Chronicling changes in the somatosensory neurons after peripheral nerve injury.

Abstract:

:Current drug discovery efforts focus on identifying lead compounds acting on a molecular target associated with an established pathological state. Concerted molecular changes that occur in specific cell types during disease progression have generally not been identified. Here, we used constellation pharmacology to investigate rat dorsal root ganglion neurons using two models of peripheral nerve injury: chronic constriction injury (CCI) and spinal nerve ligation (SNL). In these well-established models of neuropathic pain, we show that the onset of chronic pain is accompanied by a dramatic, previously unreported increase in the number of bradykinin-responsive neurons, with larger increases observed after SNL relative to CCI. To define the neurons with altered expression, we charted the temporal course of molecular changes following 1, 3, 6, and 14 d after SNL injury and demonstrated that specific molecular changes have different time courses during the progression to a pain state. In particular, ATP receptors up-regulated on day 1 postinjury, whereas the increase in bradykinin receptors was gradual after day 3 postinjury. We specifically tracked changes in two subsets of neurons: peptidergic and nonpeptidergic nociceptors. Significant increases occurred in ATP responses in nAChR-expressing isolectin B4+ nonpeptidergic neurons 1 d postinjury, whereas peptidergic neurons did not display any significant change. We propose that remodeling of ion channels and receptors occurs in a concerted and cell-specific manner, resulting in the appearance of bradykinin-responsive neuronal subclasses that are relevant to chronic pain.

authors

Raghuraman S,Xie JY,Giacobassi MJ,Tun JO,Chase K,Lu D,Teichert RW,Porreca F,Olivera BM

doi

10.1073/pnas.1922618117

subject

Has Abstract

pub_date

2020-10-20 00:00:00

pages

26414-26421

issue

42

eissn

0027-8424

issn

1091-6490

pii

1922618117

journal_volume

117

pub_type

杂志文章
  • Aberrantly elevated microRNA-34a in obesity attenuates hepatic responses to FGF19 by targeting a membrane coreceptor β-Klotho.

    abstract::MicroRNA-34a (miR-34a) is the most highly elevated hepatic miR in obese mice and is also substantially elevated in patients who have steatosis, but its role in obesity and metabolic dysfunction remains unclear. After a meal, FGF19 is secreted from the ileum; binds to a hepatic membrane receptor complex, FGF19 receptor...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1205951109

    authors: Fu T,Choi SE,Kim DH,Seok S,Suino-Powell KM,Xu HE,Kemper JK

    更新日期:2012-10-02 00:00:00

  • Altered chlorplast ribosomal proteins associated with erythromycin-resistant mutants in two genetic systems of Chlamydomonas reinhardi.

    abstract::The phenotype of several erythromycin-resistant mutants of Chlamydomonas reinhardi was further characterized in terms of the electrophoretic properties of their chloroplast ribosomal proteins. In mutant ery-M2d a single protein of the large (52 S) subunit has altered properties, which probably result from a change in ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.12.3779

    authors: Mets L,Bogorad L

    更新日期:1972-12-01 00:00:00

  • The energy of substituted ethanes. Asymmetry orbitals.

    abstract::The leading terms in the energy of a general substituted ethane are derived in explicit form as a function of the torsional angle theta, the substituent electronegativities, and their mutual overlaps. The energy is found to be the sum of all four overlaps between pairs of asymmetry orbitals, and satisfies the requisit...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.70.2.531

    authors: Salem L,Hoffmann R,Otto P

    更新日期:1973-02-01 00:00:00

  • Serum amyloid A forms stable oligomers that disrupt vesicles at lysosomal pH and contribute to the pathogenesis of reactive amyloidosis.

    abstract::Serum amyloid A (SAA) is an acute-phase plasma protein that functions in innate immunity and lipid homeostasis. SAA is a protein precursor of reactive AA amyloidosis, the major complication of chronic inflammation and one of the most common human systemic amyloid diseases worldwide. Most circulating SAA is protected f...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1707120114

    authors: Jayaraman S,Gantz DL,Haupt C,Gursky O

    更新日期:2017-08-08 00:00:00

  • Magnetic microposts as an approach to apply forces to living cells.

    abstract::Cells respond to mechanical forces whether applied externally or generated internally via the cytoskeleton. To study the cellular response to forces separately, we applied external forces to cells via microfabricated magnetic posts containing cobalt nanowires interspersed among an array of elastomeric posts, which act...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0611613104

    authors: Sniadecki NJ,Anguelouch A,Yang MT,Lamb CM,Liu Z,Kirschner SB,Liu Y,Reich DH,Chen CS

    更新日期:2007-09-11 00:00:00

  • Lipophosphoglycan of Leishmania major that vaccinates against cutaneous leishmaniasis contains an alkylglycerophosphoinositol lipid anchor.

