A. Dickenson, C. Hughes, A. Rueff
Dec 1, 1990
Citations
1
Influential Citations
40
Citations
Quality indicators
Journal
Pain
Abstract
&NA; We have studied the effect of NE 19550 (olvanil, N‐(4‐hydroxy‐3‐methoxyphenyl) methyl‐9Z‐octadecenamide), a capsaicin analogue with approximately equipotent antinociceptive activity in vivo compared with capsaicin, on nociceptive responses recorded from spinal dorsal horn neurones in vivo and from a spinal ventral root in vitro. In adult rats anaesthetized with halothane, antinociceptive doses of olvanil (20–40 &mgr;mol/kg, s.c.) reduced C‐fibre responses evoked in wide dynamic range, lumbar dorsal horn neurones, by peripheral transcutaneous electrical stimulation. Intradermal injection of olvanil, localized to a discrete region of the peripheral receptive field, did not activate C‐fibres nor change C‐fibre evoked activation of dorsal horn neurones. Spinal intrathecal administration of olvanil attenuated C‐fibre evoked responses and, at the highest concentration, significantly reduced A&bgr;‐fibre evoked activity. In the neonatal rat spinal cord/tail preparation maintained in vitro, superfusion of the cord with olvanil (500 nM‐5 &mgr; M) did not evoke a depolarization but responses to peripheral noxious stimulation were attenuated. In a similar in vitro preparation of the neonatal rat spinal cord, the release of calcitonin gene‐related peptide‐like immunoreactivity (CGRP‐LI) was measured in spinal cord superfusates. Capsaicin (2–10 &mgr;M) evoked a large release of CGRP‐LI but olvanil (2–10 &mgr;M) produced only a small or undetectable release. Following the administration of each substance, however, the release of CGRP‐LI evoked by a depolarizing potassium stimulus was significantly attenuated. These data indicate that C‐fibre input to the dorsal horn was attenuated by acute systemic doses of olvanil that were antinociceptive in behavioural tests. This effect was unlikely to be due to impairment of C‐fibre function by a peripheral locus of action but was more consistent with an action in the spinal cord in which the reduced release of a neurotransmitter substance from afferent nerve terminals may play a prominent role.