Antinociceptive actions of descending dopaminergic tracts on cat and rat dorsal horn somatosensory neurones.

Abstract

SUMMARY1. The actions of dopamine (DA) and DA receptor specific agonists and antagonist ionophoretically applied in the spinal dorsal horn, and of focal electrical stimulation in the region of the supraspinal DA cell groups (A9 and All) were assessed on the somatosensory responses of dorsal horn neurones, in both the rat and cat. The neurones tested were multireceptive, giving reproducible responses to both noxious (using a mechanical pinch or radiant heat) and innocuous (using a motorized brush) cutaneous stimuli, as well as to ionophoretically applied DL-homocysteic acid (DLH, a direct excitant). In the cat, all neurones tested were identified as belonging to the spinocervical tract (SCT) and were located in the dorsal horn laminae III-V, whilst in the rat, spinothalamic tract (STT) and spinomesencephalic (SMT) neurones located in the region of lamina I and laminae Ill-V were tested.2. lonophoretically applied DA and RU24213, a D2 DA receptor agonist, caused a selective inhibition of the responses to noxious stimuli of SCT, STT and SMT neurones, whilst the responses to non-nociceptive stimuli, spontaneous activity and DLH-evoked activity were unaffected. This action was reversed in the presence of sulpiride, the highly selective D2 DA receptor antagonist. Neither sulpiride alone nor SKF38393, a D1 DA receptor agonist, altered evoked or spontaneous activity when ionophoretically applied.3. Focal electrical stimulation in the region of the All, but not the A9, DA cell group selectively suppressed nociceptive responses of spinal, multireceptive neurones in the rat. This stimulus-evoked effect was consistently and rapidly reversed by ionophoresis of sulpiride, in the vicinity of the dorsal horn neurone being tested. In contrast, naloxone and idazoxan (RX781094), an oc2-antagonist, were not effective.4. This study presents data supporting a selective antinociceptive role for DA at the spinal level, where it has a widespread antinociceptive influence, on cells in both the superficial and deeper dorsal horn. The Al1 DA cell group was shown to be a supraspinal site from which a selective antinociceptive action could be electrically evoked and which was mediated by DA at the level of the dorsal horn.

Neurons of the Dopaminergic/Calcitonin Gene-Related Peptide A11 Cell Group Modulate Neuronal Firing in the Trigeminocervical Complex: An Electrophysiological and Immunohistochemical Study

“…The data are consistent with the A11 providing a descending D 2 receptor family-mediated tonic modulation of ophthalmic division trigeminal nociceptive afferents. The data are consistent with rat and cat spinal cord studies in which focal electrical stimulation in the region of the A11 dopamine cell group suppressed the nociceptive but not non-nociceptive responses of multireceptive neurons in the spinal cord dorsal horn (Fleetwood-Walker et al, 1988). The colocalization of CGRP in the A11 and the recently confirmed role for CGRP in migraine (Bigal et al, 2008;Ho et al, 2008), taken with other data on dopamine in migraine (Peroutka, 1997), suggest a possible role for the A11 in the disorder.…”

“…As D 2 -like receptors (D 2 , D 3 , D 4 receptors) normally cause hyperpolarization and inhibit cell firing via an inhibition of cAMP formation (Missale et al, 1998), this suggests the A11 inhibitory effect is mediated by activation of D 2 -like receptors in the TCC. This interpretation is supported by data in the rat and cat spinal cord, in which the stimulus-evoked A11 effect was consistently and rapidly reversed by iontophoresis of a selective D 2 receptor antagonist (sulpiride) in the vicinity of the dorsal horn neurons tested (Fleetwood-Walker et al, 1988). Furthermore, iontophoretically applied dopamine or a D 2 receptor agonist (RU24213 [N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride]) in the rat and cat spinal cord caused inhibition of nociceptive responses in these spinal cord neurons, reversed by a selective D 2 receptor antagonist.…”

Expression and distribution of all dopamine receptor subtypes (D1–D5) in the mouse lumbar spinal cord: A real-time polymerase chain reaction and non-autoradiographic in situ hybridization study

“…There are extensive dopaminergic projections in the spinal cord (Skagerberg et al, 1982, Skagerberg and Bjorklund, 1985, Skagerberg et al, 1988, and a number of authors have demonstrated modulatory actions of dopamine in the cord (Carp and Anderson, 1982, Barasi and Duggal, 1985, Fleetwood-Walker et al, 1988, Hasegawa et al, 1990, Skoog and Noga, 1995, Kemnitz, 1997, Garraway and Hochman, 2001, Tamae et al, 2005. However, there is only a limited description on the distribution of the different dopamine receptors in spinal cord neurons (Dubois et al, 1986, Schambra et al, 1994, Yokoyama et al, 1994, van Dijken et al, 1996, Levant and McCarson, 2001, Zhao et al, 2007.…”

Monoaminergic Control of Cauda-Equina-Evoked Locomotion in the Neonatal Mouse Spinal Cord

“…At least a portion of these fibers are likely functional because stimulation of the parapyramidal area in the brain stem elicits 5-HT-dependent locomotor-like activity (Liu and Jordan 2005) and separate studies confirm the release of 5-HT and NA metabolites in the ventral horn of adult and neonatal rats during brain stem stimulation or exercise (Gerin et al 1994(Gerin et al , 1995Jordan and Schmidt 2002). Less data are available for the dopaminergic system; however, DA fibers and receptors are present in the rat spinal cord (Holstege et al 1996;Ridet et al 1992;Yoshida and Tanaka 1988) and are functional (Fleetwood-Walker et al 1988). The extent to which DA, 5-HT, or NA contributes to reflex and network modulation in the intact neonate is unknown.…”