Serotonergic innervation of the dorsal horn of rat spinal cord: light and electron microscopic immunocytochemical study

Marlier, L.; Sandillon, F.; Poulat, P.; Rajaofetra, N.; Geffard, M.; Privat, Alain

doi:10.1007/bf01235548

Cited by 139 publications

(59 citation statements)

References 51 publications

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“…1E) and it is also well established that the descending serotonergic inhibitory pathways participate in the inhibition of pain transmission at the spinal level [32][33][34][35]. In our data, unlike the GABA receptor antagonist, methylsergide, the serotonin receptor antagonist did not show a significant effect on tactile sensitivity (Fig.…”

Section: Discussionsupporting

confidence: 58%

Transplantation of GABAergic Neurons from ESCs Attenuates Tactile Hypersensitivity Following Spinal Cord Injury

et al. 2010

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We investigated the therapeutic potential of mouse ESCderived gamma-amino butyric acid (GABA)ergic neurons ($74% of total neurons in vitro) to reduce neuropathic pain following spinal cord injury (SCI) in rats. Spinal cord hemisection at the T13 segment, which is used as a rat SCI pain model, induced tactile hypersensitivity of the hind paw, as evidenced by decreased paw withdrawal thresholds in response to von Frey filaments, and also induced hyperexcitability of wide dynamic range neurons in the lumbar spinal cord in response to natural cutaneous stimuli. At 2 weeks posthemisection, GABAergic neurons (500,000 cells) were transplanted into the subarachnoid space of the spinal lumbar enlargement via a modified lumbar puncture technique. The transplantation of GABAergic neurons led to long-term attenuation of hemisection-induced tactile hypersensitivity and neuronal hyperexcitability as compared with vehicle-treated controls. These attenuations were reversed by the application of bicuculline and CGP52432, GABA-A and GABA-B receptor antagonists, respectively, but not by application of the serotonergic receptor antagonist methylsergide, indicating a specific restoration of spinal GABAergic inhibition. Histological data from sections of the lumbar cord in grafts demonstrated that 43.5% of surviving engrafted cells were neurons and located densely in the lower-medial portion of the dorsal funiculi in the spinal white matter. Among the observed neurons, 26.2% were GABAergic. The results suggest that subarachnoid transplantation of ESC-derived GABAergic neurons appear to restore spinal GABAergic inhibitory tone and can be a promising strategy to treat SCI-induced pain.

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Section: Discussionsupporting

confidence: 58%

Transplantation of GABAergic Neurons from ESCs Attenuates Tactile Hypersensitivity Following Spinal Cord Injury

et al. 2010

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“…To date, three 5-HT subtypes have been detected in the spinal network involved in ejaculation. 5-HT1A, -1B, and -2C receptors are densely expressed in the sacral parasympathetic nucleus and motoneurons of Onuf's nucleus (Marlier et al, 1991;Thor et al, 1993;Ridet et al, 1994;Bancila et al, 1999). In addition, high density of 5-HT1B receptors has been described in lamina X of the lumbar spinal cord, which includes SGE area (Marlier et al, 1991).…”

Section: B Spinal Cordmentioning

confidence: 93%

“…5-HT1A, -1B, and -2C receptors are densely expressed in the sacral parasympathetic nucleus and motoneurons of Onuf's nucleus (Marlier et al, 1991;Thor et al, 1993;Ridet et al, 1994;Bancila et al, 1999). In addition, high density of 5-HT1B receptors has been described in lamina X of the lumbar spinal cord, which includes SGE area (Marlier et al, 1991). After a series of experiments investigating the role of 5-HT in a model of expulsion reflex in rat (urethrogenital reflex), it was suggested that 5-HT released in lumbosacral segments from terminals of neurons lying in the ventrolateral medulla exerts an inhibitory tone on ejaculation McKenna, 1990, 1992;Gravitt and Marson, 2007).…”

