scholarly journals Corrigendum to “Relationship between Pain Behavior and Changes in KCNA2 Expression in the Dorsal Root Ganglia of Rats with Osteoarthritis”

2021 ◽  
Vol 2021 ◽  
pp. 1-2
Author(s):  
Qihong Zhao ◽  
Lei Fan ◽  
Jiafeng Wang ◽  
Xiaoming Deng

2021 ◽  
Vol 14 ◽  
Author(s):  
Mengke Wang ◽  
Xia Cai ◽  
Yueying Wang ◽  
Shizhen Li ◽  
Na Wang ◽  
...  

Neurologic damage often leads to neuropathic pain, for which there are no effective treatments owing to its complex pathogenesis. The purinergic receptor P2X4 is closely associated with neuropathic pain. Astragalin (AST), a compound that is used in traditional Chinese medicine, has protective effects against allergic dermatitis and neuronal injury, but its mechanism of action is not well understood. The present study investigated whether AST can alleviate neuropathic pain in a rat model established by chronic constriction injury (CCI) to the sciatic nerve. The model rats exhibited pain behavior and showed increased expression of P2X4 and the activated satellite glial cell (SGC) marker glial fibrillary acidic protein in dorsal root ganglia (DRG). AST treatment partly abrogated the upregulation of P2X4, inhibited SGC activation, and alleviated pain behavior in CCI rats; it also suppressed ATP-activated currents in HEK293 cells overexpressing P2X4. These data demonstrate that AST relieves neuropathic pain by inhibiting P2X4 and SGC activation in DRG, highlighting its therapeutic potential for clinical pain management.


2016 ◽  
Vol 4;19 (4;5) ◽  
pp. E589-E600
Author(s):  
Salahadin Abdi

Background: Chemotherapy-induced neuropathic pain is difficult to treat. Pentoxifylline inhibits the production of inflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Objective: The aims of our study were to investigate the analgesic and preventive effects of pentoxifylline on paclitaxel-induced neuropathic pain in rats and to identify its mechanisms of action. Study Design: Controlled animal study. Methods: Neuropathic pain was induced with intraperitoneally injected paclitaxel on 4 alternate days in male Sprague-Dawley rats. Pentoxifylline was administered systemically as a single injection and a continuous infusion before or after the injection of paclitaxel. The mechanical threshold for allodynia was measured by using von Frey filaments. Protein levels and localization of inflammatory cytokines were performed by using Western blotting and immunohistochemistry, respectively. Results: After the rats developed neuropathic pain behavior, a single intraperitoneal injection and continuous infusion of pentoxifylline ameliorated paclitaxel-induced mechanical allodynia. In addition, systemic infusion of pentoxifylline in the early phase of the development of pain behavior delayed the onset of paclitaxel-induced pain behavior. Paclitaxel increased the levels of the catalytic subunit α of protein kinase A, phosphorylated nuclear factor κB, TNF-α, and IL-1β in the lumbar dorsal root ganglia. Pentoxifylline decreased the paclitaxel-induced TNF-α and IL1β levels. In addition, IL-1β was expressed in neurons and satellite cells in the lumbar dorsal root ganglia after paclitaxel. Limitations: Although this study was performed in the animal model by well-designed manner, clinical study will be needed to confirm the analgesic effect of pentoxifylline. Conclusion: Pentoxifylline alleviated chemotherapy-induced neuropathic pain in rats by reducing the levels of inflammatory cytokines in dorsal root ganglia and may be effective chemotherapyinduced neuropathic pain in patients. Key words: Chemotherapy, chronic pain, inflammatory cytokines, neuropathic pain, paclitaxel, pain behavior, pain treatment, pentoxifylline, phosphodiesterase inhibitor


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Qihong Zhao ◽  
Lei Fan ◽  
Jiafeng Wang ◽  
Xiaoming Deng

Objective. To investigate the relationship between pain behavior and potassium voltage-gated channel subfamily A member 2 (KCNA2) expression in dorsal root ganglia (DRGs) of rats with osteoarthritis (OA). Methods. Male Sprague-Dawley rats were randomly divided into three groups: blank control group (group C), normal saline group (group S), and group OA. Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured one day before injection and one, two, four, and six weeks after injection. At one, two, four, and six weeks after injection, pathological knee joint changes and activated transcription factor-3 (ATF-3) and KCNA2 expressions in DRGs were analyzed. Results. Compared with preinjection, PWMT and PWTL at two, four, and six weeks after injection were significantly decreased in the group OA (P<0.05 or 0.01). Compared with group C, PWMT and PWTL at two, four, and six weeks after injection were significantly decreased in the group OA (P<0.05 or 0.01). In the group OA, slight local articular cartilage surface destruction was found at week one. The cartilage surface destruction gradually developed, and the exacerbation of cartilage matrix reduction and bone hyperplasia were increasingly aggravated and eventually evolved into advanced OA in the second to sixth weeks. Compared with group C, ATF-3 expression was significantly increased, and KCNA2 expression was significantly decreased in the group OA at two, four, and six weeks after injection (P<0.05 or 0.01). Compared to baseline, ATF-3 expression was significantly increased, and KCNA2 expression was significantly decreased in the group OA (P<0.05 or 0.01). Conclusion. Pain behavior in OA rats was associated with decreased KCNA2 expression in DRGs.


