Spinal TASK-1 and TASK-3 modulate inflammatory and neuropathic pain

García, Guadalupe; Noriega‐Navarro, Roxana; Martínez-Rojas, Vladimir A.; Gutiérrez-Lara, Erika J.; Oviedo, Norma; Murbartián, Janet

doi:10.1016/j.ejphar.2019.172631

Cited by 12 publications

(13 citation statements)

References 60 publications

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“…Employing a ribosomal profiling technique, Uttam and his colleagues [ 64 ] identify 31 genes whose proteins are downregulated after SNI in mouse DRGs. Among those 31 genes, 29 genes such as TSK3 [ 65 ] show no change of their mRNA level suggesting an altered translation.…”

Section: Discussionmentioning

confidence: 99%

Genomic Action of Sigma-1 Receptor Chaperone Relates to Neuropathic Pain

et al. 2021

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Sigma-1 receptors (Sig-1Rs) are endoplasmic reticulum (ER) chaperones implicated in neuropathic pain. Here we examine if the Sig-1R may relate to neuropathic pain at the level of dorsal root ganglia (DRG). We focus on the neuronal excitability of DRG in a “spare nerve injury” (SNI) model of neuropathic pain in rats and find that Sig-1Rs likely contribute to the genesis of DRG neuronal excitability by decreasing the protein level of voltage-gated Cav2.2 as a translational inhibitor of mRNA. Specifically, during SNI, Sig-1Rs translocate from ER to the nuclear envelope via a trafficking protein Sec61β. At the nucleus, the Sig-1R interacts with cFos and binds to the promoter of 4E-BP1, leading to an upregulation of 4E-BP1 that binds and prevents eIF4E from initiating the mRNA translation for Cav2.2. Interestingly, in Sig-1R knockout HEK cells, Cav2.2 is upregulated. In accordance with those findings, we find that intra-DRG injection of Sig-1R agonist (+)pentazocine increases frequency of action potentials via regulation of voltage-gated Ca2+ channels. Conversely, intra-DRG injection of Sig-1R antagonist BD1047 attenuates neuropathic pain. Hence, we discover that the Sig-1R chaperone causes neuropathic pain indirectly as a translational inhibitor.

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Section: Discussionmentioning

confidence: 99%

Genomic Action of Sigma-1 Receptor Chaperone Relates to Neuropathic Pain

et al. 2021

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“…На фоне вызванной формалином воспалительной боли наблюдали усиление образования иРНК и белка TASK-1 в нейронах ипсилатерального L5 дорсального ганглия, но не в спинном мозге, а образование иРНК и белка TASK-3 возрастало в обеих структурах. При вызванной наложением лигатуры на седалищный нерв нейропатической боли наблюдали снижение плотности TASK-3 каналов в нейронах ипсилатеральных L4 и L5 дорсальных ганглиев, а количество TASK-1 каналов не изменялось [12]. Таким образом, протон-чувствительные каналы семейства TASK играют определенную роль в развитии хронической воспалительной и нейропатической боли.…”

Section: хроническая нейропатическая больunclassified

Correction of disorders of neuronal homeostatic mechanisms in case of neuropsychiatric diseases as a probable direction of drug exposure

Игоревич¹,

Владимирович²,

Васильевич³

et al. 2020

Kursk Scientific and Practical Bulletin “Man and His Health”

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The improvement of drug therapy for a number of neuropsychiatric diseases requires the search for new directions of action in comparison with those currently used. Most of the drugs used affect molecular targets that modulate interstructural (interneuronal) interactions. Influencing the deeper processes of synaptic and neuronal homeostasis may be a new direction in the treatment of these diseases. This review examines the mechanisms of homeostatic plasticity of synaptic transmission and electrical excitability of neurons, which balance each other and stabilize the functioning of neurons and neural networks. The first type of homeostatic plasticity is regulated by the intracellular Ca2+ concentration and the activity of protein kinases, and the second one - by membrane density of voltage-dependent ionic channels. Analysis of literature data shows that alterations in some neuro-psychiatric diseases reveal disorders of homeostatic plasticity more often in terms of monodirectional alterations of synaptic impacts and neuronal electrical excitability. Thus, mainly in preclinical studies, it was revealed that stress-induced depressive disorders of behavior are accompanied by a unidirectional increase in pyramidal neurons of 2/3 layers of the prefrontal cortex of rodents, or a weakening in neurons of the 5th layer of synaptic drive and electrical excitability. Similar disorders of homeostatic plasticity were observed by other authors in pyramidal neurons of the dorsolateral prefrontal cortex in schizophrenia, depending on the prevalence of positive or negative symptoms. In chronic neuropathic pain, an increase in the excitability of peripheral neurons of the spinal / trigeminal ganglia, neurons of the dorsal horns, and cortical neurons and an increase in incoming synaptic influences were revealed. The observed disturbances were accompanied by changes in the density of ion channels in neuronal membranes. The peculiarities of the distribution and biophysical properties of voltage-dependent potassium channels allow us to consider them as a probable molecular target for the correction of disorders of homeostatic plasticity.

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“…Since most twopore acid sensitive K 1 (TASK) channels are impaired by cleft acidification and enhanced by cleft alkalinization (Ma et al, 2012), repeated neuronal firing would increase outward K 1 currents, lowering neuronal excitability. Although these ion channels are not broadly expressed, both TASK-1 and TASK-3 are present in the rodent spinal cord (García et al, 2019). These TASK channels play an antinociceptive role by reducing overall firing rate induced by formalin injection.…”

Section: Review Of Stawarski Et Almentioning

confidence: 99%