Overexpressed NaV1.7 Channels Confer Hyperexcitability to in vitro Trigeminal Sensory Neurons of CaV2.1 Mutant Hemiplegic Migraine Mice

Mehboob, Riffat; Marchenkova, Anna; Maagdenberg, Arn M. J. M. van den; Nistri, Andrea

doi:10.3389/fncel.2021.640709

Cited by 4 publications

(2 citation statements)

References 88 publications

(168 reference statements)

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“…Via cGMP-dependent intracellular pathways, BNP constitutively limits the activity of P2X3 receptors, a process that is largely depressed in the FHM1 phenotype [ 120 ]. In addition, FHM1 mice show upregulation of the Na v 1.7 subtype of voltage gated sodium channel [ 121 ] that contributes to their enhanced excitability.…”

Section: Introductionmentioning

confidence: 99%

Role of ATP in migraine mechanisms: focus on P2X3 receptors

Giniatullin

Nistri

2023

J Headache Pain

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Migraine is a major health burden worldwide with complex pathophysiology and multifarious underlying mechanisms. One poorly understood issue concerns the early steps in the generation of migraine pain. To elucidate the basic process of migraine pain further, it seems useful to consider key molecular players that may operate synergistically to evoke headache. While the neuropeptide CGRP is an important contributor, we propose that extracellular ATP (that generally plays a powerful nociceptive role) is also a major component of migraine headache, acting in concert with CGRP to stimulate trigeminal nociceptive neurons. The aim of the present focused review is to highlight the role of ATP activating its P2X3 membrane receptors selectively expressed by sensory neurons including their nerve fiber terminals in the meninges. Specifically, we present data on the homeostasis of ATP and related purines in the trigeminovascular system and in the CNS; the basic properties of ATP signalling at peripheral and central nerve terminals; the characteristics of P2X3 and related receptors in trigeminal neurons; the critical speed and persistence of P2X3 receptor activity; their cohabitation at the so-called meningeal neuro-immune synapse; the identity of certain endogenous agents cooperating with ATP to induce neuronal sensitization in the trigeminal sensory system; the role of P2X3 receptors in familial type migraine; the current state of P2X3 receptor antagonists and their pharmacological perspectives in migraine. It is proposed that the unique kinetic properties of P2X3 receptors activated by ATP offer an interesting translational value to stimulate future studies for innovative treatments of migraine pain.

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Section: Introductionmentioning

confidence: 99%

Role of ATP in migraine mechanisms: focus on P2X3 receptors

Giniatullin

Nistri

2023

J Headache Pain

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“…epilepsy and chronic pain. The role of these channels in physiological and pathological pathways related to autism, migraine, multiple sclerosis, cancers and immunological disorders has also been known (1). VGSCs increase the action potentials in neurons, monocytes, glial cells and other excitable cells (2).…”

Section: Introductionmentioning

confidence: 99%

The Expression of Sodium Channel Alpha Subunit (Nav1.7) Receptors in Intracranial Meningioma and Its Comparison to Urothelial, Prostate and Ovarian Cancers

Mehboob¹,

Kurdi²,

Baeesa³

et al. 2021

PJMHS

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Nav1.7/SCN9A is a voltage gated sodium ion channel (VGSC), expressed by nociceptive neurons. Its role in pain mechanism was well- established but its involvement in the carcinogenic pathways is still under investigation. We aimed to explore the expression of Nav1.7/ SCN9A receptors in intracranial meningiomas and compare it with urothelial, prostate, and ovarian cancers. Methods: Ten paraffin embedded tissue samples of brain meningioma and 5 cases each of bladder, prostate and ovarian carcinomas were utilized. Immunohistochemistry (IHC) was performed using anti-SCN9A antibody. Cases were scored based on the intensity of expression and number of positive tumour cells. A score of (+3) indicated highest intensity, (+2) as moderate and (+1) as weak intensity. Similarly, 50-100% expression in cells was labelled as (+3), moderate, 30-50% as (+2) and 10-20% as weak or (+1) expression, and (0) as negative. Results: Nine cases of meningioma were in grade I and single case was grade III. The nine grade I meningioma were negative for SCN9/Nav1.7 expression while the single grade III case was positive. Tumour cells in urothelial, prostate, and ovarian carcinomas were all strongly positive for SCN9/Nav1.7, having intensity expression as (+3). Conclusions: This study suggests an emerging role of Nav1.7/SCN9A receptor expression in urothelial, prostate, and ovarian cancers as well as grade III meningiomas compared to grade I meningioma. This clarifies that Nav1.7/SCN9A has a possible role in carcinogenesis of most body tumours. Key Words: Nav1.7, sodium channels, Ion channels, Channelopathy, meningioma, carcinoma

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