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Chronic constipation is a frequent pathological condition bearing relevant socioeconomic burdens, mainly due to uncertain management and unsatisfactory response to traditional laxatives. Prucalopride is a novel enterokinetic drug, that has been demonstrated to improve bowel functions and relieve a broad spectrum of digestive symptoms in patients with severe chronic constipation who had failed to respond to various traditional laxatives. In this paper we discussed the practical aspects of chronic constipation treatment, in particular focusing on some questions about the practical use of prucalopride. Prucalopride is a potent, selective, high-affinity agonist of the 5-HT4 receptors widely expressed in the gastrointestinal tract. Unlike other 5-HT4 agonists, such as cisapride and tegaserod, it is devoid of adverse cardiovascular effects. Furthermore, it is characterized by a low potential for interactions with other drugs, due to its pharmacokinetic characteristics. Prucalopride was approved, in 2009, by the European Medicines Agency for the symptomatic treatment of chronic constipation in women in whom laxatives fail to provide adequate relief, however, there are ongoing studies to extend the use of the drug even to males.

Chronic constipation is a common condition in the general population. Although the majority of affected individuals do not seek medical consultation and search for remedies for their condition in the pharmacy or herbal shops, the actual health burden caused by this condition is extremely high. Many laxatives are available, but patients are often dissatisfied with the therapies adopted, whether prescribed by a doctor or self prescribed, and this leads to further social and health burdens. All of the available guidelines promote initiating the therapy of any type of constipation by ensuring an adequate intake of dietary fiber and water. However, high amounts of insoluble vegetable fiber such as those normally contained in fruits and vegetables, can lead to a further worsening of the digestive symptoms typical of chronic constipation, such as bloating and distension and pain. Better results can be obtained with soluble fibers, such as psyllium. Among the various available laxatives, polyethylene glycol (PEG), or macrogol, is the product which has been most studied and has produced the best results with the least number of side effects. This is an inert not absorbable molecule that, diluted in water, forms an isotonic solution that prevents part of the water from being absorbed, thus increasing the volume of the intestinal contents, reducing the consistency and facilitating transport and evacuation. The combination of psyllium and PEG could combine the advantages of fiber and isotonic solutions and represent an important therapeutic option for patients suffering from chronic constipation.

The role of Helicobacter pylori and the accompanying mucosal inflammatory response in functional dyspepsia is still undefined. Human and animal studies have clearly demonstrated a link between intestinal mucosal inflammation and changes in sensory-motor function. Growing clinical and basic evidence supports the concept that a similar paradigm may occur in H. pylori-related dyspepsia. The infection may both induce gastric dysmotility and trigger neuroplastic changes in the afferent neural pathways leading to visceral hyperalgesia. A reduction of central antinociceptive control systems may also play a pathophysiological role. H. pylori eradication has provided disappointing results in terms of improvement of symptoms. This may reflect the long-term recovery of neuroplastic changes occurring in the afferent nervous system or, alternatively, the incomplete resolution of gastritis and the persistent production of inflammatory mediators by resident cells in the muscularis externa. The identification of these mechanisms may provide a better understanding of the pathophysiology of H. pylori-related dyspepsia and prompt innovative therapeutic approaches.

The innervation of the alimentary tract (or enteric nervous system, ENS) represents the third division of the autonomic nervous system and it appears to be unique for its intrinsic ability to mediate reflex activity even when disconnected from the central nervous system. Enteric nerve cells can be classified in subclasses according to combined classic morphological criteria (Dogiel type I, II and III) and electrophysiological properties (type S and AH). A further major feature of the ENS lies in the variety of chemical messengers expressed in its neuronal elements. These substances can act either as neurotransmitters or neuromodulators. A common finding of enteric neurons is to synthetize and store several chemical messengers, a phenomenon known as neurochemical coding. As a consequence, neurotransmission involves the release and action of more than one messenger, an event referred to as plurichemical transmission. Recently, the use of combination of methods (such as immunohistochemical, pharmacological and electrophysiological techniques) has led to the identification of specific functionally distinct categories of enteric neurons. Thus, inhibitory and excitatory motor neurons, interneurons, vasomotor and sensory neurons are now recognized to constitute the complex network of the ENS. These neuronal elements are synaptically connected to form microcircuits which play a pivotal role to control digestive functions, including motility, blood flow, secretion and absorbtion.