scholarly journals Serotonin Receptor 2A/C Is Involved in Electroacupuncture Inhibition of Pain in an Osteoarthritis Rat Model

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Aihui Li ◽  
Yu Zhang ◽  
Lixing Lao ◽  
Jiajia Xin ◽  
Ke Ren ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Rat Model ◽  
Serotonin Receptor ◽  
Weight Bearing ◽  
Pain Modulation ◽  
Double Labeling ◽  
Osteoarthritis Pain ◽  
Raphe Magnus ◽  
Monosodium Iodoacetate ◽  
Underlying Mechanisms

Osteoarthritis currently has no cure. Acupuncture can benefit patients with knee osteoarthritis by providing pain relief, improving joint function and serving as an effective complement to standard care. However, the underlying mechanisms of its effects are still not completely understood. The present study, an investigation of the effectiveness and mechanisms of electroacupuncture (EA) in attenuating osteoarthritis pain in a rat model, is focused on the involvement of 5-hydroxytryptamine 2A/C (5-HT2A/C) receptors, which play an important role in pain modulation at the spinal level. Osteoarthritis was induced under isoflurane anesthesia by a single intraarticular injection of monosodium iodoacetate (3 mg/50 μL/rat) into one hind leg of each rat. EA was given at acupoints GB 30 and ST 36 on days 1–4 after the injection. Vehicle or ketanserin, a 5-HT2A/C receptor antagonist, was given intraperitoneally (1 mg kg−1) or intrathecally (5 μg or 10 μg/10 μL), 30 min before each EA treatment. Assessment of weight-bearing difference between injected and uninjected hind legs was done on days 0, 1–4 and 7. Fos /serotonin and serotonin/Fluorogold double labeling were performed to determine EA activation of serotonergic neurons in the nucleus raphe magnus (NRM) that project to spinal cord. The results showed that EA significantly decreases weight-bearing difference compared to sham EA. Ketanserin pretreatment blocked the analgesic effect of EA but did not influence weight bearing in sham EA control rats. EA also activated serotonergic NRM neurons that project to the spinal cord. These data show that EA inhibits osteoarthritis-induced pain by enhancing spinal 5-HT2A/2C receptor activity.

Targeted Treatment of Experimental Spinal Cord Glioma With Dual Gene-Engineered Human Neural Stem Cells

Neurosurgery ◽  
2015 ◽  
Vol 79 (3) ◽  
pp. 481-491 ◽  
Author(s):  
Alexander E. Ropper ◽  
Xiang Zeng ◽  
Hariprakash Haragopal ◽  
Jamie E. Anderson ◽  
Zaid Aljuboori ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Growth Rate ◽  
Neural Stem Cells ◽  
Tumor Growth ◽  
Rat Model ◽  
Weight Bearing ◽  
Tumor Growth Rate ◽  
Intramedullary Spinal Cord ◽  
Human Neural Stem Cells

Abstract BACKGROUND There are currently no satisfactory treatments or experimental models showing autonomic dysfunction for intramedullary spinal cord gliomas (ISCG). OBJECTIVE To develop a rat model of ISCG and investigate whether genetically engineered human neural stem cells (F3.hNSCs) could be developed into effective therapies for ISCG. METHODS Immunodeficient/Rowett Nude rats received C6 implantation of G55 human glioblastoma cells (10K/each). F3.hNSCs engineered to express either cytosine deaminase gene only (i.e., F3.CD) or dual genes of CD and thymidine kinase (i.e., F3.CD-TK) converted benign 5-fluorocytosine and ganciclovir into oncolytic 5-fluorouracil and ganciclovir-triphosphate, respectively. ISCG rats received injection of F3.CD-TK, F3.CD, or F3.CD-TK debris near the tumor epicenter 7 days after G55 seeding, followed with 5-FC (500 mg/kg/5 mL) and ganciclovir administrations (25 mg/kg/1 mL/day × 5/each repeat, intraperitoneal injection). Per humane standards for animals, loss of weight-bearing stepping in the hindlimb was used to determine post-tumor survival. Also evaluated were autonomic functions and tumor growth rate in vivo. RESULTS ISCG rats with F3.CD-TK treatment survived significantly longer (37.5 ± 4.78 days) than those receiving F3.CD (21.5 ± 1.75 days) or F3.CD-TK debris (19.3 ± 0.85 days; n = 4/group; P <.05, median rank test), with significantly improved autonomic function and reduced tumor growth rate. F3.DC-TK cells migrated diffusively into ISCG clusters to mediate oncolytic effect. CONCLUSION Dual gene-engineered human neural stem cell regimen markedly prolonged survival in a rat model that emulates somatomotor and autonomic dysfunctions of human cervical ISCG. F3.CD-TK may provide a novel approach to treating clinical ISCG.

scholarly journals Effects of Dipsacus asperoides and Phlomis umbrosa Extracts in a Rat Model of Osteoarthritis

Plants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2030
Author(s):  
Jin Mi Chun ◽  
A Yeong Lee ◽  
Byeong Cheol Moon ◽  
Goya Choi ◽  
Joong-Sun Kim
Keyword(s):  
Knee Joint ◽  
Rat Model ◽  
Weight Bearing ◽  
Similar Efficacy ◽  
Herbal Products ◽  
Korean Medicine ◽  
Histopathological Features ◽  
Serum Cytokines ◽  
Monosodium Iodoacetate ◽  
Model Weight

