Effects of N- and L-type calcium channel antagonists on the responses of nociceptive spinal cord neurons to mechanical stimulation of the normal and the inflamed knee joint. V., Neugebauer,, Vanegas, H., Nebe, J., R[umlaut]umenapp, P., Schaible, H. G.. Physiologisches Institut, Universit[umlaut]at W[umlaut]urzburg, R[diaeresis]ontgenring 9, D-97070 W[umlaut]urzburg, Germany.
APStracts 3:0182N, 1996.
SUMMARY AND CONCLUSIONS
1) The present study addressed the involvement of voltage-dependent calcium channels of the N- and L-type in the spinal processing of innocuous and noxious input from the knee joint, both under normal conditions and under inflammatory conditions in which spinal cord neurons become hyperexcitable. In 30 anesthetized rats, extracellular recordings were performed from single dorsal horn neurons in segments 1-4 of the lumbar spinal cord. All neurons had receptive fields in the ipsilateral knee joint. In 22 rats, an inflammation was induced in the ipsilateral knee joint by kaolin and carrageenan 4-16 hours before the recordings. The antagonist at N-type calcium channels, _-conotoxin GVIA (_-CTx GVIA) was administered topically in solution to the dorsal surface of the spinal cord at the appropriate spinal segments in 6 rats with normal joints and in 12 rats with an inflamed knee joint. The antagonist at L-type channels, nimodipine, was administered topically in 5 rats with normal joints and in 11 rats with an inflamed knee joint. In another 5 rats with an inflamed joint, antagonists at L-type calcium channels (diltiazem and nimodipine) and _-CTx GVIA were administered ionophoretically with multibarrel electrodes close to the neurons recorded. 2) The topical administration of _-CTx GVIA to the spinal cord reduced the responses to both innocuous and noxious pressure applied to the knee joint in a sample of 11 neurons with input from the normal joint and in a sample of 16 neurons with input from the inflamed joint (hyperexcitable neurons). The responses were decreased to approximately 65% of the predrug values within administration times of 30 min. A similar reduction of the responses to innocuous and noxious pressure was observed when _-CTx GVIA was administered ionophoretically to 9 hyperexcitable neurons. In neurons with input from the normal or the inflamed knee joint, the administration of _-CTx GVIA led also to a reduction of the responses to innocuous and noxious pressure applied to the non-inflamed ankle joint. 3) The topical administration of nimodipine decreased the responses to innocuous and noxious pressure applied to the knee in a sample of 9 neurons with input from the normal joint and in a sample of 16 neurons with input from the inflamed knee joint (hyperexcitable neurons). Within administration times of 30 min, the responses were reduced to approximately 70% of the predrug values. In hyperexcitable neurons, the responses to innocuous and noxious pressure applied to the knee were also decreased during ionophoretic administration of nimodipine (6 neurons) and diltiazem (9 neurons). When the non-inflamed ankle was stimulated, the responses to innocuous pressure were neither reduced in neurons with input from the normal knee nor in neurons with input from the inflamed knee, but the responses of hyperexcitable neurons to noxious pressure onto the ankle were reduced. The ionophoretic administration of the agonist at the L-type calcium channel, S(-)-Bay K 8644 enhanced the responses to mechanical stimulation of the knee joint in all 14 hyperexcitable neurons tested. The effect of S(-)-Bay K 8644 was counteracted by both diltiazem (in 6 of 6 neurons) and nimodipine (in 5 of 5 neurons). 4) These data show that antagonists at both the N- and the L-type voltage dependent calcium channels influence the spinal processing of input from the knee joint. The data suggest, therefore, that voltage-dependent calcium channels of both the N- and the L-type are important for the sensory functions of the spinal cord. They are involved in the spinal processing of non-nociceptive as well as nociceptive mechanosensory input from the joint, both under normal and inflammatory conditions. The present results show in particular that N- and L- type channels are likely to be involved in the generation of pain evoked by noxious mechanical stimulation in normal tissue as well as in the mechanical hyperalgesia that is usually present during inflammation.

Received 26 February 1996; accepted in final form 30 July 1996.
APS Manuscript Number J151-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996