Spinal application of ω-conotoxin GVIA, an N-type calcium channel antagonist, attenuates enhancement of dorsal spinal neuronal responses caused by intra-articular injection of mustard oil in the rat

Abstract

Administration of the N-type calcium channel antagonist omega-conotoxin GVIA to the spinal cord reduces spinal neuronal responses to innocuous and noxious pressure applied to the knee, both in rats with normal knees and in rats in which a knee inflammation has induced a state of hyperexcitability in spinal neurons (Neugebauer et al. 1996, J Neurophysiol 76: 3740-3749). In the present experiments we studied whether the development of hyperexcitability of spinal neurons induced by intra-articular injection of mustard oil, an excitant of C-fibres, can be influenced by spinal pretreatment with omega-conotoxin GVIA. In anaesthetized rats, responses of wide-dynamic-range neurons were recorded in the spinal dorsal horn when standardized stimulation with innocuous and noxious pressure was applied to the knee and ankle joints. Injection of mustard oil into the knee joint cavity caused an initial neuronal discharge followed by an early (peaking at about 15 min) and a late (after 60 min) facilitation of responses to innocuous and noxious stimulation of the knee. Responses to ankle stimulation showed only the late facilitation. When omega-conotoxin GVIA (20 microl, 1 microM) was applied into a small trough onto the spinal cord above the recording site the responses to articular stimulation were reduced. Furthermore, when mustard oil was injected while omega-conotoxin GVIA was on the spinal cord, the early increase in the neuronal responses to innocuous pressure on the knee and the late increase in responses to noxious pressure on the ankle were significantly smaller than those observed in rats not treated with omega-conotoxin GVIA; the drop in the responses to noxious pressure on the knee was not significant. Thus the spinal application of omega-conotoxin GVIA reduced but did not completely prevent the fast and slow development of neuronal hyperexcitability of spinal cord neurons produced by a prompt and strong excitation of afferent C-fibres. This suggests that N-type calcium channels are important for the development of spinal cord hyperexcitability.