scholarly journals Sensory neuron–derived NaV1.7 contributes to dorsal horn neuron excitability

2020 ◽  
Vol 6 (8) ◽  
pp. eaax4568 ◽  
Author(s):  
Sascha R. A. Alles ◽  
Filipe Nascimento ◽  
Rafael Luján ◽  
Ana P. Luiz ◽  
Queensta Millet ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Dorsal Horn Neuron ◽  
Mutant Mice ◽  
Afferent Neuron ◽  
Null Mutant ◽  
Dorsal Horn Neurons ◽  
Afferent Nerves ◽  
Horn Neuron ◽  
Null Mutant Mice

Expression of the voltage-gated sodium channel NaV1.7 in sensory neurons is required for pain sensation. We examined the role of NaV1.7 in the dorsal horn of the spinal cord using an epitope-tagged NaV1.7 knock-in mouse. Immuno–electron microscopy showed the presence of NaV1.7 in dendrites of superficial dorsal horn neurons, despite the absence of mRNA. Rhizotomy of L5 afferent nerves lowered the levels of NaV1.7 in the dorsal horn. Peripheral nervous system–specific NaV1.7 null mutant mice showed central deficits, with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. NaV1.7 blocker PF05089771 diminished excitability in dorsal horn neurons but had no effect on NaV1.7 null mutant mice. These data demonstrate an unsuspected functional role of primary afferent neuron-generated NaV1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis.

scholarly journals Sensory neuron-derived Nav1.7 contributes to dorsal horn neuron excitability

2019 ◽  
Author(s):  
Sascha R.A. Alles ◽  
Filipe Nascimento ◽  
Rafael Luján ◽  
Queensta Millet ◽  
Ali Bangash ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Functional Role ◽  
Dorsal Horn Neuron ◽  
Spiking Neurons ◽  
Pain Sensation ◽  
Tonic Firing ◽  
Dorsal Horn Neurons ◽  
Immuno Electron Microscopy ◽  
Horn Neuron

SummaryExpression of the voltage-gated sodium channel Nav1.7 in sensory neurons is required for pain sensation. We examined the role of Nav1.7 in the dorsal horn of the spinal cord using an epitope-tagged knock-in mouse. Immuno-electron microscopy showed the presence of Nav1.7 in dendrites of lamina II neurons, despite the absence of mRNA. Peripheral nervous system-specific Nav1.7 KO mice showed central deficits with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. Nav1.7 blocker PF05089771 diminished excitability in dorsal horn neurons, but had no effect on Nav1.7 KO mice. These data demonstrate an unsuspected functional role of peripherally generated Nav1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis.

scholarly journals Role of RANKL (TNFSF11)-Dependent Osteopetrosis in the Dental Phenotype of Msx2 Null Mutant Mice

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e80054 ◽  
Author(s):  
Beatriz Castaneda ◽  
Yohann Simon ◽  
Didier Ferbus ◽  
Benoit Robert ◽  
Julie Chesneau ◽  
...  
Keyword(s):  
Mutant Mice ◽  
Null Mutant ◽  
Null Mutant Mice

scholarly journals Role of nNOS in Blood Pressure Regulation in eNOS Null Mutant Mice

Hypertension ◽  
1998 ◽  
Vol 32 (5) ◽  
pp. 856-861 ◽  
Author(s):  
Nobutaka Kurihara ◽  
Marcos E. Alfie ◽  
David H. Sigmon ◽  
Nour-Eddine Rhaleb ◽  
Edward G. Shesely ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Regulation ◽  
Mutant Mice ◽  
Pressure Regulation ◽  
Null Mutant ◽  
Null Mutant Mice

Role of D-serine in superficial dorsal horn neuron

PAIN RESEARCH ◽  
2011 ◽  
Vol 26 (1) ◽  
pp. 19-28
Author(s):  
Yasuhiko Kawasaki ◽  
Terumasa Nakatsuka ◽  
Mika Sasaki ◽  
Fumimasa Amaya ◽  
Tatsuro Kohno
Keyword(s):  
Dorsal Horn ◽  
Dorsal Horn Neuron ◽  
Superficial Dorsal Horn ◽  
Horn Neuron

scholarly journals Electroacupuncture reduces the evoked responses of the spinal dorsal horn neurons in ankle-sprained rats

2011 ◽  
Vol 105 (5) ◽  
pp. 2050-2057 ◽  
Author(s):  
Jae Hyo Kim ◽  
Hee Young Kim ◽  
Kyungsoon Chung ◽  
Jin Mo Chung
Keyword(s):  
Dorsal Horn ◽  
Ankle Sprain ◽  
Weight Bearing ◽  
Inhibitory Effect ◽  
Dorsal Horn Neuron ◽  
Lumbar Spinal Cord ◽  
Unit Recording ◽  
Dorsal Horn Neurons ◽  
Horn Neuron