    abstract::The major cell surface glycoconjugate of Leishmania major, a putative parasite receptor for macrophages, is a lipophosphoglycan containing 81.6% (wt/wt) carbohydrate, 17.0% (wt/wt) phosphate, and 1.4% (wt/wt) lipid. It has been purified to homogeneity by hydrophobic chromatography and consists of a polydisperse family...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.24.8941

    authors: McConville MJ,Bacic A,Mitchell GF,Handman E

    更新日期:1987-12-01 00:00:00

  • Alloreactive immune responses of transgenic mice expressing a foreign transplantation antigen in a soluble form.

    abstract::Transfection of cells with the H-2Kk gene lacking the transmembrane and cytoplasmic segments resulted in secretion of the H-2Kk protein, as determined by immunoprecipitation with monoclonal anti-H-2Kk antibodies. Transgenic (H-2b X H-2d)F1 mice were established carrying integrated copies of the modified H-2Kk gene. Ex...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.7.2269

    authors: Arnold B,Dill O,Küblbeck G,Jatsch L,Simon MM,Tucker J,Hämmerling GJ

    更新日期:1988-04-01 00:00:00

  • Inhibition of the K+ channel KCa3.1 ameliorates T cell-mediated colitis.

    abstract::The calcium-activated K(+) channel KCa3.1 plays an important role in T lymphocyte Ca(2+) signaling by helping to maintain a negative membrane potential, which provides an electrochemical gradient to drive Ca(2+) influx. To assess the role of KCa3.1 channels in lymphocyte activation in vivo, we studied T cell function ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0910133107

    authors: Di L,Srivastava S,Zhdanova O,Ding Y,Li Z,Wulff H,Lafaille M,Skolnik EY

    更新日期:2010-01-26 00:00:00

  • Human cytomegalovirus pUL37x1 induces the release of endoplasmic reticulum calcium stores.

    abstract::The human CMV UL37x1-encoded protein, also known as the viral mitochondria-localized inhibitor of apoptosis, traffics to the endoplasmic reticulum and mitochondria of infected cells. It induces the fragmentation of mitochondria and blocks apoptosis. We demonstrate that UL37x1 protein mobilizes Ca(2+) from the endoplas...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0609353103

    authors: Sharon-Friling R,Goodhouse J,Colberg-Poley AM,Shenk T

    更新日期:2006-12-12 00:00:00

  • Complementation of a red-light-indifferent cyanobacterial mutant.

    abstract::Many cyanobacteria alter their phycobilisome composition in response to changes in light wavelength in a process termed complementary chromatic adaptation. Mutant strains FdR1 and FdR2 of the filamentous cyanobacterium Fremyella diplosiphon are characterized by aberrant chromatic adaptation. Instead of adjusting to di...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.20.9415

    authors: Chiang GG,Schaefer MR,Grossman AR

    更新日期:1992-10-15 00:00:00

  • Solution to the problem of the poor cyclic fatigue resistance of bulk metallic glasses.

    abstract::The recent development of metallic glass-matrix composites represents a particular milestone in engineering materials for structural applications owing to their remarkable combination of strength and toughness. However, metallic glasses are highly susceptible to cyclic fatigue damage, and previous attempts to solve th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0900740106

    authors: Launey ME,Hofmann DC,Johnson WL,Ritchie RO

    更新日期:2009-03-31 00:00:00

  • Members of the HRT family of basic helix-loop-helix proteins act as transcriptional repressors downstream of Notch signaling.

    abstract::The Hairy-related transcription-factor (HRT) genes encode three related basic helix-loop-helix transcription factors that show sequence similarity to the Hairy and Enhancer of split family of transcriptional repressors. HRT proteins are expressed in specific regions of the developing heart, vasculature, pharyngeal arc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.250485597

    authors: Nakagawa O,McFadden DG,Nakagawa M,Yanagisawa H,Hu T,Srivastava D,Olson EN

    更新日期:2000-12-05 00:00:00

  • Structural basis for MTR4-ZCCHC8 interactions that stimulate the MTR4 helicase in the nuclear exosome-targeting complex.

    abstract::The nuclear exosome-targeting (NEXT) complex functions as an RNA exosome cofactor and is involved in surveillance and turnover of aberrant transcripts and noncoding RNAs. NEXT is a ternary complex composed of the RNA-binding protein RBM7, the scaffold zinc-knuckle protein ZCCHC8, and the helicase MTR4. While RNA inter...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1803530115

    authors: Puno MR,Lima CD

    更新日期:2018-06-12 00:00:00

  • DNA looping-dependent autorepression of LEE1 P1 promoters by Ler in enteropathogenic Escherichia coli (EPEC).

