There is no specific diagnostic finding or biomarker for IBS, so the diagnosis is based on patients’ reports of their symptoms. In the past, IBS was considered a diagnosis of exclusion, but inherent to this approach is an exhaustive diagnostic work-up that involves unpleasant and potentially risky tests for the patient and is not cost effective. Thus, a symptom-based diagnostic system, known as the Rome criteria, was developed. The main concept introduced by the Rome criteria is that the diagnostic process of a functional disorder should be based on two components. The first is the presence of a typical cluster of symptoms and the second is the absence of “red flags” including initial presentation of symptoms at an age over 50, unexplained weight loss, fever, nocturnal symptoms, blood in the stool, a family history of gastrointestinal malignancy or disease (e.g., celiac or inflammatory bowel disease), or an abnormal finding on physical examination. Basic laboratory tests, such as a complete blood count and celiac serology, are usually enough to complete the diagnostic process and establish a firm diagnosis. Patients who fulfill the criteria and do not have red flags need a minimal diagnostic work-up after which the diagnosis of IBS can be made with confidence [16, 17].

The latest update of the Rome diagnostic criteria for IBS is Rome III, in which the diagnosis of IBS requires the presence of abdominal pain or discomfort for at least 10 % of the time over the previous three months with symptom onset at least six months earlier [18]. Additionally, pain should be relieved by defecation and associated with a change in the frequency of bowel movements or a change in the form of the stool. Accompanying symptoms, although not essential for the diagnosis, are a feeling of incomplete evacuation, abnormal stool frequency (less than three times a week or more than three times a day) or consistency, straining at defecation, urgency, mucus discharge, and bloating. IBS can be further divided into three main subgroups according to bowel habit as constipation predominant (IBS-C), diarrhea predominant (IBS-D), and those exhibiting an alternating bowel pattern [19]. Patients may switch from one subclass to another during the course of their illness. It has been demonstrated repeatedly that the use of positive symptom-based diagnostic criteria in conjunction with the use of red flags to guide further investigation in selected cases is a reliable and cost-effective approach. After establishing the diagnosis of IBS, based on the Rome criteria, it is rarely necessary to change the diagnosis [20–22].

Abdominal pain is a hallmark of IBS and is essential for its diagnosis. In IBS, as in many other chronic pain syndromes, pain is a complex experience resulting from the interplay between peripheral (visceral) stimulation (enteric nervous system) and central modulation (central nervous system [CNS]).

Afferent stimulation from the colon is transmitted to second-order neurons in the spinal cord and then ascends to the brain through the spinothalamic, spinoreticular, and spinomesencephalic tracts. These tracts connect to the somatosensory cortex responsible for registration and localization of painful visceral and somatic stimuli. They also connect to structures in the limbic system that are involved in the reflexive, affective, and motivational responses to pain [23]. The afferent pathways project to the perigenual anterior cingulate cortex (pACC), which is involved in affective modification, and to the midcingulate cortex (MCC), which is involved in the behavioral response.

The amplification of afferent visceral stimulation can result from increased excitability of peripheral receptors or impaired spinal and/or central pain regulatory systems. Increased excitability can produce the two related phenomena of hyperalgesia (increased pain response to painful stimuli) and allodynia (increased pain response to nonpainful stimuli) [24]. Thus, afferent visceral stimulation can be experienced as painful not only as a result of peripheral intensity but also as a result of central processing that may be modulated by psychosocial factors such as anxiety, depression, poor social support, and impaired coping skills [25]. As the severity of pain increases central processing plays an increasingly important role compared to peripheral input. Once a pattern of central sensitization has taken hold, patients may even experience severe pain without ongoing peripheral nociceptive stimulation [26, 27]. This is the extreme end of the IBS severity spectrum.

While we do not have full knowledge of all the causes of excessive peripheral stimulation, there is good evidence that eating, infection, inflammation, physical injury, hormones (e.g., menses), or colonic motility may play a role.

Up to 15 % of IBS patients attribute the beginning of their symptoms to an acute episode of gastrointestinal infection. A meta-analysis of eight papers including almost 600,000 patients over a follow-up up to one year found that the odds ratio for developing IBS after such an episode is seven [28]. IBS that follows acute intestinal infection has been shown to be associated with a persistent or chronic state of inflammation that cannot be identified by routine clinical tests and procedures [29, 30].

