LONG-TERM POTENTIATION IN AN ISOLATED PERIPHERAL NERVE-SPINAL CORD PREPARATION. Lozier, Alan P., Joan J. Kendig. Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, Telephone: 415-723-7442; FAX: 415-725-8052, EM: KENDIG@LELAND.STANFORD.EDU.
APStracts 2:0155N, 1995.
Summary and Conclusions 1. Long-lasting increases in synaptic efficacy following repetitive stimulation have been demonstrated at several sites in the central nervous system, 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 which follows some peripheral injuries. 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 following 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 more than 2 SD above control mean. 3. Twenty of 20 preparations showed immediate post-tetanic potentiation. In 13 of the 20, potentiation was maintained for an hour or more 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 which evoked both A- and C-fiber responses in the nerve. Shorter duration components elicited by A- fiber strength stimuli and sensitive to the AMPA/kainate antagonist CNQX did not potentiate. 5. The 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, 7 of 8 preparations displayed LTP. The magnitude of potentiation (68.85% +/- 15.35) was not different from that observed in untreated preparations. The region of the sVRP maximally depressed by AP-5 showed only transient potentiation following the tetanus. All the long-term potentiation 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 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 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. 

Received 3 February 1995; accepted in final form 4 April 1995.
APS Manuscript Number J74-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.