Role of voltage-dependent calcium channel subtypes in spinal long-term potentiation of C-fiber-evoked field potentials

Activity-dependent increases in the responsiveness of spinal neurons to their normal afferent input, termed central sensitization, have been suggested to play a key role in abnormal pain sensation. We investigated the role of distinct voltage-dependent calcium channel (VDCC) subtypes in the long-term potentiation (LTP) of C-fiber-evoked field potentials (FPs) recorded in the spinal dorsal horn of rats, that is, a synaptic model to describe central sensitization. When spinally applied, we observed that omega-conotoxin GVIA (omega-CgTx), an N-type VDCC antagonist, produced a dose-dependent and prolonged inhibition of basal C-fiber-evoked FPs in naive animals. omega-CgTx did not perturb the induction of LTP by high-frequency stimulation (HFS) of the sciatic nerve; however, potentiation was maintained at a lower level. Following the establishment of spinal LTP in naive animals, the inhibitory effect of omega-CgTx on C-fiber-evoked FPs was significantly increased. Furthermore, in animals with chronic pain produced via peripheral nerve injury, where spinal LTP was barely induced by HFS, basal C-fiber-evoked FPs were strongly inhibited by omega-CgTx. As a result, omega-CgTx exerted a similar inhibitory profile on C-fiber-evoked FPs following the establishment of spinal LTP and chronic pain. In contrast, spinally administered omega-agatoxin IVA (omega-Aga-IVA), a P/Q-type VDCC antagonist, showed little effect on C-fiber-evoked FPs either before or after the establishment of LTP, but strongly suppressed LTP induction. These results demonstrate the requirement of N- and P/Q-type VDCCs in the maintenance and induction of LTP in the spinal dorsal horn, respectively, and their distinct contribution to nociceptive synaptic transmission and its plasticity. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.