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Ness, T. J., and G. F. Gebhart. Inflammation enhances reflex and spinal neuron responses to noxious visceral stimulation in rats. Am J Physiol Gastrointest Liver Physiol 280: G649-G657, 2001.--To improve understanding of sensory processes related to visceral inflammation, the effect of turpentine-induced inflammation on reflex (cardiovascular/visceromotor) and extracellularly recorded lumbosacral dorsal horn neuron responses to colorectal distension (CRD) was investigated. A 25% solution of turpentine, applied to the colorectal mucosa, produced inflammation, decreased compliance of the colonic wall, and enhanced reflex responses in unanesthetized rats within 2-6 h. At 24 h posttreatment, pressor responses to CRD (80 mmHg, 20 s) were 20% greater, and intraluminal pressures needed to evoke visceromotor reflexes were 30% lower than controls. Parallel electrophysiological experiments in spinal cord-transected, decerebrate rats demonstrated that two neuronal subgroups excited by CRD were differentially affected by turpentine administered 24 h before testing. During CRD, abrupt neurons were 70% less active and sustained neurons were 25% more active than similar neurons in controls. In summary, reflex and neuronal subgroup (sustained neurons) responses to CRD were both potentiated by chemical inflammation. This suggests that the neurophysiological basis for inflammation-induced increases in reflex responses to CRD is increased activity of this neuronal subgroup. colorectal; nociception; turpentine; visceral hyperalgesia

Gebhart, G. F. Pathobiology of Visceral Pain: Molecular Mechanisms and Therapeutic Implications. IV. Visceral afferent contributions to the pathobiology of visceral pain. Am J Physiol Gastrointest Liver Physiol 278: G834-G838, 2000. --Functional bowel and other visceral disorders exhibit multiple characteristics that suggest the presence of visceral hyperalgesia. The discomfort, pain, and altered sensations (e.g., to intraluminal contents) that define the hyperalgesia typically arise in the absence of tissue insult or inflammation. Visceral hyperalgesia thus differs from somatic hyperalgesia, which is commonly associated with tissue injury and inflammation. Hyperalgesia could develop and be maintained by either peripheral or central mechanisms; the altered sensations associated with functional visceral disorders are contributed to by both peripheral and central mechanisms. The relative contributions of peripheral and central mechanisms are not well understood, and the focus in this Themes article is on potential peripheral contributions: sensitization of visceral receptors, nerve injury, and ion channels. ion channels; mechanosensitive; polymodal; visceral hyperalgesia

Su, Xin, Ruth E. Wachtel, and G. F. Gebhart. Capsaicin sensitivity and voltage-gated sodium currents in colon sensory neurons from rat dorsal root ganglia. Am. J. Physiol. 277 (Gastrointest. Liver Physiol. 40): G1180-G1188, 1999.--DiI-labeled colon sensory neurons were acutely dissociated from S1 rat dorsal root ganglia (DRG) and studied using perforated whole cell patch-clamp techniques. Forty-six percent (54/116) of labeled sensory neurons responded to capsaicin ([10.sup.-8]-[10.sup.-5] M) with an increase in inward current, which was a nonspecific cation conductance. Responses to capsaicin applied by puffer ejection were dependent on dose, with a half-maximal response at 4.9 x [10.sup.-7] M; bath application was characterized by marked desensitization. Voltage-gated [Na.sup.+] currents in 23 of 30 DRG cells exhibited both TTX-sensitive and TTX-resistant components. In these cells, capsaicin induced an inward current in 11 of 17 cells tested. Of the cells containing only a TTX-sensitive component, none of six cells tested was sensitive to capsaicin. In all cells that responded to capsaicin with an increase in inward current, capsaicin abolished voltage-gated [Na.sup.+] currents (n = 21). Capsazepine ([10.sup.-6] M) significantly attenuated both the increase in inward current and the reduction in [Na.sup.+] currents. [Na.sup.+] currents were not significantly altered by adenosine, bradykinin, histamine, [PGE.sub.2], or serotonin at [10.sup.-6] M and [10.sup.-5] M. These findings may have important implications for understanding both the irritant and analgesic properties of capsaicin. visceral pain; bradykinin; prostaglandin [E.sub.2]; serotonin; tetrodotoxin