2011 ◽  
Vol 469 (9) ◽  
pp. 2568-2576 ◽  
Author(s):  
Katsumasa Tanimoto ◽  
Tsuneo Takebayashi ◽  
Takeshi Kobayashi ◽  
Noritsugu Tohse ◽  
Toshihiko Yamashita

Author(s):  
V.J. Montpetit ◽  
S. Dancea ◽  
L. Tryphonas ◽  
D.F. Clapin

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.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 55.2-56
Author(s):  
R. Raoof ◽  
C. Martin ◽  
H. De Visser ◽  
J. Prado ◽  
S. Versteeg ◽  
...  

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


Author(s):  
Irene Riquelme ◽  
Miguel Angel Reina ◽  
André P. Boezaart ◽  
Francisco Reina ◽  
Virginia García-García ◽  
...  

2021 ◽  
Vol 22 (11) ◽  
pp. 5499
Author(s):  
Veronica Corsetti ◽  
Carla Perrone-Capano ◽  
Michael Sebastian Salazar Intriago ◽  
Elisabetta Botticelli ◽  
Giancarlo Poiana ◽  
...  

Dorsal root ganglia (DRG) neurons synthesize acetylcholine (ACh), in addition to their peptidergic nature. They also release ACh and are cholinoceptive, as they express cholinergic receptors. During gangliogenesis, ACh plays an important role in neuronal differentiation, modulating neuritic outgrowth and neurospecific gene expression. Starting from these data, we studied the expression of choline acetyltransferase (ChAT) and vesicular ACh transporter (VAChT) expression in rat DRG neurons. ChAT and VAChT genes are arranged in a “cholinergic locus”, and several splice variants have been described. Using selective primers, we characterized splice variants of these cholinergic markers, demonstrating that rat DRGs express R1, R2, M, and N variants for ChAT and V1, V2, R1, and R2 splice variants for VAChT. Moreover, by RT-PCR analysis, we observed a progressive decrease in ChAT and VAChT transcripts from the late embryonic developmental stage (E18) to postnatal P2 and P15 and in the adult DRG. Interestingly, Western blot analyses and activity assays demonstrated that ChAT levels significantly increased during DRG ontogenesis. The modulated expression of different ChAT and VAChT splice variants during development suggests a possible differential regulation of cholinergic marker expression in sensory neurons and confirms multiple roles for ACh in DRG neurons, both in the embryo stage and postnatally.


2008 ◽  
Vol 295 (5) ◽  
pp. L858-L865 ◽  
Author(s):  
Kevin Kwong ◽  
Marian Kollarik ◽  
Christina Nassenstein ◽  
Fei Ru ◽  
Bradley J. Undem

The lungs and esophagus are innervated by sensory neurons with somata in the nodose, jugular, and dorsal root ganglion. These sensory ganglia are derived from embryonic placode (nodose) and neural crest tissues (jugular and dorsal root ganglia; DRG). We addressed the hypothesis that the neuron's embryonic origin (e.g., placode vs. neural crest) plays a greater role in determining particular aspects of its phenotype than the environment in which it innervates (e.g., lungs vs. esophagus). This hypothesis was tested using a combination of extracellular and patch-clamp electrophysiology and single-cell RT-PCR from guinea pig neurons. Nodose, but not jugular C-fibers innervating the lungs and esophagus, responded to α,β-methylene ATP with action potential discharge that was sensitive to the P2X3 (P2X2/3) selective receptor antagonist A-317491. The somata of lung- and esophagus-specific sensory fibers were identified using retrograde tracing with a fluorescent dye. Esophageal- and lung-traced neurons from placodal tissue (nodose neurons) responded similarly to α,β-methylene ATP (30 μM) with a large sustained inward current, whereas in neurons derived from neural crest tissue (jugular and DRG neurons), the same dose of α,β-methylene ATP resulted in only a transient rapidly inactivating current or no detectable current. It has been shown previously that only activation of P2X2/3 heteromeric receptors produce sustained currents, whereas homomeric P2X3 receptor activation produces a rapidly inactivating current. Consistent with this, single-cell RT-PCR analysis revealed that the nodose ganglion neurons innervating the lungs and esophagus expressed mRNA for P2X2 and P2X3 subunits, whereas the vast majority of jugular and dorsal root ganglia innervating these tissues expressed only P2X3 mRNA with little to no P2X2 mRNA expression. We conclude that the responsiveness of C-fibers innervating the lungs and esophagus to ATP and other purinergic agonists is determined more by their embryonic origin than by the environment of the tissue they ultimately innervate.


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