Acupuncture is shown to be effective in producing analgesia in ankle sprain pain in humans and animals. To examine the underlying mechanisms of the acupuncture-induced analgesia, the effects of electroacupuncture (EA) on weight-bearing forces (WBR) of the affected foot and dorsal horn neuron activities were examined in a rat model of ankle sprain. Ankle sprain was induced manually by overextending ligaments of the left ankle in the rat. Dorsal horn neuron responses to ankle movements or compression were recorded from the lumbar spinal cord using an in vivo extracellular single unit recording setup 1 day after ankle sprain. EA was applied to the SI-6 acupoint on the right forelimb (contralateral to the sprained ankle) by trains of electrical pulses (10 Hz, 1-ms pulse width, 2-mA intensity) for 30 min. After EA, WBR of the sprained foot significantly recovered and dorsal horn neuron activities were significantly suppressed in ankle-sprained rats. However, EA produced no effect in normal rats. The inhibitory effect of EA on hyperactivities of dorsal horn neurons of ankle-sprained rats was blocked by the α-adrenoceptor antagonist phentolamine (5 mg/kg ip) but not by the opioid receptor antagonist naltrexone (10 mg/kg ip). These data suggest that EA-induced analgesia in ankle sprain pain is mediated mainly by suppressing dorsal horn neuron activities through α-adrenergic descending inhibitory systems at the spinal level.

scholarly journals Drug discrimination and neurochemical studies in α7 null mutant mice: tests for the role of nicotinic α7 receptors in dopamine release

2008 ◽  
Vol 203 (2) ◽  
pp. 399-410 ◽  
Author(s):  
Davide Quarta ◽  
Christopher G. Naylor ◽  
Jacques Barik ◽  
Cathy Fernandes ◽  
Susan Wonnacott ◽  
...  
Keyword(s):  
Drug Discrimination ◽  
Dopamine Release ◽  
Mutant Mice ◽  
Null Mutant ◽  
Null Mutant Mice

scholarly journals Mice with mutations in Trpm1, a gene in the locus of 15q13.3 microdeletion syndrome, display pronounced hyperactivity and decreased anxiety-like behavior

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tesshu Hori ◽  
Shohei Ikuta ◽  
Satoko Hattori ◽  
Keizo Takao ◽  
Tsuyoshi Miyakawa ◽  
...  
Keyword(s):  
Visual Impairment ◽  
Wide Spectrum ◽  
Genetic Disorder ◽  
Mutant Mice ◽  
Chromosome 15 ◽  
Microdeletion Syndrome ◽  
Visual Transduction ◽  
The Central Nervous System ◽  
Null Mutant Mice

AbstractThe 15q13.3 microdeletion syndrome is a genetic disorder characterized by a wide spectrum of psychiatric disorders that is caused by the deletion of a region containing 7 genes on chromosome 15 (MTMR10, FAN1, TRPM1, MIR211, KLF13, OTUD7A, and CHRNA7). The contribution of each gene in this syndrome has been studied using mutant mouse models, but no single mouse model recapitulates the whole spectrum of human 15q13.3 microdeletion syndrome. The behavior of Trpm1−/− mice has not been investigated in relation to 15q13.3 microdeletion syndrome due to the visual impairment in these mice, which may confound the results of behavioral tests involving vision. We were able to perform a comprehensive behavioral test battery using Trpm1 null mutant mice to investigate the role of Trpm1, which is thought to be expressed solely in the retina, in the central nervous system and to examine the relationship between TRPM1 and 15q13.3 microdeletion syndrome. Our data demonstrate that Trpm1−/− mice exhibit abnormal behaviors that may explain some phenotypes of 15q13.3 microdeletion syndrome, including reduced anxiety-like behavior, abnormal social interaction, attenuated fear memory, and the most prominent phenotype of Trpm1 mutant mice, hyperactivity. While the ON visual transduction pathway is impaired in Trpm1−/− mice, we did not detect compensatory high sensitivities for other sensory modalities. The pathway for visual impairment is the same between Trpm1−/− mice and mGluR6−/− mice, but hyperlocomotor activity has not been reported in mGluR6−/− mice. These data suggest that the phenotype of Trpm1−/− mice extends beyond that expected from visual impairment alone. Here, we provide the first evidence associating TRPM1 with impairment of cognitive function similar to that observed in phenotypes of 15q13.3 microdeletion syndrome.

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