Defining the sites and mechanisms of nociception is an important step in understanding and treating pain. During inflammation, increased nociceptive input from an inflamed organ can sensitize neurons that receive convergent input from an unaffected organ, but the site of visceral cross-sensitivity is unknown. This study examined the cellular responses to ATP and substance P stimulation in sensory neurons innervating visceral organs.Lumbosacral dorsal root ganglia (L6-S1) were cut into slices and processed for substance P receptor expression using immunocytochemistry. Primary culture of dorsal root ganglion (DRG) neurons was used for [Ca2+]i measurement by videomicroscopy.DRG neurons express substance P receptors. Both brief addition of low dose adenosine triphosphate (ATP, 5 microM) and substance P (10 microM) significantly increased subsequent ATP stimulation at the same neuron.Sensitization of the DRG neurons innervating the different organs may be through the release of nociceptive transmitters such as ATP and/or substance P within the ganglion. Together, these experiments will increase our understanding of the important modulatory role of peripheral sensitization in nociceptive transmission and suggest potential periphepheral sites for therapeutic intervention.