NGF deprivation-induced gene expression: after ten years, where do we stand?

Freeman, Robert S.; Burch, R; Crowder, Robert J.; Lomb, David J.; Schoell, Matthew C; Straub, Jennifer A; Xie, Liang

doi:10.1016/s0079-6123(03)46008-1

Cited by 83 publications

(63 citation statements)

References 116 publications

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“…First, NGF is a known mediator of sensory and nociceptive nerve function and substance P is a sensory pain-associated neuropeptide released at synapses; thus, both contribute to hyperalgesia (increased sensitivity to pain) [2,18,45]. Second, NGF and substance P can contribute to nerve ingrowth [1,6,13,44], and without NGF, all sensory neurons will undergo apoptosis [7]. Both factors work in synergy and may be directly involved in mediating innervation and pain in the lower back [35,39].…”

Section: Discussionmentioning

confidence: 99%

Periprosthetic UHMWPE Wear Debris Induces Inflammation, Vascularization, and Innervation After Total Disc Replacement in the Lumbar Spine

Veruva

Lanman

Isaza

et al. 2017

Clinical Orthopaedics &Amp; Related Research

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Background The pathophysiology and mechanisms driving the generation of unintended pain after total disc replacement (TDR) remain unexplored. Ultrahigh-molecular-weight polyethylene (UHMWPE) wear debris from TDRs is known to induce inflammation, which may result in pain.Questions/purposes The purpose of this study was to determine whether (1) periprosthetic UHMWPE wear debris induces immune responses that lead to the production of tumor necrosis factor-a (TNFa) and interleukin (IL)-1ß, the vascularization factors, vascular endothelial growth factor (VEGF) and platelet-derived growth factorbb (PDGFbb), and the innervation/pain factors, nerve growth factor (NGF) and substance P; (2) the number of Clinical Orthopaedics and Related Research ®A Publication of The Association of Bone and Joint Surgeons® macrophages is associated with the production of the aforementioned factors; (3) the wear debris-induced inflammatory pathogenesis involves an increase in vascularization and associated innervation. Methods Periprosthetic tissues from our collection of 11 patients with contemporary TDRs were evaluated using polarized light microscopy to quantify UHMWPE wear particles. The major reason for revision (mean implantation time of 3 years [range, 1-6 years]) was pain. For control subjects, biopsy samples from four patients with degenerative disc disease with severe pain and autopsy samples from three normal patients with no history of back pain were also investigated. Immunohistochemistry and histology were used to identify secretory factors, macrophages, and blood vessels. Immunostained serial sections were imaged at 9200 magnification and using MATLAB and NIH ImageJ, a threshold was determined for each factor and used to quantify positive staining normalized to tissue sectional area. The Mann-Whitney U test was used to compare results from different patient groups, whereas the Spearman Rho test was used to determine correlations. Significance was based on p \ 0.05. Results The mean percent area of all six inflammatory, vascularization, and innervation factors was higher in TDR tissues when compared with normal disc tissues. Based on nonparametric data analysis, those factors showing the most significant increase included TNFa (5.17 ± 1.76 versus 0.05 ± 0.03, p = 0.02), VEGF (3.02 ± 1.01 versus 0.02 ± 0.002, p = 0.02), and substance P (4.15 ± 1.01 versus 0.08 ± 0.04, p = 0.02). The mean percent area for IL-1ß (2.41 ± 0.66 versus 0.13 ± 0.13, p = 0.01), VEGF (3.02 ± 1.01 versus 0.34 ± 0.29, p = 0.04), and substance P (4.15 ± 1.01 versus 1.05 ± 0.46, p = 0.01) was also higher in TDR tissues when compared with disc tissues from patients with painful degenerative disc disease. Five of the factors, TNFa, IL-1ß, VEGF, NGF, and substance P, strongly correlated with the number of wear particles, macrophages, and blood vessels. The most notable correlations included TNFa with wear particles (p \ 0.001, q = 0.63), VEGF with macrophages (p = 0.001, q = 0.71), and NGF with blood vessels (p\0.001, q = 0.70). Of particular signif...

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Section: Discussionmentioning

confidence: 99%

Periprosthetic UHMWPE Wear Debris Induces Inflammation, Vascularization, and Innervation After Total Disc Replacement in the Lumbar Spine

