Identification of differentially expressed proteins in the spinal cord of neuropathic pain models with PKCgamma silence by proteomic analysis

Zou, Wangyuan; Zhan, Xianquan; Li, Maoyu; Song, Zongbin; Liu, Chang; Peng, Fang; Guo, Qulian

doi:10.1016/j.brainres.2011.12.046

Cited by 28 publications

(30 citation statements)

References 55 publications

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“…Fibronectin has been shown to upregulate spinal microglial cell expression of P2X 4 R 59 . After peripheral nerve injury, HSP60 is upregulated in the spinal cord and intrathecal HSP90 inhibition reverses allodynia 75,76 .…”

Section: The Neuroimmune Interface In Pathological Painmentioning

confidence: 99%

Pathological pain and the neuroimmune interface

et al. 2014

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Reciprocal signalling between immunocompetent cells in the central nervous system (CNS) has emerged as a key phenomenon underpinning pathological and chronic pain mechanisms. Neuronal excitability can be powerfully enhanced both by classical neurotransmitters derived from neurons, and by immune mediators released from CNS-resident microglia and astrocytes, and from infiltrating cells such as T cells. In this Review, we discuss the current understanding of the contribution of central immune mechanisms to pathological pain, and how the heterogeneous immune functions of different cells in the CNS could be harnessed to develop new therapeutics for pain control. Given the prevalence of chronic pain and the incomplete efficacy of current drugs — which focus on suppressing aberrant neuronal activity — new strategies to manipulate neuroimmune pain transmission hold considerable promise.

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Section: The Neuroimmune Interface In Pathological Painmentioning

confidence: 99%

Pathological pain and the neuroimmune interface

et al. 2014

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“…Piezo2 and TRPA1 channels (supplemental Table S2). Further comparison with published proteomes of neuromas, sciatic nerve, DRG, and spinal cord (harboring presynaptic terminals of DRG neurons) demonstrates, that our spectral library constitutes the largest compendium of DRG proteins reported to date (9,10,(12)(13)(14)65). The generated resource is publically available in PeptideAtlas (66) and constitutes an optimized resort for unbiased, consistent and highly accurate protein quantification in future DIA-MS experiments of any mouse sample of interest.…”

Section: Overview Of Our Integrated Workflow: From Murine Chronicmentioning

confidence: 99%

Standardized Profiling of The Membrane-Enriched Proteome of Mouse Dorsal Root Ganglia (DRG) Provides Novel Insights Into Chronic Pain

Rouwette

Sondermann

Avenali

et al. 2016

Molecular & Cellular Proteomics

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Chronic pain is a complex disease with limited treatment options. Several profiling efforts have been employed with the aim to dissect its molecular underpinnings. However, generated results are often inconsistent and nonoverlapping, which is largely because of inherent technical constraints. Emerging data-independent acquisition (DIA)-mass spectrometry (MS) has the potential to provide unbiased, reproducible and quantitative proteome mapsa prerequisite for standardization among experiments. Here, we designed a DIA-based proteomics workflow to profile changes in the abundance of dorsal root ganglia (DRG) proteins in two mouse models of chronic pain, inflammatory and neuropathic. We generated a DRG-specific spectral library containing 3067 DRG proteins, which enables their standardized quantification by means of DIA-MS in any laboratory. Using this resource, we profiled 2526 DRG proteins in each biological replicate of both chronic pain models and respective controls with unprecedented reproducibility. We detected numerous differentially regulated proteins, the majority of which exhibited pain model-specificity. Our approach recapitulates known biology and discovers dozens of proteins that have not been characterized in the somatosensory system before. Functional validation experiments and analysis of mouse pain behaviors demonstrate that indeed meaningful protein alterations were discovered. These results illustrate how the application of DIA-MS can open new avenues to achieve the long-awaited standardization in the molecular dissection of pathologies of the somatosensory system.

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“…Proteomic analysis in neuropathic pain models reveal an up-regulation of glutamate dehydrogenase 1 (GDH) which  is a key enzyme in the regulation of glutamate metabolism [21, 22]. …”

Section: Discussionmentioning

confidence: 99%

“…It is also up-regulated in hyper-excitable neuromas in rodent saphenous nerves [23]. Fructose-bisphosphate aldolase C is downregulated in PKC gamma knockdown rats [21]. Intrathecal morphine therapy also alters the expression of these enzymes.…”

Section: Discussionmentioning

confidence: 99%

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The Proteomics of Intrathecal Analgesic agents for Chronic Pain

Moore¹,

McCrory

2017

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Chronic pain remains a challenging clinical problem with a growing socio-economic burden for the state. Its prevalence is high and many of the patients are of work age. Our knowledge regarding the pathophysiology of chronic pain is poor. The consensus view is that the central nervous system plays a key role in the persistence of pain after an initiating event has long ceased. However the specifics of this biological response to an initiating event remains unclear. There is a growing body of evidence to support the concept that a central neuroimmune response is initiated and a number of small peptides have been implicated in this process following cerebrospinal fluid analysis in patients with chronic pain. This central biosynthetic peptide response leads to a process called central sensitization. Therapy is aimed at modulating and even inhibiting this response. However current pharmacological therapeutic options are limited in efficacy with significant deleterious side effect profiles. Proteomic studies extend single molecule analysis by identifying the components of biological networks and pathways and defining their interactions. This tool offers the potential to provide a molecular overview of the biological processes involved in chronic pain. It will also facilitate examination of gene-drug interactions. This technique offers a mechanism of defining the central biological responses that result in chronic pain and this information may facilitate the development of better therapies.

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Identification of differentially expressed proteins in the spinal cord of neuropathic pain models with PKCgamma silence by proteomic analysis

Cited by 28 publications

References 55 publications

Pathological pain and the neuroimmune interface

Pathological pain and the neuroimmune interface

Standardized Profiling of The Membrane-Enriched Proteome of Mouse Dorsal Root Ganglia (DRG) Provides Novel Insights Into Chronic Pain

The Proteomics of Intrathecal Analgesic agents for Chronic Pain

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