Genetic pain loss disorders

Lischka, Annette; Laššuthová, Petra; Çakar, Arman; Record, Christopher J; Lent, Jonas Van; Baets, Jonathan; Dohrn, Maike F.; Senderek, Jan; Lampert, Angelika; Bennett, David L.H.; Wood, John N.; Timmerman, Vincent; Hornemann, Thorsten; Auer‐Grumbach, Michaela; Parman, Yeşim; Hübner, Christian A.; Elbracht, Miriam; Eggermann, Katja; Woods, C. Geoffrey; Cox, James J.; Reilly, Mary M.; Kurth, Ingo

doi:10.1038/s41572-022-00365-7

Cited by 25 publications

(42 citation statements)

References 318 publications

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“…Alterations in painful sensitivity are found in multiple clinical pictures. For narrative purposes, hereditary sensory and autonomic neuropathies (HSANs) [ 4 ], and numeric and structural chromosomal abnormalities are reported. In the former group (Mendelian disorders), nociception is altered due to a mutation in an ion channel (channelopathies), structural neuronal elements, nociception modulators, or transcription factors.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, this approach is limited by continuous updates because of the discovery of new mutations and/or the more precise identification of genotype–phenotype correlations. As Lischka et al [ 4 ] recently highlighted, a precise terminology is still lacking.…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, a heterogeneous group of genetic disorders is phenotypically characterized by increased pain threshold or pain insensitivity. Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathy (HSAN) are examples of Mendelian pain loss conditions [ 4 ], but several numeric and structural chromosomal abnormalities are also described. Clinical features encompass pain alterations combined or not with a variety of neurological manifestations, as well as symptoms affecting different organs and systems.…”

Section: Introductionmentioning

confidence: 99%

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Pathophysiology of Nociception and Rare Genetic Disorders with Increased Pain Threshold or Pain Insensitivity

Cascella

Muzio²,

Monaco

et al. 2022

Pathophysiology

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Pain and nociception are different phenomena. Nociception is the result of complex activity in sensory pathways. On the other hand, pain is the effect of interactions between nociceptive processes, and cognition, emotions, as well as the social context of the individual. Alterations in the nociceptive route can have different genesis and affect the entire sensorial process. Genetic problems in nociception, clinically characterized by reduced or absent pain sensitivity, compose an important chapter within pain medicine. This chapter encompasses a wide range of very rare diseases. Several genes have been identified. These genes encode the Nav channels 1.7 and 1.9 (SCN9A, and SCN11A genes, respectively), NGFβ and its receptor tyrosine receptor kinase A, as well as the transcription factor PRDM12, and autophagy controllers (TECPR2). Monogenic disorders provoke hereditary sensory and autonomic neuropathies. Their clinical pictures are extremely variable, and a precise classification has yet to be established. Additionally, pain insensitivity is described in diverse numerical and structural chromosomal abnormalities, such as Angelman syndrome, Prader Willy syndrome, Chromosome 15q duplication syndrome, and Chromosome 4 interstitial deletion. Studying these conditions could be a practical strategy to better understand the mechanisms of nociception and investigate potential therapeutic targets against pain.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pathophysiology of Nociception and Rare Genetic Disorders with Increased Pain Threshold or Pain Insensitivity

Cascella

Muzio²,

Monaco

et al. 2022

Pathophysiology

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“…Pain is a sensory modality used to detect potential and real tissue damage, providing a survival advantage 1,2 . Genetic pain loss disorders are classified as congenital insensitivity to pain (CIP) or hereditary sensory and autonomic neuropathy (HSAN) 2,3 .…”

Section: Introductionmentioning

confidence: 99%

“…In all cases of CIP or HSAN, the consistent feature is decreased pain perception and resulting injuries 2,3 . In humans, seven forms of CIP and eight forms of HSAN have been described based on phenotype, and genetic variants in at least 26 genes have been reported 2,3 …”

Section: Introductionmentioning

confidence: 99%

SCN9A variant in a family of mixed breed dogs with congenital insensitivity to pain

Quintana

Christen

Faller

et al. 2023

Veterinary Internal Medicne

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Background: Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSANs) are a rare group of genetic disorders causing inability to feel pain. Three different associated variants have been identified in dogs: 1 in Border Collies, 1 in mixed breed dogs, and 1 in Spaniels and Pointers.Objectives: To clinically and genetically characterize CIP in a family of mixed breed dogs.Animals: Two mixed breed dogs from the same litter were independently presented:1 for evaluation of painless fractures, and the other for chronic thermal skin injuries.Methods: Physical, neurological, and histopathological evaluations were performed.Whole genome sequencing of 1 affected dog was used to identify homozygous protein-changing variants that were not present in 926 control genomes from diverse dog breeds.Results: Physical and neurological examinations showed the absence of superficial and deep pain perception in the entire body. Histopathological evaluations of the brain, spinal cord and sensory ganglia were normal. Whole genome sequencing identified a homozygous missense variant in SCN9A, XM_038584713.1:c.2761C>T or XP_038440641.1:(p.Arg921Cys). Both affected dogs were homozygous for the mutant allele, which was not detected in 926 dogs of different breeds. Conclusions and Clinical Importance:We confirmed the diagnosis of CIP in a family of mixed breed dogs and identified a likely pathogenic variant in the SCN9A gene.The clinical signs observed in these dogs mimic those reported in humans with pathogenic SCN9A variants causing CIP. This report is the first of a spontaneous pathogenic SCN9A variant in domestic animals.

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Toward the Next Generation of Neural Iontronic Interfaces

Forró

Musall

Montes³

et al. 2023

Adv Healthcare Materials

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Neural interfaces are evolving at a rapid pace owing to advances in material science and fabrication, reduced cost of scalable complementary metal oxide semiconductor (CMOS) technologies, and highly interdisciplinary teams of researchers and engineers that span a large range from basic to applied and clinical sciences. This study outlines currently established technologies, defined as instruments and biological study systems that are routinely used in neuroscientific research. After identifying the shortcomings of current technologies, such as a lack of biocompatibility, topological optimization, low bandwidth, and lack of transparency, it maps out promising directions along which progress should be made to achieve the next generation of symbiotic and intelligent neural interfaces. Lastly, it proposes novel applications that can be achieved by these developments, ranging from the understanding and reproduction of synaptic learning to live‐long multimodal measurements to monitor and treat various neuronal disorders.

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Genetic pain loss disorders

Cited by 25 publications

References 318 publications

Pathophysiology of Nociception and Rare Genetic Disorders with Increased Pain Threshold or Pain Insensitivity

Pathophysiology of Nociception and Rare Genetic Disorders with Increased Pain Threshold or Pain Insensitivity

SCN9A variant in a family of mixed breed dogs with congenital insensitivity to pain

Toward the Next Generation of Neural Iontronic Interfaces

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