The differential effects of 5-hydroxytryptamine, noradrenaline and raphe stimulation on nociceptive and non-nociceptive dorsal horn interneurones in the cat

Belcher, G.; Ryall, R. W.; Schaffner, R.

doi:10.1016/0006-8993(78)90887-9

Cited by 333 publications

(46 citation statements)

References 31 publications

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“…Previous studies have demonstrated that electrical and chemical stimulation of the RVM or NRM result in an inhibition of spinal nociception (Fields et al, 1977;Belcher et al, 1978;Duggan and Griersmith, 1979;Rivot et al, 1980;Carstens et al, 1981;Hodge et al, 1983;Light et al, 1986;Zhuo and Gebhart, 1997). The mechanism of the antinociceptive effect is controversial, however, because many neurotransmitters in addition to 5-HT exist in raphe neurons that may contribute to the descending modulation of spinal sensory systems (e.g., GABA, glycine, acetylcholine, somatostatin, substance P, enkephalin, dynorphin, galanin, thyrotropin-releasing hormone, and cholecystokinin) (Millan, 2002).…”

Section: Discussionmentioning

confidence: 99%

Direct GABAergic and Glycinergic Inhibition of the Substantia Gelatinosa from the Rostral Ventromedial Medulla Revealed byIn VivoPatch-Clamp Analysis in Rats

et al. 2006

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Stimulation of the rostral ventromedial medulla (RVM) is believed to exert analgesic effects through the activation of the serotonergic system descending to the spinal dorsal horn; however, how nociceptive transmission is modulated by the descending system has not been fully clarified. To investigate the inhibitory mechanisms affected by the RVM, an in vivo patch-clamp technique was used to record IPSCs from the substantia gelatinosa (SG) of the spinal cord evoked by chemical (glutamate injection) and electrical stimulation (ES) of the RVM in adult rats. In the voltage-clamp mode, the RVM glutamate injection and RVM-ES produced an increase in both the frequency and amplitude of IPSCs in SG neurons that was not blocked by glutamate receptor antagonists. Serotonin receptor antagonists were unexpectedly without effect, but a GABA A receptor antagonist, bicuculline, or a glycine receptor antagonist, strychnine, completely suppressed the RVM stimulation-induced increase in IPSCs. The RVM-ES-evoked IPSCs showed fixed latency and no failure at 20 Hz stimuli with a conduction velocity of Ͼ3 m/s (3.1-20.7 m/s), suggesting descending monosynaptic GABAergic and/or glycinergic inputs from the RVM to the SG through myelinated fibers. In the current-clamp mode, action potentials elicited by noxious mechanical stimuli applied to the receptive field of the ipsilateral hindlimb were suppressed by the RVM-ES in more than half of the neurons tested (63%; 10 of 16). These findings suggest that the RVM-mediated antinociceptive effects on noxious inputs to the SG may be exerted preferentially by the direct GABAergic and glycinergic pathways to the SG.

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Section: Discussionmentioning

confidence: 99%

Direct GABAergic and Glycinergic Inhibition of the Substantia Gelatinosa from the Rostral Ventromedial Medulla Revealed byIn VivoPatch-Clamp Analysis in Rats

et al. 2006

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“…Prolonged excitatory actions of 5-HT on the peripheral endings of Group II, III and IV cutaneous afferents 2,10 and Group III and IV muscle afferents 9,25 have been observed with single fiber extracellular recordings in the cat. In the spinal cord, a role for 5-HT in presynaptic inhibition was previously proposed based on electrophysiological findings 3,30 and anatomical evidence 23 (but see ref. 31).…”

Section: Discussionmentioning

confidence: 99%

Serotonin depolarizes type A and C primary afferents: an intracellular study in bullfrog dorsal root ganglion

1985

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Intracellular recordings were obtained from the somata of type A and C primary afferents in the isolated bullfrog dorsal root ganglion (DRG) preparation. Bath application of serotonin (5-HT) in concentrations of 0.25-1.0 mM led to slow and fast depolarizing responses. Slow, maintained 5-HT depolarizations were observed in 47% of type A and 70% of type C neurons. These slow depolarizations were associated with an underlying increase in input resistance (R in ) In some type A neurons, the R in increase was masked by a decrease in R in due to depolarization-induced rectification. The slow 5-HT depolarization of type A, but not type C neurons showed pronounced tachyphylaxis to repeated 5-HT applications. In type C afferents, serotonin's slow action was often accompanied by spontaneous firing. Manganese decreased slow 5-HT depolarizations of both cell types. A slow depolarization and excitation of type C afferents by methysergide and cinanserin was also observed.Fast transient 5-HT depolarizations accompanied by a rapid decrease in R in were observed in 7% of type A and 24% of type C neurons. In some DRG cells the fast and slow depolarizations combined to form a biphasic response. The actions of 5-HT reported here resemble in some ways 5-HT responses recorded extracellularly from the spinal terminations of primary afferents.

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“…Electrophysiological experiments have shown that some interneurones (Biscoe, Curtis & Ryall, 1966;Randic & Yu, 1976;Belcher, Ryall & Schaffner, 1978) and motoneurones (Barasi & Roberts, 1974) are excited by 5-HT and Belcher et al (1978) have also suggested that 5-HT has a presynaptic inhibitory action on some primary afferents. It seems possible that the section and degeneration of dorsal roots removed the presynaptic inhibitory influence of iontophoretically applied 5-HT and, as a result, the postsynaptic excitatory effects of 5-HT appeared much larger.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Chronic Section of Dorsal Roots on the Responsiveness of Motoneurones to 5‐hydroxytryptamine and a Substance P Analogue

Roberts¹,

Wright²

1981

British J Pharmacology

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1 Experiments were performed on rats 14-21 days after unilateral dorsal root section in order to determine if the effects on motoneurone excitability of a substance P analogue, 5-hydroxytryptamine (5-HT) and noradrenaline were altered by section of primary afferents.2 The effects of iontophoretic applications of these agents on motoneurone excitability were quantified by measuring the change in amplitude of the short latency field potentials evoked antidromically, by ventral root stimulation. 3 lontophoretic application of the substance P analogue (eledoisin-related peptide, ERP) always produced an increase in the amplitude of the field potential. These increases in amplitude were 25.9% larger on the sides of the cords with sectioned dorsal roots. This was not a statistically significant difference (P>0.05). 4 Section of dorsal roots did not alter responses to noradrenaline. 5 Responses to 5-HT were significantly larger following section of dorsal roots. There is very little evidence for the release of 5-HT by primary afferents and denervation supersensitivity is an improbable explanation. It is possible that descending 5-HT systems directly excite motoneurones and indirectly inhibit primary afferent transmission. Dorsal root section would alter the balance between these actions of 5-HT in favour of an excitatory effect.

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The differential effects of 5-hydroxytryptamine, noradrenaline and raphe stimulation on nociceptive and non-nociceptive dorsal horn interneurones in the cat

Cited by 333 publications

References 31 publications

Direct GABAergic and Glycinergic Inhibition of the Substantia Gelatinosa from the Rostral Ventromedial Medulla Revealed byIn VivoPatch-Clamp Analysis in Rats

Direct GABAergic and Glycinergic Inhibition of the Substantia Gelatinosa from the Rostral Ventromedial Medulla Revealed byIn VivoPatch-Clamp Analysis in Rats

Serotonin depolarizes type A and C primary afferents: an intracellular study in bullfrog dorsal root ganglion

The Effects of Chronic Section of Dorsal Roots on the Responsiveness of Motoneurones to 5‐hydroxytryptamine and a Substance P Analogue

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