The role of spinal cord 5-HT1A and 5-HT1B receptors in the modulation of a spinal nociceptive reflex

Eide, Per Kristian; Joly, Norma Mjellem; Hole, Kjell

doi:10.1016/0006-8993(90)90025-7

Cited by 64 publications

(9 citation statements)

References 29 publications

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“…Using a tail-flick rodent model, Eide et al demonstrated that intrathecal injection of 5-HT1A and 5-HT1B receptor agonists could suppress the nociceptive tail-flick reflex at the spinal cord level, but none of them can change the temperature of tail skin (30). Dogrul et al reported that the administration of the 5-HT7 receptor antagonist SB-269970 could inhibit the antinociceptive effect produced by systemic morphine administration, indicating that the spinal 5-HT7 receptor influences systemic morphine-induced antinociceptive actions (31).…”

Section: Animal Model Of 5-ht and Ne In Somatic Symptomsmentioning

confidence: 99%

Dysfunction in Serotonergic and Noradrenergic Systems and Somatic Symptoms in Psychiatric Disorders

et al. 2019

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Somatic symptoms include a range of physical experiences, such as pain, muscle tension, body shaking, difficulty in breathing, heart palpitation, blushing, fatigue, and sweating. Somatic symptoms are common in major depressive disorder (MDD), anxiety disorders, and some other psychiatric disorders. However, the etiology of somatic symptoms remains unclear. Somatic symptoms could be a response to emotional distress in patients with those psychiatric conditions. Increasing evidence supports the role of aberrant serotoninergic and noradrenergic neurotransmission in somatic symptoms. The physiological alterations underlying diminished serotonin (5-HT) and norepinephrine (NE) signaling may contribute to impaired signal transduction, reduced 5-HT, or NE release from terminals of presynaptic neurons, and result in alternations in function and/or number of receptors and changes in intracellular signal processing. Multiple resources of data support each of these mechanisms. Animal models have shown physiological responses, similar to somatic symptoms seen in psychiatric patients, after manipulations of 5-HT and NE neurotransmission. Human genetic studies have identified many single-nucleotide polymorphisms risk loci associated with somatic symptoms. Several neuroimaging findings support that somatic symptoms are possibly associated with a state of reduced receptor binding. This narrative literature review aimed to discuss the involvement of serotonergic and noradrenergic systems in the pathophysiology of somatic symptoms. Future research combining neuroimaging techniques and genetic analysis to further elucidate the biological mechanisms of somatic symptoms and to develop novel treatment strategies is needed.

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Section: Animal Model Of 5-ht and Ne In Somatic Symptomsmentioning

confidence: 99%

Dysfunction in Serotonergic and Noradrenergic Systems and Somatic Symptoms in Psychiatric Disorders

et al. 2019

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“…Eide et al [ 33 ] examined whether injection of 5-HT 1A and 5-HT 1B receptor agonists in mice had the ability to alter the tail-flick reflex, and whether effects on the reflex latency involve changes in tail skin temperature. These authors found that in mouse, both 5-HT 1A and 5-HT 1B receptor agonists inhibit the nociceptive tail-flick reflex when administered into the spinal subarachnoid space, and the effect does not depend on changes in tail skin temperature.…”

Section: Activity Of Serotoninergic Receptors In the Modulation Of Pamentioning

confidence: 99%

Review: 5-HT1, 5-HT2, 5-HT3 and 5-HT7 Receptors and their Role in the Modulation of Pain Response in the Central Nervous System

et al. 2018

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Background:The aim of this review was to identify the mechanisms by which serotonin receptors involved at the central level are able to modulate the nociceptive response. Pain is a defense mechanism of the body that entails physio-logical, anatomical, neurochemical, and psychological changes, and is defined as an unpleasant sensory and emotional expe-rience with potential risk of tissue damage, comprising the leading cause of appointments with Physicians worldwide. Treatment for this symptom has generated several neuropharmacological lines of research, due to the different types of pain and the various drugs employed to treat this condition. Serotonin [5-HydroxyTryptamine (5-HT)] is a neurotransmitter with seven families (5-HT1–5-HT7) and approximately 15 receptor subtypes. Serotonin modulates neuronal activity; however, this neurotransmitter is related with a number of physiological processes, such as cardiovascular function, gastric motility, renal function, etc. On the other hand, several researches reported that serotonin modulates nociceptive response through 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the Central Nervous System (CNS).Method:In this review, a search was conducted on PubMed, ProQuest, EBSCO, and the Science Citation Index for studies evaluating the effects of 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the CNS on the modulation of different types of pain.ConclusionWe concluded that 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the CNS modulate the pain, but this depends on the distribution of the receptors, dose of agonists or antagonists, administration route, pain type and duration in order to inhibit, excite, or even maintain the nociceptive response.

