Long-term potentiation (LTP) of C-fiber evoked field potentials in spinal dorsal horn may be relevant to pathological pain. Our previous work has demonstrated that the late phase of the spinal LTP is protein synthesis-dependent. Considerable evidence has accumulated that dopamine D1/D5 receptors are important for late phase LTP in hippocampus. In the present work the role of D1/D5 receptors in LTP of C-fiber evoked field potentials in spinal dorsal horn was evaluated in Urethane anesthetized Sprague-Dawley rats. We found (1) Spinal application of SKF 38393, a D1/D5 receptor agonist induced a slowly developed LTP of C-fiber evoked field potentials, lasting for more than 10 h and the effect was blocked by the D1/D5 antagonist SCH 23390, while a D2 receptor agonist (Quinpirole) induced depression of C-fiber responses, lasting for 2h. (2) The potentiation produced by D1/D5 receptor agonist occluded the late phase but not the early phase of the spinal LTP produced by tetanic stimulation. (3) SCH 23390 selectively depressed the late phase LTP, when applied 40 min prior to tetanic stimulation. (4) The D1/D5 agonist-induced potentiation is blocked by the protein synthesis inhibitor anisomycin. (5) Activation of PKA by spinal application of 8-Br-cAMP also induced the spinal LTP and the action occluded the potentiation induced by D1/D5 receptor agonist. These results suggest that the spinal D1/D5 receptors participate in the protein synthesis-dependent late phase LTP of C-fiber evoked field potentials in spinal dorsal horn via cAMP signaling pathway.