1. Long-lasting increases in synaptic efficacy following repetitive stimulation have been demonstrated at several sites in the CNS, where they are collectively termed long-term potentiation (LTP). LTP is of interest with respect to its presumptive relationship to learning and memory in hippocampus. In the spinal cord in vivo, an LTP-Like phenomenon is thought to underlie the allodynia and hyperalgesia that follows some peripheral injuries. 2. We investigated the capacity of the isolated neonatal rat spinal cord to sustain a long-lasting increase in a nociceptive-related slow ventral root potential (sVRP) recorded from a lumbar root after a tetanic train of stimuli to the peripheral cutaneous saphenous nerve. Stimuli were delivered at a low constant (0.02 s(-1)) frequency during a 30-min control period. A tetanic stimulus train (10 s(-1) for 60 s) was then given followed by a resumption of low (0.02 s(-1)) frequency stimulation. Potentiation was defined as an increase in sVRP area >2 SD above control mean. 3. Twenty of 20 preparations showed immediate posttetanic potentiation. In 13 of the 20, potentiation was maintained for greater than or equal to 1 h after the tetanic stimulus train. 4. Potentiation was dependent on activation of C fibers during the inducing train; stimuli below C-fiber threshold, activating only A fibers, were ineffective. Potentiation was selectively expressed by a long-latency component of the sVRP elicited by stimuli at a strength that evoked both A-and C-fiber responses in the nerve. Shorter duration components elicited by A-fiber strength stimuli and sensitive to the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) did not potentiate. 5. The N-methyl-D-aspartate (NMDA) receptor antagonist (DL)-AP-5 reduced sVRP area by as much as 65%; 80 mu M was the maximally effective concentration. When AP-5 (80 mu M) was applied during the inducing train and then washed out, seven of eight preparations displayed LTP. The magnitude of potentiation (147.5 +/- 37.71% of control, mean +/- SD) was not different from that observed in untreated preparations. The region of the sVRP maximally depressed by AP-5 showed only transient potentiation after the tetanus. All the LTP of the total area was contributed by longer-latency components. 6. The selective tachykinin receptor antagonists RP 67,580 (NK1) and MEN 10,376 (NK2) each reduced sVRP area to similar to 85% of control. Neither antagonist prevented LTP when applied during the inducing train. 7. The present results demonstrate and characterize in preliminary fashion a form of LTP in spinal cord. The LTP is dependent on C-fiber input both for induction and expression. It is apparently not dependent on NMDA receptors for induction or expression, or on tachykinin NK1 and NK2 receptors for induction. Calcium influx through voltage-dependent calcium channels is suggested as a possible mechanism for induction.
