The Genetics of Neuropathic Pain from Model Organisms to Clinical Application

Calvo, Margarita; Davies, AN; Hébert, Harry L.; Weir, Greg A.; Chesler, Elissa J.; Finnerup, Nanna Brix; Levitt, Roy C.; Smith, Blair H.; Neely, G. Gregory; Costigan, Michael; Bennett, David L.H.

doi:10.1016/j.neuron.2019.09.018

Cited by 77 publications

(63 citation statements)

References 205 publications

(251 reference statements)

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“…Here, with our platform we observed both homogeneity in behavioral responses across six genetically distinct mouse lines, as well as two outlier strains with responses that mapped outside the range of those six. A wealth of prior literature demonstrated that individual differences in responsiveness to pain in both mice and humans, are driven in part by allelic variation in genes important for pain processing [28,29]. In regards to the mouse, studies carried out twenty years ago testing pain sensitivity across 11 inbred lines using 12 behavioral read-outs, revealed that depending upon the sensory modality tested, and whether the test was performed before or after injury to the somatosensory system, genotype appeared to influence mouse pain behaviors [30].…”

Section: Discussionmentioning

confidence: 99%

A machine-vision approach for automated pain measurement at millisecond timescales

Jones

Foster

Twomey

et al. 2020

Preprint

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Section: Discussionmentioning

confidence: 99%

A machine-vision approach for automated pain measurement at millisecond timescales

Jones

Foster

Twomey

et al. 2020

Preprint

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“…Peripheral Fibers Increase of peripheral sensitivity Expression of endogenous ligands and receptors on injured nerve target Increase of NF-kB pathway activity Promote the production of leukotriene ▶fig. 1 Pathophysiology of neuropathic pain [21][22][23][24][25][26][27][28][29]. lysophosphatidic acid (LPA), gamma-aminobutyric acid (GABAergic) interneurons, nuclear factor 'kappa-light-chain-enhancer' (NF-κB).…”

Section: Dorsal Root Ganglia Increase Of Calcium Concentration and Nementioning

confidence: 99%

“…Successes include the identification of ion channel variants causing hyper-excitability and the importance of neuro-immune signaling. Recent developments encompass improved sensory phenotyping in animal models and patients, brain imaging, and electrophysiology-based pain biomarkers, the collection of large well-phenotyped population cohorts, neurons derived from patient stem cells [21].…”

Section: Pathophysiology Of Neuropathic Painmentioning

confidence: 99%

Pain and Neuropathic Pain in Rheumatic Diseases

Seifert¹,

Baerwald²

2020

Aktuelle Rheumatologie

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Pain is a challenge to rheumatologists. Not only patients with active arthritis but also patients with a good therapeutic response and even in remission complain of persistent joint pain. It has been proposed that a chronic pain stimulus may have a greater impact in a chronic inflammatory state, and the process towards a pain condition may be influenced by individual predisposition for development of chronic pain. In addition, features of peripheral pain processing may be exacerbated by inflammation, and disturbed pain processing may be a feature contributing to widespread pain. Furthermore, a neuropathic component may be part of the total pain experience of our patients. There are many different strategies of pain therapy in patients with rheumatic diseases, such as pharmacological and non- pharmacological modalities.

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“…It is generally accepted that altered somatosensory and nociceptive perception in neuropathic pain result from still incompletely understood changes at the dorsal horn circuitry [50][51][52]. Several of the suspected changes occur in second order intrinsic dorsal horn neurons.…”

Section: No Overt Changes In the Translatome Of Spinal Neurons After mentioning

confidence: 99%

Neuron Type-Specific Translatomes in Spinal Cords of Naïve and Neuropathic Mice

Gupta

Scheurer

Pelczar

et al. 2020

Preprint

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The spinal dorsal horn harbors a sophisticated and heterogeneous network of excitatory and inhibitory neurons that process peripheral signals encoding different sensory modalities. Although it has long been recognized that this network is crucial both for the separation and the integration of sensory signals of different modalities, the molecular identity of the underlying neurons and signaling mechanisms are still only partially understood. Here, we have used the translating ribosome affinity purification (TRAP) technique to map the translatomes of excitatory glutamatergic (VGLUT2 + ) and inhibitory GABA and/or glycinergic (VGAT + or Gad67 + ) neurons of the mouse spinal cord. Our analyses demonstrate that inhibitory and excitatory neurons are primarily set apart by the expression of genes encoding transcription factors or genes related to the production, release or re-uptake of their principal neurotransmitters (glutamate, GABA or glycine). Subsequent gene ontology (GO) term analyses revealed that neuropeptide signaling-related GO terms were highly enriched in the excitatory population. Eleven neuropeptide genes displayed largely non-overlapping expression patterns closely adhering to the laminar and hence also functional organization of the spinal cord grey matter, suggesting that they may serve as major determinants of modality-specific processing. Since this modality-specific processing of sensory input is severely compromised in chronic, especially neuropathic, pain, we also investigated whether peripheral nerve damage changes the neuron typespecific translatome. In summary, our results suggest that neuropeptides contribute to modalityspecific sensory processing in the spinal cord but also indicate that altered sensory encoding in neuropathic pain states occurs independent of major translatome changes in the spinal neurons.The ability to sense and discriminate different noxious and innocuous somatosensory stimuli is essential for all higher animals and humans in order to react adequately to external stimuli and internal conditions [1,2]. The spinal dorsal horn, i.e., the sensory part of the spinal cord, constitutes a key element in this process. It receives somatosensory signals from peripheral neurons and processes these signals together with other inputs descending from supraspinal sites in a complex network of inhibitory and excitatory interneurons before relaying these signals via projection neurons to supraspinal centers [3]. Projection neurons make up less than 10% of all dorsal horn neurons, while more than 90% of the neuronal population are interneurons of which, between 60 and 70% are excitatory glutamatergic neurons, and the rest is inhibitory (GABA and/or glycinergic).The spinal cord is organized in a laminar fashion, which has initially been proposed on the basis of differences in cell density and morphology between the different laminae [4, 5] but has later been shown to also reflect functional organization. This is especially reflected for example by the lamina specific innervation pattern by ...

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The Genetics of Neuropathic Pain from Model Organisms to Clinical Application

Cited by 77 publications

References 205 publications

A machine-vision approach for automated pain measurement at millisecond timescales

A machine-vision approach for automated pain measurement at millisecond timescales

Pain and Neuropathic Pain in Rheumatic Diseases

Neuron Type-Specific Translatomes in Spinal Cords of Naïve and Neuropathic Mice

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