option for treating FACP. As FACP is unlikely to disease, is commonplace.19,38,42 Rates of health care seeking,
have the same pathophysiology in all afflicted patients, it is self-care (over-the-counter drug use), and overall medication
possible that patients responding to acetaminophen might not use among patients with symptoms of FACP do, never-
be the same as those responding to antispasmodic therapy. theless, vary across countries and regions.19,38,42 For
Nonsteroidal anti-inflammatory drugs, which are also com- example, greater use of medications for managing FACP
monly accessible, have been shown to be effective against
(comprising mainly over-the-counter products) has been
intense ambulatory cramping pain of gastrointestinal or reported in the United States and Latin America than in
genitourinary origin.59 However, these drugs are not appro- Europe (90% vs. 72%, respectively).19 Reasons for preferring
priate for most patients with mild-to-moderate FACP self-management approaches among patients with FACP
because of their poor gastrointestinal side-effect profiles.60 may include cultural differences in the perception of and
Opioid analgesics are best avoided, if possible, as their use response to symptoms, and limitations in access to drugs
can cause constipation, nausea, and vomiting, which may and physician care.38,42
worsen symptoms of FACP. There is also a high risk of
dependence and addiction with these drugs.61 Furthermore,
high acute doses or chronic use of opioids may lead to the
development of narcotic bowel syndrome, a FGID which, by
definition, is associated with abdominal pain.1 FACP
Patients with centrally mediated abdominal pain syndrome
(formerly known as functional abdominal pain syndrome)—a No alarm signs (‘red flags’), eg,
severely limiting FGID with a strong central component and • Weight loss
relative independence from motility disturbances, which presents • Anemia or striking pallor
as continuous, near continuous, or frequently recurrent • Persistent vomiting or diarrhea
abdominal pain lasting for at least 6 months24—may respond to • Rectal bleeding

low doses of tricyclic antidepressants or selective serotonin Yes

Related to menses (women)? Consider gynecology referral
reuptake inhibitors, or to the neuromodulator pregabalin. These
No
therapeutic options, which are common, effective treatments for Yes
Related to physical activity? Consider cardiology referral
many nongastrointestinal medical and functional central pain
No
syndromes,24 have been shown to reduce abdominal pain in
Normal physical findings and lab tests
patients with IBS (where abdominal pain is mediated through • No organ enlargement
both central and peripheral mechanisms),62 although any benefits • No pathologic resistance
must be weighed against the high likelihood of side effects.44,63–65 • Normal bowel sounds
Targeted psychological interventions, such as cognitive • No peritoneal signs
• Pain not in abdominal wall
behavioral therapy, multicomponent psychological therapy,
gut-directed hypnotherapy, and dynamic psychotherapy, Yes
Related to bowel evacuation? IBS is likely diagnosis
have been shown to be helpful adjunctive therapies in
No
managing abdominal pain in IBS11,63,65 and therefore may Yes
Mild, infrequent episodes? Provide advice/reassurance
have a wider application in FACP management. Such
No
interventions would be expected to be most helpful for Evoked by foods?
Yes
Avoidable?
patients with preexisting anxiety and/or depression. Relax-
ation training/activities may also benefit some patients Evoked by stress?
Yes Consider psychological
whose symptoms are triggered or worsened by stressful sit- interventions/
uations that cannot be avoided.63 relaxation training
Patients with FACP may also present with other co- Empiric medical treatment:
occurring gastrointestinal symptoms, such as constipation • 1st line: Antispasmodic
or diarrhea. Though they should not be ignored, there is • 2nd line: Alternative antispasmodic
little evidence that treating these symptoms and improving • 3rd line: Acetaminophen (paracetamol)
bowel habits will, in isolation, improve FACP.66,67
Non-responsive/chronic? Yes Consider low-dose TCAs/
SELF-MANAGEMENT OF FACP Likely centrally mediated SSRIs or pregabalin

FIGURE 2. Algorithm for the symptomatic management of FACP,

Recommendations: designed for use by physicians. FACP refers to the sudden
occurrence of mild-to-moderate, undulating, and recurring
 Self-management of FACP using over-the-counter cramping pain in any part of the abdomen, lasting for seconds to
products is appropriate for many patients with mild, minutes or up to a few hours, in the absence of any “red flag”
nonpersistent symptoms. signs/symptoms of structural organic disease or any strong asso-
 To enable better self-care, patients and pharmacists ciation with defecation (which might indicate IBS), and typically
require education and information on signs and not significantly interfering with daily activities. FACP indicates
symptoms to be aware of, and which treatments functional abdominal cramping pain; IBS, irritable bowel syn-
to use. drome; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic
antidepressant.

