What are the diagnostic criteria and treatment options for a patient with suspected centrally mediated (centralized) abdominal pain syndrome, with a history of chronic pain, anxiety, or depression, and no clear evidence of underlying medical conditions such as inflammatory bowel disease or gastroesophageal reflux disease?

Diagnosis of Centrally Mediated Abdominal Pain Syndrome

Centrally mediated abdominal pain syndrome (CAPS) is diagnosed when chronic or recurrent abdominal pain occurs continuously or nearly continuously for at least 6 months, is not exclusively related to physiological events (eating, defecation, menses), shows poor relationship to gut function, and is associated with loss of daily functioning—all in the absence of structural or biochemical abnormalities that explain the pain. 1, 2

Core Diagnostic Criteria

• Pain characteristics: The abdominal pain must be present continuously or nearly continuously for at least 6 months, distinguishing CAPS from episodic functional disorders like IBS 2
• Independence from gut function: Unlike IBS where pain correlates with bowel movements, CAPS pain shows minimal relationship to defecation, eating, or other physiological GI events 2
• Functional impairment: The pain must cause significant loss of daily functioning, often resulting in frequent healthcare utilization, work disability, or social withdrawal 1, 3
• Central pain mechanisms: CAPS results from central sensitization with disinhibition of pain signals rather than increased peripheral afferent excitability, meaning the brain's pain processing system amplifies signals independent of ongoing tissue damage 2

Clinical Assessment Strategy

Behavioral Indicators During Examination

• The closed eyes sign: When a patient closes their eyes during abdominal palpation, this behavioral indicator reflects hypervigilance to pain and central sensitization mechanisms, signaling that central factors are maintaining and amplifying the pain 1
• This sign should prompt immediate shift toward neuromodulator therapy and brain-gut behavioral interventions rather than continued investigation for organic disease 1

Essential History Elements

• Pain pattern specifics: Document whether pain is truly constant versus intermittent, as CAPS requires near-continuous pain unlike the episodic pain of IBS 2
• Relationship to physiological triggers: Explicitly ask if pain changes with eating, defecation, or menstruation—minimal relationship supports CAPS diagnosis 2
• Prior chronic pain conditions: History of fibromyalgia, chronic headaches, or other chronic pain syndromes strongly predicts centrally mediated mechanisms, with 20-50% of IBS patients having comorbid fibromyalgia and 77% of fibromyalgia patients having lifetime IBS 1, 4
• Psychological comorbidities: Depression occurs in 88.9% and anxiety/panic disorders in 38.9% of CAPS patients requiring frequent hospitalization 3
• Early-life adversity or trauma: Post-traumatic stress disorder is present in 27.8% of severe CAPS cases, and history of childhood or adult abuse predicts centrally mediated pain 5, 3
• Catastrophizing behaviors: Assess for excessive worry about pain, belief that pain signals serious disease despite negative workup, and pain-related fear avoidance 1
• Healthcare utilization patterns: CAPS patients demonstrate abnormal illness behavior with multiple somatic complaints, frequent consultations for minor illnesses, and inappropriate surgery history 5, 3

Physical Examination Focus

• Abdominal examination: Assess for objective findings suggesting organic pathology such as masses, distension, or peritoneal signs—their absence supports functional diagnosis 5
• Rectal examination: Inspect for perianal disease, assess sphincter tone, and check for masses to exclude structural pathology 5
• Observe pain behaviors: Note whether patient closes eyes during palpation, exhibits exaggerated pain responses, or shows hypervigilance 1

Laboratory and Diagnostic Testing

Initial Screening Panel (One-Time Only)

• Complete blood count: Screen for anemia suggesting bleeding or malabsorption 1, 6
• Inflammatory markers: C-reactive protein or ESR to exclude inflammatory bowel disease 5, 1, 6
• Comprehensive metabolic panel: Assess liver function and nutritional status 6
• Celiac serology: Tissue transglutaminase IgA with total IgA to exclude celiac disease 6, 4
• Fecal calprotectin: If <100 μg/g, this supports functional diagnosis and argues against IBD 4

When to Stop Testing

• Once basic laboratory workup excludes organic pathology, stop further invasive testing when functional diagnosis is established 1
• No therapeutic decision should be taken based on clinical consideration alone in IBD patients, but in suspected CAPS without IBD history, repetitive testing after initial negative workup is not recommended 5, 7
• Continued investigation after negative initial workup increases risk of iatrogenic harm from unnecessary procedures and reinforces patient belief in undiagnosed organic disease 1

Exclusion of Organic Disease

Alarm Features Requiring Further Investigation

• Unintentional weight loss: Suggests organic disease rather than functional disorder 4
• Rectal bleeding: Requires colonoscopy to exclude inflammatory or neoplastic disease 4
• Nocturnal symptoms: Diarrhea or pain that awakens patient from sleep suggests organic pathology 5, 4
• Fever: Indicates possible inflammatory or infectious process 5
• Acute symptom onset: In previously well-controlled patients, maintain high suspicion for underlying inflammatory activity 5
• High volume or high frequency diarrhea: Suggests secretory rather than functional etiology 5
• Anorexia: Strongly suggests organic disease rather than functional bowel disorder 4

