The current treatment of visceral pain associated, for instance, with functional bowel disorders (FBDs) such as functional dyspepsia and irritable bowel syndrome (IBS) is unsatisfactory. Therapeutic advances are badly needed in view of the high prevalence of chronic or recurrent visceral pain and its socioeconomic burden as outlined in Chapters I/1 and I/2. This gap in the pharmacologic management of visceral pain reflects the incomplete understanding of the underlying mechanisms, which lags behind the knowledge of somatic pain mechanisms. In addition, the utility of nonsteroidal anti-inflammatory drugs and opiates, which are the mainstay in somatic pain management, is limited by their severe adverse effects on gastrointestinal (GI) mucosal homeostasis and motility, respectively. Although progress in the use of opioid and nonopioid drugs for the treatment of abdominal pain is being made (see Chapters III/18 and III/19), there is clearly a need to identify new targets for visceral pain therapy.
There are multiple mechanisms that contribute to the initiation and maintenance of FBDs at the level of the GI tract, the afferent nervous system and the brain. Novel therapies of FBDs may therefore be targeted (i) at the derangements of digestive functions, (ii) the hyper-sensitivity of afferent neurons, (iii) the exaggerated processing of afferent information in the brain in the context of a variety of psychosocial factors (gut-brain axis), and (iv) the disturbed control of GI functions by the brain through the autonomic nervous system and endocrine mechanisms (brain-gut axis). Besides neurophysiologic, psychologic, complementary, and integrative treatment strategies (see other chapters of this volume), medicines addressing hypersensitive afferent neurons represent a potentially important strategy (Table 1). In addition, drugs that help normalize the disturbances in GI function seen in FBDs may indirectly reduce visceral pain. This article focuses on sensory neuron-specific receptors (SNSR), ion channels, and messenger molecules that have potential in the therapy of visceral hyperalgesia.
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