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Müller-Lissner et al J Clin Gastroenterol  Volume 56, Number 10, November/December 2022

Self-management of FACP typically involves the use of alterations, thus emphasizing the distinction between IBS
over-the-counter pharmaceuticals and/or nonpharmacologic (as defined by the Rome IV criteria) and the definition of
products, with or without consultation with a FACP proposed here. The algorithm also seeks to rule out
pharmacist.19,42 As self-management of FACP is so com- abdominal pain of gynecologic or cardiac origin. For
mon, particularly on first presentation of symptoms, both first-line treatment, antispasmodics are recommended for
patients and pharmacists require education and information patients whose symptoms fulfill the consensus definition of
on signs and symptoms to be aware of (including red flags FACP and who lack signals of a potential differential
that may necessitate a health care consultation) and which diagnosis or other avoidable explanatory factors. Addi-
treatments to use, which will vary depending on local tional treatment options are suggested for patients who fail
practice and preferences, and product availability. to achieve satisfactory symptom alleviation with first-line
antispasmodic therapy.
ALGORITHMS TO AID THE RECOGNITION In view of the prevalence of self-care among patients
AND MANAGEMENT OF FACP experiencing FACP, we propose how this algorithm might
A proposed algorithm for the optimal diagnosis and be adapted for pharmacists and patients to help support
management of FACP by physicians, considered by the improved self-management of FACP, raise awareness of
expert panel to be appropriate for use in primary care, is “red flag” signs/symptoms that should referral to or con-
presented in Figure 2. This algorithm is based on the sultation with an appropriate physician, and highlight
definition of FACP, and the management considerations alternative approaches that patients might not consider
outlined in the preceding sections. The starting point for intuitively (Figs. 3, 4). These algorithms could form the
the diagnosis is the core symptomatic manifestation of basis of the pharmacist and patient education needed to
FACP, pain with cramping characteristics, which is gen- facilitate the recognition and effective self-treatment
erally considered to arise from primary gastrointestinal of FACP.
dysfunction. To establish the diagnosis of FACP, the
critical first step is exclusion of a structural organic cause.
This can be achieved through the recognition of alarm
Do you experience abdominal
signals (“red flags”) related to other symptoms experienced cramping pain?
and/or the patient’s family history of disease, and by
considering the results of appropriate investigations, con- Yes
ducted as indicated by such signals. The algorithm con- Do you feel sick and/or experience
symptoms, such as...
siders the likelihood of an IBS diagnosis in cases where Yes
• Recent unintended weight loss?
FACP symptoms are associated with bowel habit • Paleness and feeling unwell?
• Persistent vomiting or diarrhea?
• Blood in your stools?
FACP
No
Is your pain associated with your Yes
Accompanied by any other Yes
period (women)?
notable changes?
No Consult your
No Yes or doctor
Yes Is your pain associated with any
Recommend medical Not sure
Related to period (women)? kind of physical activity?
consultation
No No
Yes
Related to physical activity? Is your pain debilitating OR does it Yes
No interfere with your daily activities
Yes OR does it wake you up at night?
High pain intensity?
No
No
Yes Counsel – IBS is Have you ever experienced this
Related to bowel evacuation? No
probable diagnosis type of pain before or pain of this
No high intensity?
Yes
Pain evoked by certain foods? Suggest avoidance Yes
No Is your pain associated with Yes You may have IBS –
defecation, eg, is it eased by consult your
Treatment with antispasmodic is justified passing a stool? pharmacist or doctor
• Acetaminophen (paracetamol) may also be beneficial
No

Yes Is your pain made worse by eating Yes Try to avoid foods that
Recommend medical
Non-responsive/chronic? certain foods? trigger your symptoms
consultation
No
FIGURE 3. Algorithm for the symptomatic management of FACP, Is your pain made worse by certain Yes Try relaxation training/
designed for use by pharmacists. FACP refers to the sudden unavoidable stressful situations? activities
occurrence of mild-to-moderate, undulating, and recurring
No
cramping pain in any part of the abdomen, lasting for seconds to
minutes or up to a few hours, in the absence of any “red flag” Ask your pharmacist to try a so-called antispasmodic
signs/symptoms of structural organic disease or any strong asso- • Acetaminophen (paracetamol) may also help with your pain
ciation with defecation (which might indicate IBS), and typically
not significantly interfering with daily activities. FACP indicates FIGURE 4. Algorithm for the symptomatic management of FACP,
functional abdominal cramping pain; IBS, irritable bowel designed to aid patient self-care. FACP indicates functional
syndrome. abdominal cramping pain; IBS, irritable bowel syndrome.

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J Clin Gastroenterol  Volume 56, Number 10, November/December 2022 Functional Abdominal Cramping Pain Guidance

CONCLUSIONS 10. Carmona-Sánchez R, Icaza-Chávez ME, Bielsa-Fernández

FACP is a common presentation, occurring either MV, et al. The Mexican consensus on irritable bowel syndrome.
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