The study of visceral pain is of high clinical relevance and the findings more directly translational in the search for analgesic agents. Early studies of nerve recordings after acute visceral nerve activation with (1) mechanical distension of hollow organs such as the colon or esophagus, (2) chemical irritation, and/or (3) inflammation have provided relevant information about normal, typically silent visceral afferents and evoked behavioral responses. Clinically relevant information about visceral pain has been reported in studies utilizing intact animal models of inflammatory, diabetic, neuropathic, cancer, chemotherapy-induced and other injury-related visceral pain conditions. More recently, animal models designed to study mechanisms signaling the transitional stages from acute to chronic visceral pain are providing information relevant to the development of drug therapies for reducing visceral pain in patients with these conditions. As an example, a visceral pain model of chronic pancreatitis is induced with an alcohol and high-fat diet in rat that persists for 2 months. Increased sensitization, inflammation, and pancreatic tissue disruption typical in the model are reversed by overexpression of met-enkephalin by a herpes simplex viral (HSV) preproenkephalin vector. The therapeutic effects are most likely attributable to opioid receptors located both in the central and peripheral nervous systems, as well as on peripheral cells. Advantages of using (HSV) vectors for therapeutic gene delivery rather than other viral delivery vectors (lentivirus, adenovirus) in certain clinical settings to treat visceral pain are discussed.