Section: B Spinal Cordmentioning

confidence: 99%

Pharmacology for the Treatment of Premature Ejaculation

Giuliano

Clément

2012

Pharmacol Rev

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“…Indeed most 5HT varicosities establish nonsynaptic contacts with dorsal horn neurons (Marlier et al, 1991;Ridet et al, 1993). Even though some 5HT neurons clearly act via conventional synapses (Jankowska et al, 1995;Maxwell and Jankowska, 1996), there appears to be a predominant nonsynaptic "volume transmission" mechanism that operates (Fuxe and Agnati, 1991).…”

Section: Technical Considerationsmentioning

confidence: 99%

Genetically expressed transneuronal tracer reveals direct and indirect serotonergic descending control circuits

Bráz

Basbaum

2008

J of Comparative Neurology

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Despite the evidence for a significant contribution of brainstem serotonergic (5HT) systems to the control of spinal cord "pain" transmission neurons, attention has turned recently to the influence of nonserotonergic neurons, including the facilitatory and inhibitory controls that originate from socalled "on" and "off" cells of the rostroventral medulla (RVM). Unclear, however, is the extent to which these latter circuits interact with or are influenced by the serotonergic cell groups. To address this question we selectively targeted expression of a transneuronal tracer, wheat germ agglutinin (WGA), in the 5HT neurons so as to study the interplay between the 5HT and non-5HT systems. In addition to confirming the direct medullary 5HT projection to the spinal cord we also observed large numbers of non-5HT neurons, in the medullary nucleus reticularis gigantocellularis and magnocellularis, that were WGA-immunoreactive, i.e., were transneuronally labeled from 5HT neurons. Fluoro-Gold injections into the spinal cord established that these reticular neurons are not only postsynaptic to the 5HT neurons of the medulla, but that most are also at the origin of descending, bulbospinal pathways. By contrast, we found no evidence that neurons of the midbrain periaqueductal gray that project to the RVM are postsynaptic to midbrain or medullary 5HT neurons. Finally, we found very few examples of WGA-immunoreactive noradrenergic neurons, which suggests that there is considerable independence of the monoaminergic bulbospinal pathways. Our results indicate that 5HT neurons influence "pain" processing at the spinal cord level both directly and indirectly via feedforward connections with multiple non-5HT descending control pathways. Indexing termsWGA; pain; serotonin; brainstem; analgesia; RVM Until recently, studies of the bulbospinal systems that originate from the rostral ventral medulla (RVM) emphasized their contribution to inhibitory control of "pain" transmission. HHS Public AccessAuthor manuscript J Comp Neurol. Author manuscript; available in PMC 2016 July 16. Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptMost important, opioid injection into or electrical stimulation of the midbrain periaqueductal gray (PAG) activates these descending pathways and concurrently produces a profound antinociceptive action, including inhibition of the firing of dorsal horn nociresponsive neurons and behavioral analgesia (Basbaum and Fields, 1984). Although neurochemically distinct pathways arise from the RVM, considerable evidence pointed to the contribution of medullary serotonergic neurons. For example, morphine evokes the release of serotonin at the level of the spinal cord and RVM (Matos et al., 1992;Taylor and Basbaum, 2003) and serotonin depletion using pharmacological or ablative procedures blocks the analgesia induced by systemic administration of morphine (Vogt, 1974;Proudfit and Anderson, 1975;Yaksh et al., 1977).In agreement with these findings, Zhao et al. (2007a,b) reported that inflammatory pai...

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Serotonergic innervation of the dorsal horn of rat spinal cord: light and electron microscopic immunocytochemical study

Cited by 139 publications

References 51 publications

Transplantation of GABAergic Neurons from ESCs Attenuates Tactile Hypersensitivity Following Spinal Cord Injury

Transplantation of GABAergic Neurons from ESCs Attenuates Tactile Hypersensitivity Following Spinal Cord Injury

Pharmacology for the Treatment of Premature Ejaculation

Genetically expressed transneuronal tracer reveals direct and indirect serotonergic descending control circuits

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