The induction of long-term potentiation in spinal dorsal horn after peripheral nociceptive stimulation and contribution of spinal TRPV1 in rats.

During chronic pain states, peripheral nociceptive stimulation can induce long-term potentiation (LTP) in the spinal dorsal horn, but it is not clear how quickly spinal LTP develops after peripheral noxious stimulation. Furthermore, transient receptor potential vanilloid type 1 (TRPV1) receptors are abundant in spinal cord dorsal horn, especially in the superficial layers, and are thought to be involved in synaptic plasticity. In this study, we investigated the time frame of LTP induction after inflammatory insult and electrical stimulation and the involvement of TRPV1 receptors. By using extracellular recordings of C-fiber-evoked field potentials in the superficial spinal dorsal horn and teased fiber recording in vivo, we found that subcutaneous injection of complete Freund's adjuvant (CFA) or 5% formalin induced low-frequency, irregular discharges of C-fibers and LTP of the C-fiber-evoked field potentials in the spinal dorsal horn within 3h. Topical application of the TRPV1 receptor antagonist capsazepine onto the spinal cord inhibited the induction of spinal LTP by CFA or formalin. Furthermore, capsazepine and another TRPV1 antagonist, (E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide, partially or completely blocked the LTP induced by conditioning stimulation with high- and low-frequency electrical stimulation. These results suggest that acute peripheral inflammatory stimulation by CFA or 5% formalin can induce spinal LTP very early after stimulation onset and that TRPV1 receptors in the spinal dorsal horn might contribute to this LTP induction.