This study was designed to test the hypotheses that pain syndromes associated with specific body regions reflect unique properties of sensory neurons innervating these regions and/or unique responses of these afferents to tissue damage. Acutely dissociated adult rat dorsal root ganglia (DRG) neurons retrogradely labeled from either the colon or the glabrous skin of the hindpaw were studied by whole cell patch-clamp recording in current-clamp mode. Two populations of colonic afferent neurons were studied: pelvic afferents (arising from L₆, S₁, and S₂ DRG = LS DRG) and hypogastric/lumbar colonic afferents (arising from T₁₃, L₁, and L₂ DRG = TL DRG). Passive and active electrophysiological properties were studied before and after application prostaglandin E₂ (PGE₂). We observed marked differences between cutaneous and colonic sensory neurons with respect to baseline passive and active electrophysiological properties as well as both the magnitude and pattern of PGE₂-induced changes in excitability, passive, and active properties. There were also significant differences between TL and LS neurons with respect to baseline and PGE₂-induced changes in several passive and active electrophysiological properties. Our results suggest that differences between cutaneous and colonic neurons reflect differences in pattern and/or density of ionic currents present in the plasma membrane. More interestingly, the ionic currents underlying the PGE₂-induced sensitization of cutaneous neurons appeared to differ from those underlying the sensitization of colonic neurons. The implication of this observation is that it may be possible, in fact necessary, to treat pain arising from specific body regions with unique therapeutic interventions.