Visceral and somatic hypersensitivity as evidence of central sensory sensitization occur in the majority of Irritable Bowel Syndrome (IBS) patients. We recently demonstrated abnormal endogenous pain modulation as a cause of the sensitization in IBS and identified the underlying dysfunctional neuromatrix using functional MR-imaging (fMRI). Endogenous pain mechanisms regulate, fine-tune and integrate sensory and homeostatic, including neuroendocrine, immune and autonomic nervous system processes. Specific measures of sensitization and endogenous pain modulation correlate with clinical measures of somatic and neuropathic pain, suggesting usefulness as surrogate markers for clinical pain outcomes. Validation of experimental measures as surrogate markers in IBS would provide a considerable advance in pathophysiological and therapeutic research in this pharmacoeconomically burdensome disease.

Inclusion Criteria:

IBS patients:

• One hundred fifty male and female IBS patients (Rome III criteria), aged 18 to 70 years, recruited from primary and secondary care via advertisements and referral networks.
• Minimum IBS symptom rating of 75 in IBS severity scoring system (IBS-SSS) in last two weeks.
• IBS discomfort or pain must have been patient's most prominent symptom.
• A minimum of 40 patients each IBS-constipated (IBS-C) and IBS-diarrhoeic (IBS-D) (Rome III) to be included.
• Patients must have been off all IBS and analgesic medication and any drugs potentially influencing sensory function for at least two weeks before study start.

Healthy controls:

• Fifteen healthy controls aged 18 to 70 years without any gastrointestinal pathology or history of significant abdominal pain, bowel disorders, bloating or discomfort during the last 3 months.

Exclusion Criteria:

Exclusion criteria for both IBS patients and healthy controls:

• Organic gastrointestinal or other significant systemic disease, including cardiovascular, psychiatric, neurological and endocrine diseases, as judged by investigator
• Chronic or acute pain, except related to other functional syndromes (functional dyspepsia, chronic pelvic pain, fibromyalgia, migrane)
• Bowel resections (except appendectomy)
• Multiple abdominal operations, excluding hysterectomy
• History of brain disease or brain surgery
• Ongoing treatment with any anticoagulants, antidiabetics, antimigraine drugs, antispasmodics, analgesics, psychoactive agents including antidepressants, Zelmac®, TCM or acupuncture for IBS and any drugs affecting nociception as judged by investigator within last 14 days
• Treatment with any investigational drug during the preceding 30 days
• Pregnancy or lactation.
• Claustrophobia
• Metal implants in body (fMRI exclusion criterion)
• No written informed consent obtained from subject