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“…5-HT 1A receptors are widely distributed in the central nervous system, being localized in raphe nuclei as somatodendritic receptors (Riad et al, 2000), or in cortical and limbic areas as post-synaptic receptors (Verge et al, 1985;Radja et al, 1991;Miquel et al, 1992). The wide regional expression of 5-HT 1A receptors is in accordance with their involvement in many physiological functions, including cognition (Buhot, 1997), cognitive behaviors (Buhot, 1997), pain (Kristian Eide et al, 1990) and in numerous brain disorders such as anxiety (Akimova et al, 2009), depression (Richardson-Jones et al, 2010), schizophrenia (Maćkowiak et al, 2000), Alzheimer's disease (Truchot et al, 2007), and Parkinson's disease (Shimizu and Ohno, 2013). In view of the complexity of the functions controlled by 5-HT 1A receptors, efforts have been made to investigate them using various positron emission tomography (PET) imaging tools, notably as concerns the fluctuations of endogenous neurotransmitter levels in physiological or pathological conditions.…”

Section: Introductionmentioning

confidence: 99%

[18F]F13640, a 5-HT1A Receptor Radiopharmaceutical Sensitive to Brain Serotonin Fluctuations

et al. 2021

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IntroductionSerotonin is involved in a variety of physiological functions and brain disorders. In this context, efforts have been made to investigate the in vivo fluctuations of this neurotransmitter using positron emission tomography (PET) imaging paradigms. Since serotonin is a full agonist, it binds preferentially to G-protein coupled receptors. In contrast, antagonist PET ligands additionally interact with uncoupled receptors. This could explain the lack of sensitivity to serotonin fluctuations of current 5-HT1A radiopharmaceuticals which are mainly antagonists and suggests that agonist radiotracers would be more appropriate to measure changes in neurotransmitter release. The present study evaluated the sensitivity to endogenous serotonin release of a recently developed, selective 5-HT1A receptor PET radiopharmaceutical, the agonist [18F]F13640 (a.k.a. befiradol or NLX-112).Materials and MethodsFour cats each underwent three PET scans with [18F]F13640, i.e., a control PET scan of 90 min, a PET scan preceded 30 min before by an intravenous injection 1 mg/kg of d-fenfluramine, a serotonin releaser (blocking challenge), and a PET scan comprising the intravenous injection of 1 mg/kg of d-fenfluramine 30 min after the radiotracer injection (displacement challenge). Data were analyzed with regions of interest and voxel-based approaches. A lp-ntPET model approach was implemented to determine the dynamic of serotonin release during the challenge study.ResultsD-fenfluramine pretreatment elicited a massive inhibition of [18F]F13640 labeling in regions known to express 5-HT1A receptors, e.g., raphe nuclei, hippocampus, thalamus, anterior cingulate cortex, caudate putamen, occipital, frontal and parietal cortices, and gray matter of cerebellum. Administration of d-fenfluramine during PET acquisition indicates changes in occupancy from 10% (thalamus) to 31% (gray matter of cerebellum) even though the dissociation rate of [18F]F13640 over the 90 min acquisition time was modest. The lp-ntPET simulation succeeded in differentiating the control and challenge conditions.ConclusionThe present findings demonstrate that labeling of 5-HT1A receptors with [18F]F13640 is sensitive to serotonin concentration fluctuations in vivo. Although the data underline the need to perform longer PET scan to ensure accurate measure of displacement, they support clinical development of [18F]F13640 as a tool to explore experimental paradigms involving physiological or pathological (neurological or neuropsychiatric pathologies) fluctuations of extracellular serotonin.

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The role of spinal cord 5-HT1A and 5-HT1B receptors in the modulation of a spinal nociceptive reflex

Cited by 64 publications

References 29 publications

Dysfunction in Serotonergic and Noradrenergic Systems and Somatic Symptoms in Psychiatric Disorders

Dysfunction in Serotonergic and Noradrenergic Systems and Somatic Symptoms in Psychiatric Disorders

Review: 5-HT1, 5-HT2, 5-HT3 and 5-HT7 Receptors and their Role in the Modulation of Pain Response in the Central Nervous System

[18F]F13640, a 5-HT1A Receptor Radiopharmaceutical Sensitive to Brain Serotonin Fluctuations

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