Risk factors for postinfectious IBS are related to not only to the severity of the acute infectious episode (fever, bloody stools, and need for hospitalization) but also to patient characteristics such as female gender, stress, anxiety, and depression [31]. This is a good example of how excessive afferent stimulation, induced in this case by a microinflammatory state, can develop into a chronic condition such as IBS-D after central sensitization occurs in a susceptible person with psychological comorbidity.

Peripheral stimulation and its interplay with central amplification are also reflected in the development of chronic abdominal pain following abdominal or pelvic surgery. IBS patients reported up to twice the number of appendectomies and hysterectomies and up to three times the number of cholecystectomies compared with those without IBS [32]. Surgery may cause visceral afferent sensitization that eventually results in allodynia and chronic pain even in the presence of normal gut function.

This contention is supported by a study that evaluated the development of abdominal pain after elective gynecologic surgery for nonpainful indications [32]. Patients with no prior history of chronic abdominal pain undergoing gynecological surgery for nonpainful indications were followed for the development of de novo abdominal pain following surgery. They were compared with a control group comprised of nonsurgical patients who came to a gynecologic clinic for nonpain-related reasons. At one-year follow-up significantly more patients in the surgery group complained of chronic abdominal pain (15.3 %) than in the control group (3.6 %, p = 0.003). There was no association between any surgery-related variables and the subsequent development of chronic abdominal pain. The only predictors of chronic abdominal pain at one-year follow-up were associated with the patients’ preoperative psychological profile. Patients anticipating difficulty with surgery or recovery from it and those with lower scores on the Sense of Coherence questionnaire (an index of coping skills) were more likely to develop chronic postoperative abdominal pain. In these cases, the interplay of peripheral visceral stimulus together with central sensitization related to psychosocial variables affected the de novo development of chronic abdominal pain.

Studies using functional MRI and PET CT have demonstrated that the ACC, which is responsible for descending pain inhibition, is less active in IBS patients. This phenomenon is also found in other chronic pain syndromes such as fibromyalgia [33–35]. In contrast, the MCC, which is associated with unpleasantness and fear, is overactive. Therefore, in IBS patients the normal adaptive inhibitory response to painful visceral stimuli is diminished and replaced by a maladaptive, presumably even aggravating, response [33, 34, 36]. The factors that ultimately lead to this shift into a maladaptive pattern are psychosocial in nature. This connection was elegantly demonstrated in the case report of a patient with a severe functional gastrointestinal pain syndrome and a history of abuse [37]. Her baseline brain scan demonstrated marked activation of the MCC and the somatosensory cortex. Following successful treatment with antidepressants and psychotherapy a repeated scan demonstrated diminished MCC activity and increased insular activation. Thus, maladaptive brain responses are reversible and so is the patient’s clinical situation.

As in other fields of medicine, in particular in patients with chronic painful conditions, the healing process for IBS patients begins when the patient enters the doctor’s office before any medicine has been prescribed. It is of the outmost importance to establish a good doctor–patient relationship in order to succeed in the therapeutic process [38, 39]. Some of the essentials of a salutary doctor–patient relationship are discussed below:

Many IBS patients have never received a comprehensive explanation about the nature of their problem. This may be the basis for the unwarranted fears (“I might have cancer”) and feelings of frustration (“why can’t they figure out what I have”). A detailed explanation about the nature of functional disorders and their natural history is very important to deal with these issues.

Treating IBS patients is an ongoing process that takes time. Throughout this process patients are likely to encounter difficulties, setbacks, and frustration. Patients should not feel that they are left alone to deal with their setbacks. Scheduling a follow-up phone call, for example, is a simple measure that is often sufficient to allay patients’ new concerns [41]. Physicians should inquire about comorbid gastrointestinal and nongastrointestinal functional disorders. IBS patients have a high prevalence of other functional disorders [42], leading some patients to feel that they are very ill. By providing patients with a unifying paradigm that connects different, apparently unrelated, symptoms to one disorder (i.e., central sensitization), we can alleviate much of their fears and concerns.

For some patients with mild symptoms, these steps may be enough to alleviate fears and concerns regarding their symptoms. These patients often continue to cope successfully with their symptoms and need no further treatment. However, the majority of patients will require more specific treatment.

The treatment options for IBS can be divided into pharmacological and nonpharmacological treatment modalities (Fig. 6.1).