    abstract::Ler, a homolog of H-NS in enteropathogenic Escherichia coli (EPEC), plays a critical role in the expression of virulence genes encoded by the pathogenic island, locus of enterocyte effacement (LEE). Although Ler acts as an antisilencer of multiple LEE operons by alleviating H-NS-mediated silencing, it represses its ow...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1322033111

    authors: Bhat A,Shin M,Jeong JH,Kim HJ,Lim HJ,Rhee JH,Paik SY,Takeyasu K,Tobe T,Yen H,Lee G,Choy HE

    更新日期:2014-06-24 00:00:00

  • Human CUL1 forms an evolutionarily conserved ubiquitin ligase complex (SCF) with SKP1 and an F-box protein.

    abstract::The SCF ubiquitin ligase complex of budding yeast triggers DNA replication by catalyzing ubiquitination of the S phase cyclin-dependent kinase inhibitor SIC1. SCF is composed of three proteins-ySKP1, CDC53 (Cullin), and the F-box protein CDC4-that are conserved from yeast to humans. As part of an effort to identify co...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.13.7451

    authors: Lyapina SA,Correll CC,Kipreos ET,Deshaies RJ

    更新日期:1998-06-23 00:00:00

  • Lipoprotein lipase enhances the binding of chylomicrons to low density lipoprotein receptor-related protein.

    abstract::Chylomicron catabolism is known to be initiated by the enzyme lipoprotein lipase (triacylglycero-protein acylhydrolase, EC 3.1.1.34). Chylomicron remnants, produced by lipolysis, are rapidly taken up by the liver via an apolipoprotein E (apoE)-mediated, receptor-dependent process. The low density lipoprotein (LDL) rec...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.19.8342

    authors: Beisiegel U,Weber W,Bengtsson-Olivecrona G

    更新日期:1991-10-01 00:00:00

  • Latitudinal difference in biodiversity caused by higher tropical rate of increase.

    abstract::Tropical diversity has generally exceeded temperate diversity in the present and at points in the past, but whether measured differences have remained relatively constant through time has been unknown. Here we examine tropical vs. temperate diversities from the Neogene to Recent using the within-habitat diversity meas...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.122241499

    authors: Buzas MA,Collins LS,Culver SJ

    更新日期:2002-06-11 00:00:00

  • Increased drought severity tracks warming in the United States' largest river basin.

    abstract::Across the Upper Missouri River Basin, the recent drought of 2000 to 2010, known as the "turn-of-the-century drought," was likely more severe than any in the instrumental record including the Dust Bowl drought. However, until now, adequate proxy records needed to better understand this event with regard to long-term v...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1916208117

    authors: Martin JT,Pederson GT,Woodhouse CA,Cook ER,McCabe GJ,Anchukaitis KJ,Wise EK,Erger PJ,Dolan L,McGuire M,Gangopadhyay S,Chase KJ,Littell JS,Gray ST,St George S,Friedman JM,Sauchyn DJ,St-Jacques JM,King J

    更新日期:2020-05-26 00:00:00

  • An uncorrelated relaxed-clock analysis suggests an earlier origin for flowering plants.

    abstract::We present molecular dating analyses for land plants that incorporate 33 fossil calibrations, permit rates of molecular evolution to be uncorrelated across the tree, and take into account uncertainties in phylogenetic relationships and the fossil record. We attached a prior probability to each fossil-based minimum age...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.1001225107

    authors: Smith SA,Beaulieu JM,Donoghue MJ

    更新日期:2010-03-30 00:00:00

  • Structure of decay-accelerating factor bound to echovirus 7: a virus-receptor complex.

    abstract::Echoviruses are enteroviruses that belong to Picornaviridae. Many echoviruses use decay-accelerating factor (DAF) as their cellular receptor. DAF is a glycosylphosphatidyl inositol-anchored complement regulatory protein found on most cell surfaces. It functions to protect cells from complement attack. The cryo-electro...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.152161599

    authors: He Y,Lin F,Chipman PR,Bator CM,Baker TS,Shoham M,Kuhn RJ,Medof ME,Rossmann MG

    更新日期:2002-08-06 00:00:00

  • Stimulus repetition modulates gamma-band synchronization in primate visual cortex.

    abstract::When a sensory stimulus repeats, neuronal firing rate and functional MRI blood oxygen level-dependent responses typically decline, yet perception and behavioral performance either stay constant or improve. An additional aspect of neuronal activity is neuronal synchronization, which can enhance the impact of neurons on...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1309714111

    authors: Brunet NM,Bosman CA,Vinck M,Roberts M,Oostenveld R,Desimone R,De Weerd P,Fries P

    更新日期:2014-03-04 00:00:00

  • Conformational landscape of cytochrome c folding studied by microsecond-resolved small-angle x-ray scattering.