Veruva

Lanman

Isaza

et al. 2017

Clinical Orthopaedics &Amp; Related Research

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“…Numerous growth factors have been identified that influence the survival and plasticity of neurons, including the neurotrophins (NGF, 2 brain-derived neurotrophic factor, NT-3, and NT-4), basic fibroblast growth factor, insulin-like growth factor 1 (IGF-1), and epidermal growth factor (EGF). These different factors activate receptors with intrinsic tyrosine kinase activity, which then engage downstream kinase cascades, resulting in the activation of transcription factors.…”

mentioning

confidence: 99%

Growth Factor Signals in Neural Cells

Martin

Brenneman

Golden

et al. 2009

Journal of Biological Chemistry

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Individual neurons express receptors for several different growth factors that influence the survival, growth, neurotransmitter phenotype, and other properties of the cell. Although there has been considerable progress in elucidating the molecular signal transduction pathways and physiological responses of neurons and other cells to individual growth factors, little is known about if and how signals from different growth factors are integrated within a neuron. In this study, we determined the interactive effects of nerve growth factor, insulin-like growth factor 1, and epidermal growth factor on the activation status of downstream kinase cascades and transcription factors, cell survival, and neurotransmitter production in neural cells that express receptors for all three growth factors. We document considerable differences in the quality and quantity of intracellular signaling and eventual phenotypic responses that are dependent on whether cells are exposed to a single or multiple growth factors. Dual stimulations that generated the greatest antagonistic or synergistic actions, compared with a theoretically neutral summation of their two activities, yielded the largest eventual change of neuronal phenotype indicated by the ability of the cell to produce norepinephrine or resist oxidative stress. Combined activation of insulin-like growth factor 1 and epidermal growth factor receptors was particularly notable for antagonistic interactions at some levels of signal transduction and norepinephrine production, but potentiation at other levels of signaling and cytoprotection. Our findings suggest that in true physiological settings where multiple growth factors are present, activation of one receptor type may result in molecular and phenotypic responses that are different from that observed in typical experimental paradigms in which cells are exposed to only a single growth factor at a time.Numerous growth factors have been identified that influence the survival and plasticity of neurons, including the neurotrophins (NGF, 2 brain-derived neurotrophic factor, NT-3, and NT-4), basic fibroblast growth factor, insulin-like growth factor 1 (IGF-1), and epidermal growth factor (EGF). These different factors activate receptors with intrinsic tyrosine kinase activity, which then engage downstream kinase cascades, resulting in the activation of transcription factors. For example, NGF activates the TrkA receptor that engages the Raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway resulting in activation of transcription factors, including AP1 (1-3); IGF-1 activates the IGF-1 receptor that is coupled to phosphatidylinositol trisphosphate kinase, Akt kinase, and forkhead transcription factors of the FOXO family (4, 5); and EGF receptors engage the Raf-MEK-ERK pathway (6, 7). Many neural cells express receptors for multiple growth factors, each of which induce similar effects on the survival, differentiation, and function of the cells. Although there has been considerable progress ...

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“…Nerve growth factor (NGF), normally synthesized in neuronal target tissues and retrogradely transported to the neuronal cell body to exert its trophic functions, is essential for the survival and maintenance of sympathetic and sensory nerves 21,22 . It can stimulate the growth of axon, maintain the diameter of axon, prevent the death of adult neurons after injury, regulate the plasticity of synaptic and the transmission of neurotransmitter.…”

Section: Exogenous Nrg1 Can Inhibit Diabetic Neuropathic Painmentioning

confidence: 99%

Exogenous neuregulin-1 attenuates STZ-induced diabetic peripheral neuropathic pain in rats

Zhou¹,

Xia²,

Liu³

et al. 2017

Acta Cir. Bras.

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Purpose: To investigate whether modulating NRG1 could attenuate diabetic neuropathic pain and analyze the underlying mechanism. Methods: Male SD rats were randomly divided into control group, diabetic group, NRG1 intervention group. After STZ-induced 2 weeks, NRG1 intervention daily for consecutive 7 days. 4 weeks after NRG1 intervention, both the mechanical withdrawal threshold and the morphological changes of the dorsal root ganglion and sural nerve were observed. Meanwhile, the expression of NGF, IL-1β, TNF-α in spinal cord were determined. Results: Compared with the diabetic group, NRG1 treatment improved the mechanical withdrawal threshold in diabetic rats, pathological changes of dorsal root ganglion and sural nerve were alleviated by NRG1 treatment with electron microscopy imagine. Moreover, compared with the control group, the expression of NGF was significantly decreased and the production of IL-1β, TNF-α were markedly induced in diabetic group. Furthermore, NRG1 treatment could normalized the above effect as compared to diabetic group. Conclusion: NRG1 exerted positive effects on the behavioral and pathological changes of rats with STZ-induced diabetic neuropathic pain, the underlying mechanism might be related to the promotion of NGF excretion and the inhibition of inflammatory cytokines excretion.

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NGF deprivation-induced gene expression: after ten years, where do we stand?

Cited by 83 publications

References 116 publications

Periprosthetic UHMWPE Wear Debris Induces Inflammation, Vascularization, and Innervation After Total Disc Replacement in the Lumbar Spine

Periprosthetic UHMWPE Wear Debris Induces Inflammation, Vascularization, and Innervation After Total Disc Replacement in the Lumbar Spine

Growth Factor Signals in Neural Cells

Exogenous neuregulin-1 attenuates STZ-induced diabetic peripheral neuropathic pain in rats

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