Conditions to Definitively Exclude

• Inflammatory bowel disease: Use inflammatory markers, fecal calprotectin, and colonoscopy with biopsies if clinical suspicion exists 5, 4
• Celiac disease: Screen with serology in all patients with chronic abdominal pain 6, 4
• Microscopic colitis: Consider in middle-aged patients with chronic diarrhea, requires colonoscopy with random biopsies 6
• Small intestinal bacterial overgrowth (SIBO): May cause persistent symptoms in IBD patients but also implicated in functional disorders 5
• Bile acid diarrhea: Consider in patients with chronic diarrhea, particularly post-cholecystectomy 5

Distinguishing CAPS from Other Functional Disorders

CAPS versus IBS

• Pain pattern: IBS requires recurrent abdominal pain at least 1 day per week (not continuous), associated with changes in stool frequency or form, with pain often relieved by defecation 5, 4
• Bowel habit relationship: IBS pain correlates with altered bowel movements (looser stools with pain onset, more frequent stools with pain), whereas CAPS pain is independent of bowel function 5, 2
• Predominant feature: IBS is defined by disturbed bowel habit as primary feature, while CAPS is defined by constant pain with minimal gut dysfunction 5, 2

CAPS versus Functional Dyspepsia

• Pain location: Functional dyspepsia centers on epigastric pain or discomfort, while CAPS can involve any abdominal region 5
• Meal relationship: Functional dyspepsia symptoms relate to eating (postprandial fullness, early satiety), whereas CAPS pain is not exclusively related to meals 2

Overlap Syndromes

• Many CAPS patients have coexisting functional GI disorders: The presence of IBS, functional dyspepsia, or other functional conditions does not exclude CAPS if constant pain is the predominant feature 5, 3
• Polysymptomatic presentation: Multiple functional GI diagnoses plus extraintestinal symptoms (fibromyalgia, chronic fatigue, urinary frequency) indicate somatization and central amplification of visceral signals 1, 4

Critical Diagnostic Pitfalls

Narcotic Bowel Syndrome Recognition

• Opioid-induced GI hyperalgesia: Paradoxical development or worsening of abdominal pain with continuous or increasing opioid dosages characterizes narcotic bowel syndrome, with relief only occurring upon opioid withdrawal 2
• 66.7% of CAPS patients requiring frequent hospitalization are prescribed regular opiate analgesics, creating risk for narcotic bowel syndrome 3
• Opioid use in IBD patients with functional symptoms: In IBD patients with coexisting "IBS" diagnosis, narcotic use is significantly higher (17% in Crohn's disease versus 11% without IBS diagnosis), indicating inappropriate opioid prescribing for functional symptoms 5

Avoiding Iatrogenic Harm

• Unnecessary surgery: Patients with severe or refractory functional GI disorders and overlapping conditions are at high risk for inappropriate surgery that will not resolve centrally mediated pain and may worsen symptoms through additional surgical trauma and opioid exposure 1
• Misattribution to gallstones: Pain unrelated to eating argues strongly against biliary colic, and normal HIDA scan with normal ejection fraction definitively excludes functional gallbladder disorder—cholecystectomy in this setting causes iatrogenic harm 1
• Reinforcing illness behavior: Repetitive testing after negative initial workup reinforces patient conviction of undiagnosed organic disease and perpetuates healthcare-seeking behavior 5, 7

Psychosocial Assessment

Psychiatric Comorbidity Screening

• Depression: Present in 88.9% of CAPS patients with frequent hospitalizations, requiring formal screening with validated instruments 3
• Anxiety and panic disorders: Present in 38.9% of severe CAPS cases 3
• Post-traumatic stress disorder: Present in 27.8% of severe CAPS cases, often related to childhood or adult abuse history 5, 3
• Somatization: Multiple somatic complaints across organ systems indicate central amplification mechanisms 5, 1

Social and Occupational Factors

• Employment status: Only 27.8% of CAPS patients requiring frequent hospitalization are employed, often in healthcare professions 3
• Social stressors: Present in 33.3% of severe CAPS cases, including relationship problems, financial stress, or housing instability 3
• Consulting behavior: Approximately 50% of IBS patients attribute symptom onset to stressful events, and those who consult doctors report more severe symptoms and increased psychological disturbance compared to non-consulters 5

Establishing the Diagnosis

Positive Diagnosis Strategy

• Make a positive diagnosis based on typical symptoms rather than exhaustive testing: The working diagnosis can be safely made on the basis of typical symptoms, normal physical examination, absence of alarm features, and negative basic laboratory screening 5, 4, 7
• Confirm diagnosis through observation over time: In primary care, confirm the functional diagnosis by observing symptom pattern stability without development of alarm features 5
• Explain diagnosis using gut-brain axis framework: Establish that pain is real and multifactorial, involving central amplification mechanisms where the brain's pain processing system requires treatment, not that pain is "all in their head" in a dismissive sense 1

Documentation Requirements

• Duration: Document that pain has been present continuously or nearly continuously for at least 6 months 2
• Functional impact: Document specific ways pain interferes with work, social activities, and daily functioning 1, 2
• Relationship to physiological events: Document that pain is not exclusively related to eating, defecation, or menses 2
• Negative workup: Document that structural and biochemical abnormalities have been excluded through appropriate testing 2
• Central features: Document presence of closed eyes sign, catastrophizing, hypervigilance, or other behavioral indicators of central sensitization 1