Serotonin enhances depolarizing spontaneous fluctuations, excitability, and ongoing activity in isolated rat DRG neurons via 5-HT4 receptors and cAMP-dependent mechanisms

Lopez, Elia R.; Carbajal, Anibal Garza; Tian, Jing; Bavencoffe, Alexis; Zhu, Michael X.; Dessauer, Carmen W.; Walters, Edgar T.

doi:10.1016/j.neuropharm.2020.108408

Cited by 28 publications

(32 citation statements)

References 56 publications

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“…In contrast, recent studies have reported a major role of the 5HT 3 receptor in mediating serotonergic pain and itch in TG and DRG neurons ( Domocos et al, 2020 , Kilinc et al, 2017 ). 5HT 4 and 5HT 7 have also recently been reported to play a role in serotonergic pain and itch ( Lopez et al, 2021 , Morita et al, 2015 , Ohta et al, 2006 ). Similar to 5HT 2A antagonism in our study, a 5HT 7 receptor antagonist reduced pain behaviors but did not alter CGRP release in cultured trigeminal ganglia neurons ( Wang et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Estrogen exacerbates the nociceptive effects of peripheral serotonin on rat trigeminal sensory neurons

Kaur

McDonald²,

Tongkhuya³

et al. 2021

Neurobiology of Pain

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Highlights 5HT-evoked nocifensive behaviors are sexually dimorphic and dependent on hormone status of the animal. Blocking the excitatory 5HT 2A receptor attenuates 5HT-evoked pain behaviors in females during proestrus/estrus. Basal levels of 5HT are elevated in cycling females as compared to males. Estrogen potentiates serotonergic neuromodulation of capsaicin-evoked CGRP release in female trigeminal sensory neurons.

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Section: Discussionmentioning

confidence: 99%

Estrogen exacerbates the nociceptive effects of peripheral serotonin on rat trigeminal sensory neurons

Kaur

McDonald²,

Tongkhuya³

et al. 2021

Neurobiology of Pain

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show abstract

“…The small change in input resistance is most likely related to the fact that deactivation of the G i/o pathway leads to the modulation of various ion conductances in neurons either directly or indirectly via disinhibition of adenylyl cyclase, an increase in intracellular cAMP levels and activation of PKA. This may involve modulation of GIRK, other K + channels 19,20 , TRPC [21][22][23] , HCN [24][25][26] , CNG 27 , voltage-gated Ca 2+ channels 28 as well as other PKA targets 29 . Epilepsy is a severe neurological disorder characterized by repeated seizures that affect about 1% of the population 30 .…”

Section: Discussionmentioning

confidence: 99%

Reverse optogenetics of G protein signaling by zebrafish non-visual opsin Opn7b for synchronization of neuronal networks

et al. 2021

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Opn7b is a non-visual G protein-coupled receptor expressed in zebrafish. Here we find that Opn7b expressed in HEK cells constitutively activates the Gi/o pathway and illumination with blue/green light inactivates G protein-coupled inwardly rectifying potassium channels. This suggests that light acts as an inverse agonist for Opn7b and can be used as an optogenetic tool to inhibit neuronal networks in the dark and interrupt constitutive inhibition in the light. Consistent with this prediction, illumination of recombinant expressed Opn7b in cortical pyramidal cells results in increased neuronal activity. In awake mice, light stimulation of Opn7b expressed in pyramidal cells of somatosensory cortex reliably induces generalized epileptiform activity within a short (<10 s) delay after onset of stimulation. Our study demonstrates a reversed mechanism for G protein-coupled receptor control and Opn7b as a tool for controlling neural circuit properties.

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“…Ectopic activity can originate from axons, in particular early after injury, but it can also emerge from the DRG soma (Amir et al, 2005). This likely happens due to changes in expression of ion channels in the DRG neuronal soma (Devor, 2006), or due to signaling events that cause the neuron to generate ectopic action potentials and instability in the resting membrane potential (Devor and Yarom, 2002; Odem et al, 2018; Garza Carbajal et al, 2020; Laumet et al, 2020; Lopez et al, 2021). Our previous work clearly showed that human DRG neuron somata from neuropathic pain patients could display ectopic activity, even after surgical removal and culturing (North et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

RNA Profiling of Neuropathic Pain-Associated Human DRGs Reveal Sex-differences in Neuro-immune Interactions Promoting Pain

Ray

Shiers

Ferreira

et al. 2021

Preprint

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Neuropathic pain is a leading cause of high impact pain, is often disabling and is poorly managed by current therapeutics. Here we focused on a unique group of neuropathic pain patients undergoing thoracic vertebrectomy where the DRG is removed as part of the surgery allowing for molecular characterization and identification of mechanistic drivers of neuropathic pain independently of preclinical models. Our goal was to quantify whole transcriptome RNA abundances using RNA-seq in pain-associated human DRGs from these patients, allowing comprehensive identification of molecular changes in these samples by contrasting them with non-pain associated DRGs. We sequenced 70 human DRGs, including over 50 having mRNA libraries with neuronal mRNA. Our expression analysis revealed profound sex differences in differentially expressed genes including increase of IL1B, TNF, CXCL14, and OSM in male and including CCL1, CCL21, PENK and TLR3 in female DRGs associated with neuropathic pain. Co-expression modules revealed enrichment in members of JUN-FOS signaling in males, and centromere protein coding genes in females. Neuro-immune signaling pathways revealed distinct cytokine signaling pathways associated with neuropathic pain in males (OSM, LIF, SOCS1) and females (CCL1, CCL19, CCL21). We validated cellular expression profiles of a subset of these findings using RNAscope in situ hybridization. Our findings give direct support for sex differences in underlying mechanisms of neuropathic pain in patient populations.

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Serotonin enhances depolarizing spontaneous fluctuations, excitability, and ongoing activity in isolated rat DRG neurons via 5-HT4 receptors and cAMP-dependent mechanisms

Cited by 28 publications

References 56 publications

Estrogen exacerbates the nociceptive effects of peripheral serotonin on rat trigeminal sensory neurons

Estrogen exacerbates the nociceptive effects of peripheral serotonin on rat trigeminal sensory neurons

Reverse optogenetics of G protein signaling by zebrafish non-visual opsin Opn7b for synchronization of neuronal networks

RNA Profiling of Neuropathic Pain-Associated Human DRGs Reveal Sex-differences in Neuro-immune Interactions Promoting Pain

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