Serotonin induces peripheral mechanical antihyperalgesic effects in mice

Diniz, Danielle Aguiar; Petrocchi, Júlia Alvarenga; Navarro, Larissa Caldeira; Souza, Tâmara Cristina; Castor, Marina Gomes Miranda e; Perez, Andréa C.; Duarte, Igor Dimitri Gama; Romero, Thiago Roberto Lima

doi:10.1016/j.ejphar.2015.10.012

Cited by 22 publications

(7 citation statements)

References 17 publications

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“…Here we demonstrated the involvement of the peripheral 5-HT2 (partially) and 5-HT3 receptors in the antinociceptive effect of BDS 391 in the PGE 2 -induced hyperalgesia. Our results are supported by data from the literature demonstrating that inhibition of prostaglandin E 2 -induced hyperalgesia by the peripheral administration of low doses of serotonin is mediated by activation of 5-HT2A and 5-HT3 receptors [ 18 ]. It is important to stress that mRNA for serotonin receptors, including 5-HT2 and 5-HT3 receptors, has been detected in dorsal root ganglia, as well as the presence of those receptors in unmyelinated nerve fibers [ 44 , 45 ].…”

Section: Discussionsupporting

confidence: 87%

“…The role of serotonin in pain and analgesia, although controversial, is well recognized. The effect of 5-HT on nociception depends on the subtype of receptor activated by this amine and also on the localization (central or peripheral) of the receptors in the nervous system [ 15 , 16 , 17 , 18 ]. The 5-HT receptors belong to a family of seven receptors (5-HT1 to 5-HT7) that are subdivided into 14 subtypes [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to those data, Tzeng et al, in 2017 [ 31 ], demonstrated, in rats, that subcutaneous injection of serotonin causes, in a dose-dependent manner, a local inhibition of the cutaneous trunci muscle reflex induced by skin pinprick, indicating an antinociceptive effect for this amine. In this sense, Diniz et al, in 2015 [ 18 ], have also demonstrated, in mice, that peripheral (intraplantar) administration of low doses of serotonin inhibits prostaglandin E2-induced hyperalgesia by activation of 5-HT1B, 5-HT2A and 5-HT3 receptors. In addition to the data from Diniz et al, the role of 5-HT1B/1D receptors in analgesia was also demonstrated in models of thermal hyperalgesia induced by carrageenan [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

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Peripheral 5-HT3 Receptors Are Involved in the Antinociceptive Effect of Bunodosine 391

Ferreira

Zaharenko

Kazuma

et al. 2017

Toxins

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Bunodosine 391 (BDS 391), a low molecular weight compound isolated from the sea anemone Bunodosoma cangicum, increases the nociceptive threshold and inhibits inflammatory hyperalgesia. Serotonin receptors are involved in those effects. In this study, we have expanded the characterization of the antinociceptive effect of BDS 391 demonstrating that, in rats: (a) the compound inhibits (1.2–12 ng/paw) overt pain, in the formalin test, and mechanical hyperalgesia (0.6–6.0 ng/paw) detected in a model of neuropathic pain; (b) intraplantar administration of ondansetron, a selective 5-HT3 receptor antagonist, blocks the effect of BDS 391, whereas ketanserin, a 5-HT2 receptor antagonist, partially reversed this effect, indicating the involvement of peripheral 5-HT2 and 5-HT3 receptors in BDS 391 antinociception; and (c) in binding assay studies, BDS 391 was not able to displace the selective 5-HT receptor antagonists, suggesting that this compound does not directly bind to these receptors. The effect of biguanide, a selective 5-HT3 receptor agonist, was also evaluated. The agonist inhibited the formalin’s nociceptive response, supporting an antinociceptive role for 5-HT3 receptors. Our study is the first one to show that a non-peptidic low molecular weight compound obtained from a sea anemone is able to induce antinociception and that activation of peripheral 5-HT3 receptors contributes to this effect.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Peripheral 5-HT3 Receptors Are Involved in the Antinociceptive Effect of Bunodosine 391

Ferreira

Zaharenko

Kazuma

et al. 2017

Toxins

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“…Serotonin, dopamine, cannabinoid, and metabotropic glutamate receptors are involved in mechanisms of short and long-term memory, memory consolidation, and learning (Abush and Akirav, 2009; Leung and Wong, 2017). Opioid and serotonin receptors are involved in the perception and processing of pain (Dong et al, 2001; Diniz et al, 2015). Most GPCRs, including dopamine, serotonin, and opioid receptors also play a prominently role on modulating and influencing behavior and emotions (Baik, 2013; Chu Sin Chung and Kieffer, 2013; Nautiyal et al, 2015).…”

Section: Brain-enriched Gpcrs Coupled To Gi/omentioning

confidence: 99%

Gi/o-Protein Coupled Receptors in the Aging Brain

Oliveira

Ramos

et al. 2019

Front. Aging Neurosci.

