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Increased sensitivity of visceral nociceptive pathways contributes to symptoms in an array of clinical gastrointestinal conditions, however, the search for a consistently effective pharmacological agent to treat these conditions remain elusive. Modulation of visceral nociceptive pathways can occur at peripheral, spinal and supra-spinal sites and a dizzying array of potential drug targets exists. Till date, only tricyclic anti-depressants (TCAs) such as amitriptyline and, more recently, selective serotonin reuptake inhibitors (SSRIs) such as citalopram have demonstrated convincing visceral anti-nociceptive properties and clinical benefit in a limited population of patients with visceral hypersensitivity. Unfortunately, there is an incomplete understanding of the receptors and/or primary site of action at which these compounds exert their effects and significant side effects are often encountered. There is a continuing and concerted effort underway to develop target-specific visceral analgesic/anti-hyperalgesic compounds and the aim of this article is to provide a concise update on the most recent advances in this area.