Chronic visceral pain is a complex and often a serious burden on patients’ life. It is strongly implicated in the etiology of many diseases, which often are complicated by co-morbid depression and other psychiatric disorders, all of which pose significant health risks. Understanding the mechanisms of nociception is an important step in treating pain-associated chronic diseases. The inflammatory process that is often associated with nociception produces a number of mediators, which activate nociceptors by interacting with ligand-gated ion channels, activation of different signal transduction pathways or by sensitizing primary afferent neurons located within the dorsal root ganglia (DRG). Primary afferents studied in vitro or in vivo are well-accepted models to examine various nociceptive and anti-nociceptive signals in peripheral nervous system. This review focuses on the recent work in the area of peripheral modulation of chronic pain at the level of visceral primary afferent neurons. Many studies intended to develop a coherent framework for a better understanding of heterogeneity of nociceptive neurons functioning as a gate for pain transmission and novel therapeutic tool for pain relief. Specifically, recent studies from the author’s research group helped to define the role of ATP-sensitive purinergic and vanilloid-sensitive TRPV1 receptors in DRG-mediated nociceptive pathways. Tropic and physiological changes associated with chronic visceral pain indeed are mediated through different pathways; therefore, designing new and specific anti-nociceptive therapies will have a major impact on quality of life in patients by significantly reducing pharmacological and therapeutic interventions.