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Cells translate extracellular signals to regulate processes such as differentiation, metabolism and proliferation, via transmembranar receptors. G protein-coupled receptors (GPCRs) belong to the largest family of transmembrane receptors, with over 800 members in the human species. Given the variety of key physiological functions regulated by GPCRs, these are main targets of existing drugs. During normal aging, alterations in the expression and activity of GPCRs have been observed. The central nervous system (CNS) is particularly affected by these alterations, which results in decreased brain functions, impaired neuroregeneration, and increased vulnerability to neuropathologies, such as Alzheimer’s and Parkinson diseases. GPCRs signal via heterotrimeric G proteins, such as G o , the most abundant heterotrimeric G protein in CNS. We here review age-induced effects of GPCR signaling via the G i/o subfamily at the CNS. During the aging process, a reduction in protein density is observed for almost half of the G i/o -coupled GPCRs, particularly in age-vulnerable regions such as the frontal cortex, hippocampus, substantia nigra and striatum. G i/o levels also tend to decrease with aging, particularly in regions such as the frontal cortex. Alterations in the expression and activity of GPCRs and coupled G proteins result from altered proteostasis, peroxidation of membranar lipids and age-associated neuronal degeneration and death, and have impact on aging hallmarks and age-related neuropathologies. Further, due to oligomerization of GPCRs at the membrane and their cooperative signaling, down-regulation of a specific G i/o -coupled GPCR may affect signaling and drug targeting of other types/subtypes of GPCRs with which it dimerizes. G i/o -coupled GPCRs receptorsomes are thus the focus of more effective therapeutic drugs aiming to prevent or revert the decline in brain functions and increased risk of neuropathologies at advanced ages.

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“…Previous animal studies have demonstrated that the noradrenergic descending inhibitory pathway plays an important role in analgesic action [ 38 ]. In addition, activation of serotonin receptors, such as 5-HT1, 5-HT2, and 5-HT3, induces analgesic effects [ 39 , 40 ]. In 2009, Hagiwara et al [ 41 ] performed an animal study in rats to evaluate the mechanism of PRF action.…”

Section: Pain-reducing Mechanism Of Pulsed Radiofrequencymentioning

confidence: 99%

The mechanism of action of pulsed radiofrequency in reducing pain: a narrative review

Park

Chang

2022

J Yeungnam Med Sci

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Pain from nervous or musculoskeletal disorders is one of the most common complaints in clinical practice. Corticosteroids have a high pain-reducing effect, and their injection is generally used to control various types of pain. However, they have various adverse effects including flushing, hyperglycemia, allergic reactions, menstrual changes, immunosuppression, and adrenal suppression. Pulsed radiofrequency (PRF) is known to have a pain-reducing effect similar to that of corticosteroid injection, with nearly no major side effects. Therefore, it has been widely used to treat various types of pain, such as neuropathic, joint, discogenic, and muscle pain. In the current review, we outlined the pain-reducing mechanisms of PRF by reviewing previous studies. When PRF was first introduced, it was supposed to reduce pain by long-term depression of pain signaling from the peripheral nerve to the central nervous system. In addition, deactivation of microglia at the level of the spinal dorsal horn, reduction of proinflammatory cytokines, increased endogenous opioid precursor messenger ribonucleic acid, enhancement of noradrenergic and serotonergic descending pain inhibitory pathways, suppression of excitation of C-afferent fibers, and microscopic damage of nociceptive C- and A-delta fibers have been found to contribute to pain reduction after PRF application. However, the pain-reducing mechanism of PRF has not been clearly and definitely elucidated. Further studies are warranted to clarify the pain-reducing mechanism of PRF.

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Serotonin induces peripheral mechanical antihyperalgesic effects in mice

Cited by 22 publications

References 17 publications

Peripheral 5-HT3 Receptors Are Involved in the Antinociceptive Effect of Bunodosine 391

Peripheral 5-HT3 Receptors Are Involved in the Antinociceptive Effect of Bunodosine 391

Gi/o-Protein Coupled Receptors in the Aging Brain

The mechanism of action of pulsed radiofrequency in reducing pain: a narrative review

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