    abstract::To investigate protein folding dynamics in terms of compactness, we developed a continuous-flow mixing device to make small-angle x-ray scattering measurements with the time resolution of 160 micros and characterized the radius of gyration (R(g)) of two folding intermediates of cytochrome c (cyt c). The early intermed...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.012458999

    authors: Akiyama S,Takahashi S,Kimura T,Ishimori K,Morishima I,Nishikawa Y,Fujisawa T

    更新日期:2002-02-05 00:00:00

  • Molecular modulation of calcium oxalate crystallization by osteopontin and citrate.

    abstract::Calcium oxalate monohydrate (COM), which plays a functional role in plant physiology, is a source of chronic human disease, forming the major inorganic component of kidney stones. Understanding molecular mechanisms of biological control over COM crystallization is central to development of effective stone disease ther...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0307900100

    authors: Qiu SR,Wierzbicki A,Orme CA,Cody AM,Hoyer JR,Nancollas GH,Zepeda S,De Yoreo JJ

    更新日期:2004-02-17 00:00:00

  • A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets.

    abstract::Understanding mammalian spermatozoan development and the events surrounding fertilization has grown slowly, in part because of uncertainty about the number and identity of the cellular components involved. Determination of those transcripts expressed specifically by germ cells should provide an inclusive list of proba...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1635054100

    authors: Schultz N,Hamra FK,Garbers DL

    更新日期:2003-10-14 00:00:00

  • Antibody recognition of a unique tumor-specific glycopeptide antigen.

    abstract::Aberrant glycosylation and the overexpression of certain carbohydrate moieties is a consistent feature of cancers, and tumor-associated oligosaccharides are actively investigated as targets for immunotherapy. One of the most common aberrations in glycosylation patterns is the presentation of a single O-linked N-acetyl...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0915176107

    authors: Brooks CL,Schietinger A,Borisova SN,Kufer P,Okon M,Hirama T,Mackenzie CR,Wang LX,Schreiber H,Evans SV

    更新日期:2010-06-01 00:00:00

  • Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells.

    abstract::This report describes an unbiased method for systematically determining gene function in mammalian cells. A total of 20,704 predicted human full-length cDNAs were tested for induction of the IL-8 promoter. A number of genes, including those for cytokines, receptors, adapters, kinases, and transcription factors, were i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1932773100

    authors: Iourgenko V,Zhang W,Mickanin C,Daly I,Jiang C,Hexham JM,Orth AP,Miraglia L,Meltzer J,Garza D,Chirn GW,McWhinnie E,Cohen D,Skelton J,Terry R,Yu Y,Bodian D,Buxton FP,Zhu J,Song C,Labow MA

    更新日期:2003-10-14 00:00:00

  • Switch from monoallelic to biallelic human IGF2 promoter methylation during aging and carcinogenesis.

    abstract::We have previously linked aging, carcinogenesis, and de novo methylation within the promoter of the estrogen receptor (ER) gene in human colon. We now examine the dynamics of this process for the imprinted gene for insulin-like growth factor II (IGF2). In young individuals, the P2-4 promoters of IGF2 are methylated ex...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.21.11757

    authors: Issa JP,Vertino PM,Boehm CD,Newsham IF,Baylin SB

    更新日期:1996-10-15 00:00:00

  • Modeling nuclear volume isotope effects in crystals.

    abstract::Mass-independent isotope fractionations driven by differences in volumes and shapes of nuclei (the field shift effect) are known in several elements and are likely to be found in more. All-electron relativistic electronic structure calculations can predict this effect but at present are computationally intensive and l...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1216216110

    authors: Schauble EA

    更新日期:2013-10-29 00:00:00

  • Antibiotic-DNA interactions: intermolecular nuclear Overhauser effects in the netropsin-d(C-G-C-G-A-A-T-T-C-G-C-G) complex in solution.

    abstract::The proton markers located in the minor groove of the d(C-G-C-G-A-A-T-T-C-G-C-G) duplex and its netropsin complex have been assigned from measurements of intramolecular nuclear Overhauser effects (NOEs) between exchangeable imino protons and nonexchangeable base protons on the same and adjacent base pairs. Several poi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.21.6424

    authors: Patel DJ

    更新日期:1982-11-01 00:00:00

  • Phosphorylation and subunit organization of axonal neurofilaments determined by scanning transmission electron microscopy.

    abstract::Phosphorylation plays a critical role in controlling the function of cytoskeletal assemblies but no direct method yet exists to measure the phosphorylation state of proteins at the level of individual molecules and assemblies. Herein, we apply scanning transmission electron microscopy in combination with electron ener...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.15.7820

    authors: Leapman RD,Gallant PE,Reese TS,Andrews SB

    更新日期:1997-07-22 00:00:00