scholarly journals Age‐related molecular changes in the lumbar dorsal root ganglia of mice: Signs of sensitization, and inflammatory response

JOR Spine ◽  
2020 ◽  
Vol 3 (4) ◽  
Author(s):  
Kathleen Vincent ◽  
Chethana Prabodhanie Gallage Dona ◽  
Todd J Albert ◽  
Chitra Lekha Dahia
Keyword(s):  
Inflammatory Response ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Molecular Changes ◽  
Age Related

MP8-06 PREVENTIVE EFFECTS OF CALORIC RESTRICTION ON AGING-ASSOCIATED BIOLOGICAL AND MOLECULAR CHANGES IN THE RAT BLADDER AND DORSAL ROOT GANGLIA

2015 ◽  
Vol 193 (4S) ◽  
Author(s):  
Hiroki Ito ◽  
Naoki Aizawa ◽  
Rino Sugiyama ◽  
Jun Kamei ◽  
Yoshiyuki Akiyama ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Molecular Changes ◽  
Rat Bladder ◽  
Preventive Effects

scholarly journals Inhibiting BDNF/TrkB.T1 receptor improves resiniferatoxin-induced postherpetic neuralgia through decreasing ASIC3 signaling in dorsal root ganglia

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiang Wei ◽  
Lina Wang ◽  
Jie Hua ◽  
Xiao-hong Jin ◽  
Fuhai Ji ◽  
...  
Keyword(s):  
Nervous System ◽  
Inflammatory Response ◽  
Protein Expression ◽  
Dorsal Root Ganglia ◽  
Postherpetic Neuralgia ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Neuronal Excitability ◽  
Thermal Hyperalgesia ◽  
Pc 12 Cells

Abstract Background Postherpetic neuralgia (PHN) is a devastating complication after varicella-zoster virus infection. Brain-derived neurotrophic factor (BDNF) has been shown to participate in the pathogenesis of PHN. A truncated isoform of the tropomyosin receptor kinase B (TrkB) receptor TrkB.T1, as a high-affinity receptor of BDNF, is upregulated in multiple nervous system injuries, and such upregulation is associated with pain. Acid-sensitive ion channel 3 (ASIC3) is involved in chronic neuropathic pain, but its relation with BDNF/TrkB.T1 in the peripheral nervous system (PNS) during PHN is unclear. This study aimed to investigate whether BDNF/TrkB.T1 contributes to PHN through regulating ASIC3 signaling in dorsal root ganglia (DRGs). Methods Resiniferatoxin (RTX) was used to induce rat PHN models. Mechanical allodynia was assessed by measuring the paw withdrawal thresholds (PWTs). Thermal hyperalgesia was determined by detecting the paw withdrawal latencies (PWLs). We evaluated the effects of TrkB.T1-ASIC3 signaling inhibition on the behavior, neuronal excitability, and inflammatory response during RTX-induced PHN. ASIC3 short hairpin RNA (shRNA) transfection was used to investigate the effect of exogenous BDNF on inflammatory response in cultured PC-12 cells. Results RTX injection induced mechanical allodynia and upregulated the protein expression of BDNF, TrkB.T1, ASIC3, TRAF6, nNOS, and c-Fos, as well as increased neuronal excitability in DRGs. Inhibition of ASIC3 reversed the abovementioned effects of RTX, except for BDNF and TrkB.T1 protein expression. In addition, inhibition of TrkB.T1 blocked RTX-induced mechanical allodynia, activation of ASIC3 signaling, and hyperexcitability of neurons. RTX-induced BDNF upregulation was found in both neurons and satellite glia cells in DRGs. Furthermore, exogenous BDNF activated ASIC3 signaling, increased NO level, and enhanced IL-6, IL-1β, and TNF-α levels in PC-12 cells, which was blocked by shRNA-ASIC3 transfection. Conclusion These findings demonstrate that inhibiting BDNF/TrkB.T1 reduced inflammation, decreased neuronal hyperexcitability, and improved mechanical allodynia through regulating the ASIC3 signaling pathway in DRGs, which may provide a novel therapeutic target for patients with PHN.

scholarly journals Sensitization of primary cultures from rat dorsal root ganglia with lipopolysaccharide (LPS) requires a robust inflammatory response

2021 ◽  
Author(s):  
Franz Nürnberger ◽  
Stephan Leisengang ◽  
Daniela Ott ◽  
Jolanta Murgott ◽  
Rüdiger Gerstberger ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Primary Cultures ◽  
Somatosensory System ◽  
Low Doses ◽  
Tnf Α ◽  
Wide Range ◽  
Ratio Imaging ◽  
Pre Treatment

