Direct activation of rat spinal dorsal horn neurons by prostaglandin E2

Whole-cell patch-clamp and intracellular recording techniques have been use d to study the action of prostaglandin E2 (PGE2) on neurons in adult rat tr ansverse spinal cord slices. Bath-applied PGE2 (1-20 muM) induced an inward current or membrane depolarization in the majority of deep dorsal horn neu rons (laminas III-VI; 83 of 139 cells), but only in a minority of lamina II neurons (6 of 53 cells). PGE2 alone never elicited spontaneous action pote ntials; however, it did convert subthreshold EPSPs to suprathreshold, leadi ng to action potential generation. PGE2-induced inward currents were unaffe cted by perfusion with either a Ca2+-free/high Mg2+ (5 mM) solution or tetr odotoxin (1 muM), indicating a direct postsynaptic action. Both 17-phenyl t rinor prostaglandin E2 (an EP1 agonist) and sulprostone (an EP3 agonist) ha d little effect on membrane current, whereas butaprost methyl ester (an EP2 agonist) mimicked the effect of PGE2. Depolarizing responses to PGE2 were associated with a decrease in input resistance, and the amplitude of inward current was decreased as the holding potential was depolarized. PGE2-induc ed inward currents were reduced by substitution of extracellular Na+ with N -methyl-D-glucamine and inhibited by flufenamic acid (50-200 muM), which is compatible with activation of a nonselective cation channel. These results suggest that PGE2, acting via an EP2-like receptor, directly depolarizes s pinal neurons. Moreover, these findings imply an involvement of spinal cord -generated prostanoids in modulating sensory processing through an alterati on in dorsal horn neuronal excitability.