Botulinum toxin type A reduces the expression of transient receptor potential melastatin 3 and transient receptor potential vanilloid type 4 in the trigeminal subnucleus caudalis of a rat model of trigeminal neuralgia

Neuroreport ◽  
2019 ◽  
Vol 30 (10) ◽  
pp. 735-740 ◽  
Author(s):  
Yi Zhang ◽  
Qiuyang Su ◽  
Yajun Lian ◽  
Yuan Chen
Keyword(s):  
Botulinum Toxin ◽  
Trigeminal Neuralgia ◽  
Transient Receptor Potential ◽  
Botulinum Toxin Type A ◽  
Receptor Potential ◽  
Botulinum Toxin Type ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
Trigeminal Subnucleus Caudalis

scholarly journals Trigeminal Neuralgia TRPM8 Mutation

2021 ◽  
Vol 7 (1) ◽  
pp. e550
Author(s):  
Roberta Gualdani ◽  
Jun-Hui Yuan ◽  
Philip R. Effraim ◽  
Giulia Di Stefano ◽  
Andrea Truini ◽  
...  
Keyword(s):  
Trigeminal Neuralgia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Nonselective Cation Channel ◽  
Patch Clamp Recording ◽  
Mutant Channel ◽  
Whole Cell Patch Clamp ◽  
Transient Receptor Potential Melastatin ◽  
Intracellular Ca ◽  
Transient Receptor

ObjectiveTo assess the functional effects of a variant, c.89 G > A (p.Arg30Gln), in the transient receptor potential melastatin 8 (TRPM8) cold-sensing, nonselective cation channel, which we have previously identified in a patient with familial trigeminal neuralgia.MethodsWe carried out Ca2+ imaging and whole-cell patch-clamp recording.ResultsThe TRPM8 mutation enhances channel activation, increases basal current amplitude and intracellular [Ca2+] in cells carrying the mutant channel, and enhances the response to menthol.ConclusionsWe propose that Arg30Gln confers gain-of-function attributes on TRPM8, which contribute to pathogenesis of trigeminal neuralgia in patients carrying this mutation.

scholarly journals TRPM4 is required for calcium oscillations downstream from the stretch-activated TRPV4 channel

2021 ◽  
Author(s):  
Oleg Yarishkin ◽  
Tam T. Phuong ◽  
Felix Vazquez-Chona ◽  
Jacques A Bertrand ◽  
Sarah Redmon ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Membrane Surface ◽  
Receptor Potential ◽  
Calcium Oscillations ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
Insight Into

Transduction of mechanical information is influenced by physical, chemical and thermal cues but the molecular mechanisms through which transducer activation shapes temporal signaling remain underexplored. In the present study, electrophysiology, histochemistry and functional imaging were combined with gene silencing and heterologous expression to gain insight into calcium signaling downstream from TRPV4 (Transient Receptor Potential Vanilloid 4), a stretch-activated nonselective cation channel. We show that trabecular meshwork (TM) cells, which employ mechanotransduction to actively regulate intraocular pressure, respond to the TRPV4 agonist GSK1016790A with fluctuations in intracellular Ca2+ concentration ([Ca2+]i) and an increase in [Na+]i. [Ca2+]i oscillations coincided with a monovalent cation current that was suppressed by BAPTA, Ruthenium Red and 9-phenanthrol, an inhibitor of TRPM4 (Transient Receptor Potential Melastatin 4) channels. Accordingly, TM cells expressed TRPM4 mRNA, protein at the expected 130-150 kDa and showed punctate TRPM4 immunoreactivity at the membrane surface. Genetic silencing of TRPM4 antagonized TRPV4-evoked oscillatory signaling whereas TRPV4 and TRPM4 co-expression in HEK-293 cells reconstituted the oscillations. Membrane potential recordings indicated that TRPM4-dependent oscillations required release of Ca2+ from internal stores. 9-phenanthrol did not affect the outflow facility in mouse eyes. Collectively, our results show that TRPV4 activity initiates dynamic calcium signaling in TM cells by stimulating TRPM4 channels and intracellular Ca2+ release. These findings provide insight into the complexity of membrane-cytosolic interactions during TRPV4 signaling and may foster strategies to promote homeostatic regulation and counter pathological remodeling within the conventional outflow pathway of the mammalian eye.

