Understanding the signaling and transmission of visceral nociceptive events

Visceral pain can be considered as part of the defense reactions of the body against harmful stimuli, particularly of those that impinge on the mucosal lining of hollow organs. It is a problem of considerable clinical relevance, and its neurobiological mechanisms differ from those of somatic nociceptive or neuropathic pain. Much progress had been made in recent years in the understanding of the functional properties of the visceral nociceptors that trigger pain states, their molecular mechanisms of activation and sensitization and on their central actions. Some molecular targets have been identified as key players in the activation and sensitization of visceral nociceptors, notably ASICs, TTX-resistant Na channels and the TRPV1 receptor. Some nonneural elements of visceral organs, such as the urothelium have been shown to play active roles in the transduction of visceral sensory events by mechanisms involving ATP release by the urothelial cells. Certain well-known neurotransmitters, such as the tachykinin family of neuropeptides, likely play an important role in the peripheral and central activation of visceral nociceptive afferents and in the generation of visceral hyperalgesia. This article reviews current evidence on the mechanisms of activation and sensitization of visceral nociceptive afferents and on their role in the triggering and maintenance of clinically relevant visceral pain states.