Abstract Objective We investigated whether it is possible to induce a state of “LPS-sensitization” in neurons of primary cultures from rat dorsal root ganglia by pre-treatment with ultra-low doses of LPS. Methods DRG primary cultures were pre-treated with low to ultra-low doses of LPS (0.001–0.1 µg/ml) for 18 h, followed by a short-term stimulation with a higher LPS-dose (10 µg/ml for 2 h). TNF-α in the supernatants was measured as a sensitive read out. Using the fura-2 340/380 nm ratio imaging technique, we further investigated the capsaicin-evoked Ca2+-signals in neurons from DRG, which were pre-treated with a wide range of LPS-doses. Results Release of TNF-α evoked by stimulation with 10 µg/ml LPS into the supernatant was not significantly modified by pre-exposure to low to ultra-low LPS-doses. Capsaicin-evoked Ca2+-signals were significantly enhanced by pre-treatment with LPS doses being above a certain threshold. Conclusion Ultra-low doses of LPS, which per se do not evoke a detectable inflammatory response, are not sufficient to sensitize neurons (Ca2+-responses) and glial elements (TNF-α-responses) of the primary afferent somatosensory system.

Inhibiting BDNF/TrkB receptor improves resiniferatoxin-induced postherpetic neuralgia through decreasing ASIC3 signaling in dorsal root ganglia

2020 ◽  
Author(s):  
Xiang Wei ◽  
Lina Wang ◽  
Jie Hua ◽  
Xiao-hong Jin ◽  
Fuhai Ji ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Protein Expression ◽  
Dorsal Root Ganglia ◽  
Postherpetic Neuralgia ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Neuronal Excitability ◽  
Thermal Hyperalgesia ◽  
Varicella Zoster Virus Infection ◽  
Pc 12 Cells

Abstract Background Postherpetic neuralgia (PHN) is a devastating complication after varicella-zoster virus infection. Brain-derived neurotrophic factor (BDNF) has been shown to participate in the pathogenesis of PHN. Tropomyosin receptor kinase B (TrkB), an endogenous high-affinity receptor of BDNF is abundantly expressed in primary sensory neurons. Acid-sensitive ion channel 3 (ASIC3) is involved in chronic neuropathic pain, but its relation with BDNF/TrkB during PHN is unclear. This study aimed to investigate whether BDNF/TrkB contributes to PHN through regulating ASIC3 signaling in dorsal root ganglia (DRGs). Methods Resiniferatoxin (RTX) was used to induce rat PHN models. Mechanical allodynia was assessed by measuring the paw withdrawal thresholds (PWTs). Thermal hyperalgesia was determined by measuring the paw withdrawal latencies (PWLs). We evaluated the effects of TrkB/ASIC3 signaling inhibition on the behavioral test, neuronal excitability and inflammatory response in rat models of PHN. ASIC3 short hairpin RNA (shRNA) transfection was used to investigate the effect of exogenous BDNF on inflammatory response in cultured PC-12 cells. Results RTX resulted in significant mechanical allodynia, upregulated the protein expression of BDNF, TrkB, ASIC3, TRAF6, nNOS and c-Fos, and increased neuronal excitability in DRGs. Inhibition of ASIC3 reversed the above-mentioned effects of RTX, except for BDNF and TrkB protein expression. In addition, inhibition of TrkB blocked RTX-induced mechanical allodynia, activation of ASIC3 signaling and hyperexcitability of neurons. RTX-induced activation of BDNF was found in both neurons and satellite glia cells in DRGs. Furthermore, exogenous BDNF activated ASIC3 signaling, increased NO level and enhanced IL-6, IL-1β, TNF-α level in PC-12 cells, which was blocked by shRNA-ASIC3 transfection. Conclusion These findings demonstrate that inhibiting BDNF/TrkB reduced inflammation, decreased neuronal hyperexcitability and improved mechanical allodynia through regulating ASIC3 signaling pathway in DRGs, which may provide a novel therapeutic target for patients with PHN.