Heartburn Sensation in Non-Erosive Reflux Disease: Pattern of Superficial Sensory Nerves Expressing TRPV1 and Epithelial Cells Expressing ASIC3 Receptors

2021 ◽  
Author(s):  
Ahsen Ustaoglu ◽  
Akinari Sawada ◽  
Chung Lee ◽  
Wei-Yi Lei ◽  
Chien-Lin Chen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Reflux Disease ◽  
Transient Receptor Potential ◽  
Sensory Nerve ◽  
Receptor Potential ◽  
Sensory Nerves ◽  
Transient Receptor Potential Vanilloid ◽  
Esophageal Mucosa ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

The underlying causes of heartburn, characteristic symptom of gastro-esophageal reflux disease(GERD), remain incompletely understood. Superficial afferent innervation of the esophageal mucosa in nonerosive reflux disease(NERD) may drive nociceptive reflux perception, but its acid-sensing role has not yet been established. Transient receptor potential vanilloid subfamily member-1(TRPV1), transient receptor potential Melastatin 8(TRPM8), and acid sensing ion channel 3(ASIC3) are regulators of sensory nerve activity and could be important reflux-sensing receptors within the esophageal mucosa. We characterised TRPV1, TRPM8, and ASIC3 expression in esophageal mucosa of GERD patients. We studied 10 NERD, 10 erosive reflux disease(ERD), 7 functional heartburn(FH), and 8 Barrett's esophagus(BE) patients. Biopsies obtained from the distal esophageal mucosa were co-stained with TRPV1, TRPM8, or ASIC3, and CGRP, CD45, or E-cadherin. RNA expression of TRPV1, TRPM8, and ASIC3 was assessed using qPCR. NERD patients had significantly increased expression of TRPV1 on superficial sensory nerves compared to ERD (p=0.028) or BE (p=0.017). Deep intrapapillary nerve endings did not express TRPV1 in all phenotypes studied. ASIC3 was exclusively expressed on epithelial cells most significantly in NERD and ERD patients (p=<0.0001). TRPM8 was expressed on submucosal CD45+ leukocytes. Superficial localisation of TRPV1-immunoreactive nerves in NERD, and increased ASIC3 co-expression on epithelial cells in NERD and ERD suggests a mechanism for heartburn sensation. Esophageal epithelial cells may play a sensory role in acid reflux perception and act interdependently with TRPV1-expressing mucosal nerves to augment hypersensitivity in NERD patients, raising the enticing possibility of topical antagonists for these ion channels as a therapeutic option.

Synergic Effect of Botulinum Toxin Type-A and Triamcinolone Alleviates Scar Pruritus By Modulating Epidermal Hyperinnervation: A Preliminary Report

2021 ◽  
Author(s):  
Shu-Hung Huang ◽  
Kuo-Wei Wu ◽  
Jing-Jou Lo ◽  
Sheng-Hua Wu
Keyword(s):  
Botulinum Toxin ◽  
Clinical Efficacy ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Botulinum Toxin Type A ◽  
Type A ◽  
Botulinum Toxin Type ◽  
Nerve Fibers ◽  
Therapeutic Interventions ◽  
Transient Receptor Potential Vanilloid

Abstract Background Patients often experience scar-related pruritus, which negatively affects quality of life. Triamcinolone acetonide (TAC) is widely used to treat pathological scars, and botulinum toxin type-A (BTX-A) reportedly improves scarring and associated discomfort. Objectives To investigate the clinical efficacy of the combined TAC and BTX-A (TAC/BTX-A) in reducing scar itch and their potential mechanisms via animal model. Methods In a clinical study, each scar on a patient was divided into 2 equal parts, with one part receiving TAC/BTX-A and the other TAC alone. Therapeutic interventions were administered over 3 sessions, each 4 weeks apart. Itch intensity was measured using visual analogue scale before each therapeutic intervention (V1, V2, V3) and 4 weeks after the last intervention (V4). In a rat model, rats were allocated into 5 groups: control, untreated burn, TAC, BTX-A, and TAC/BTX-A groups. We evaluated alloknesis in the right hind paw and analyzed possible molecular mechanisms. Results In humans, TAC/BTX-A significantly reduced scar itch compared with TAC alone at V4 (p = 0.04). In rats, post-burn itch was mitigated at 4 weeks after treatment with TAC, BTX-A, and TAC/BTX-A (p = 0.03, p = 0.0054, and p = 0.0053, respectively). TAC/BTX-A significantly decreased the density of intraepidermal nerve fibers post-burn relative to the untreated burn (p = 0.0008). TAC/BTX-A downregulated the expressions of nerve growth factor (NGF) and protein transient receptor potential vanilloid subtype 1 (TRPV1). Conclusions TAC/BTX-A therapy exhibited enhanced and sustained clinical efficacy in relieving scar itch, possibly via modulating epidermal innervation and TRPV1 expression.

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