895 Ageing-associated biological and molecular changes in the rat bladder and dorsal root ganglia – preventive effect of caloric restriction

2015 ◽  
Vol 14 (2) ◽  
pp. e895-e895a
Author(s):  
H. Ito ◽  
N. Aizawa ◽  
R. Sugiyama ◽  
J. Kamei ◽  
Y. Akiyama ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Preventive Effect ◽  
Molecular Changes ◽  
Rat Bladder

Membrane-associated microtubular areays induced in proximal myelinated processes of dorsal root ganglia by large doses of vitamin B6

1986 ◽  
Vol 44 ◽  
pp. 368-369
Author(s):  
V.J. Montpetit ◽  
S. Dancea ◽  
L. Tryphonas ◽  
D.F. Clapin
Keyword(s):  
Animal Model ◽  
Endoplasmic Reticulum ◽  
Dorsal Root Ganglia ◽  
Rough Endoplasmic Reticulum ◽  
Dorsal Root ◽  
Vitamin B6 ◽  
Morphological Changes ◽  
Model System ◽  
Sensory Nerves ◽  
Peripheral Sensory

Very large doses of pyridoxine (vitamin B6) are neurotoxic in humans, selectively affecting the peripheral sensory nerves. We have undertaken a study of the morphological and biochemical aspects of pyridoxine neurotoxicity in an animal model system. Early morphological changes in dorsal root ganglia (DRG) associated with pyridoxine megadoses include proliferation of neurofilaments, ribosomes, rough endoplasmic reticulum, and Golgi complexes. We present in this report evidence of the formation of unique aggregates of microtubules and membranes in the proximal processes of DRG which are induced by high levels of pyridoxine.

scholarly journals OP0083 DORSAL ROOT GANGLIA INFILTRATING MACROPHAGES MAINTAIN OSTEOARTHRITIS PAIN

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 55.2-56
Author(s):  
R. Raoof ◽  
C. Martin ◽  
H. De Visser ◽  
J. Prado ◽  
S. Versteeg ◽  
...  
Keyword(s):  
Knee Joint ◽  
Dorsal Root Ganglia ◽  
Immune Cells ◽  
Dorsal Root ◽  
Weight Bearing ◽  
Joint Damage ◽  
Osteoarthritis Pain ◽  
Knee Pathology ◽  
Femoral Condyles ◽  
Over Time

Background:Pain is a major debilitating symptom of knee osteoarthritis (OA). However, the extent of joint damage in OA does not correlate well with the severity of pain. The mechanisms that govern OA pain are poorly understood. Immune cells infiltrating nervous tissue may contribute to pain maintenance.Objectives:Here we investigated the role of macrophages in the initiation and maintenance of OA pain.Methods:Knee joint damage was induced by an unilateral injection of mono-iodoacetate (MIA) or after application of a groove at the femoral condyles of rats fed on high fat diet. Pain-like behaviors were followed over time using von Frey test and dynamic weight bearing. Joint damage was assessed by histology. Dorsal root ganglia (DRG) infiltrating immune cells were assessed over time using flow cytometry. To deplete monocytes and macrophages, Lysmcrex Csfr1-Stop-DTR were injected intrathecal or systemically with diptheria toxin (DT).Results:Intraarticular monoiodoacetate injection induced OA and signs of persistent pain, such as mechanical hyperalgesia and deficits in weight bearing. The persisting pain-like behaviors were associated with accumulation of F4/80+macrophages with an M1-like phenotype in the lumbar DRG appearing from 1 week after MIA injection, and that persisted till at least 4 weeks after MIA injection. Macrophages infiltrated DRG were also observed in the rat groove model of OA, 12 weeks after application of a groove at the femoral condyles. Systemic or local depletion of DRG macrophages during established MIA-induced OA completely ablated signs of pain, without affecting MIA-induced knee pathology. Intriguingly when monocytes/macrophages were depleted prior to induction of osteoarthritis, pain-like behaviors still developed, however these pain-like behaviors did not persist over time.In vitro,sensory neurons innervating the affected OA joint programmed macrophages into a M1 phenotype. Local repolarization of M1-like DRG macrophages towards M2 by intrathecal injection of M2 macrophages or anti-inflammatory cytokines resolved persistent OA-induced pain.Conclusion:Overall we show that macrophages infiltrate the DRG after knee damage and acquire a M1-like phenotype and maintain pain independent of the lesions in the knee joint. DRG-infiltrating macrophages are not required for induction of OA pain. Reprogramming M1-like DRG-infiltrating macrophages may represent a potential strategy to treat OA pain.Acknowledgments:This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreements No 814244 and No 642720. Dutch Arthritis SocietyDisclosure of Interests:Ramin Raoof: None declared, Christian Martin: None declared, Huub de Visser: None declared, Judith Prado: None declared, Sabine Versteeg: None declared, Anne Heinemans: None declared, Simon Mastbergen: None declared, Floris Lafeber Shareholder of: Co-founder and shareholder of ArthroSave BV, Niels Eijkelkamp: None declared

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