The implementation of the Nagoya Protocol highlighted the importance of identifying alternative herbal products that are as effective as traditional medicine. Dipsacus asperoides and Phlomis umbrosa, two species used in the Korean medicine ‘Sok-dan’, are used for the treatment of bone- and arthritis-related diseases, and they are often mixed or misused. To identify herbal resources with similar efficacy, we compared the effects of D. asperoides extract (DAE) and P. umbrosa extract (PUE) on osteoarthritis (OA) in a monosodium iodoacetate (MIA)-induced OA rat model. Weight-bearing distribution, serum cytokines, histopathological features, and the expression of matrix metalloproteinases (MMPs) of knee joint tissues were examined in the OA rats treated with DAE and PUE (200 mg/kg) for 21 days. DAE and PUE restored weight-bearing distribution, inhibited the production of serum cytokines, and alleviated the histopathological features of the OA knee tissue. DAE or PUE treatment decreased OA-induced overexpression of MMP-2, MMP-9, and MMP-13 in the knee joint tissue. This study demonstrated the efficacy of both DAE and PUE in an MIA-induced OA model, providing a basis for the clinical use of these products in traditional Korean medicine.

A scientific research study on the management of Manyasthamba (Cervical Spondylosis) with Nasya and Nasapana

2019 ◽  
Vol 4 (04) ◽  
Author(s):  
Unnikrishnan V S ◽  
Prashanth A S ◽  
Madhusudan Kulkarni
Keyword(s):  
Spinal Cord ◽  
Clinical Data ◽  
Food Habits ◽  
Cervical Spondylosis ◽  
Research Study ◽  
Weight Bearing ◽  
Scientific Research ◽  
Modern Era ◽  
Treatment Aspect

The science of life Ayurveda, not only deals with the prevention of diseases by maintaining health but also with the alleviation of diseases. In this ultra modern era due to change in lifestyles, sedentary works and food habits, people are unable to follow the Dinacharya and Ritucharya as explained in the classics, which may lead to different diseases. Due to improper postural habits, weight bearing and other unwholesome diets and habits there are higher the chances of discomfort and disease pertaining to spinal cord. Manyasthambha is one such condition that disturbs a big population due to today’s alterations in lifestyle. Here an effort is made to study and understand the role of Nasya Karma, Nasaapana and Shamanaushadhi like Vyoshadi Guggulu in the treatment aspect of this disease. Nasya Karma and Nasaapana provided highly significant results in all the symptoms of Manyasthambha. As per the clinical data, ‘Nasaapana is found to be more effective than Nasya Karma’. So it can be concluded that better results can be obtained with Shaddharana Yoga as Amapachana, Nasaapana with Mashabaladi Kwatha followed by Vyoshadi Guggulu as Shamanoushadhi.

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

scholarly journals Analgesic and Anti-Inflammatory Effects of Aucklandia lappa Root Extracts on Acetic Acid-Induced Writhing in Mice and Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Plants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 42
Author(s):  
Hee-Geun Jo ◽  
Geon-Yeong Lee ◽  
Chae Yun Baek ◽  
Ho Sueb Song ◽  
Donghun Lee
Keyword(s):  
Acetic Acid ◽  
Weight Bearing ◽  
Bone Diseases ◽  
Joint Disease ◽  
Root Extracts ◽  
Raw264.7 Macrophages ◽  
Age Related ◽  
Monosodium Iodoacetate ◽  
Anti Inflammatory

Osteoarthritis (OA) is an age-related joint disease and one of the most common degenerative bone diseases among elderly people. The currently used therapeutic strategies relying on nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids for OA are often associated with gastrointestinal, cardiovascular, and kidney disorders, despite being proven effective. Aucklandia lappa is a well-known traditional medicine. The root of A. lappa root has several bioactive compounds and has been in use as a natural remedy for bone diseases and other health conditions. We evaluated the A. lappa root extracts on OA progression as a natural therapeutic agent. A. lappa substantially reduced writhing numbers in mice induced with acetic acid. Monosodium iodoacetate (MIA) was injected into the rats through their knee joints of rats to induce experimental OA, which shows similar pathological characteristics to OA in human. A. lappa substantially reduced the MIA-induced weight-bearing of hind limb and reversed the cartilage erosion in MIA rats. IL-1β, a representative inflammatory mediator in OA, was also markedly decreased by A. lappa in the serum of MIA rats. In vitro, A. lappa lowered the secretion of NO and suppressed the IL-1β, COX-2, IL-6, and iNOS production in RAW264.7 macrophages activated with LPS. Based on its analgesic and anti-inflammatory effects, A. lappa could be a potential remedial agent against OA.

scholarly journals Multi-pronged neuromodulation intervention engages the residual motor circuitry to facilitate walking in a rat model of spinal cord injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marco Bonizzato ◽  
Nicholas D. James ◽  
Galyna Pidpruzhnykova ◽  
Natalia Pavlova ◽  
Polina Shkorbatova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Stress Responses ◽  
Learning Algorithm ◽  
Lumbar Spinal Cord ◽  
Cord Injury ◽  
Potential Synergy ◽  
Lumbar Spinal ◽  
Deep Brain

AbstractA spinal cord injury usually spares some components of the locomotor circuitry. Deep brain stimulation (DBS) of the midbrain locomotor region and epidural electrical stimulation of the lumbar spinal cord (EES) are being used to tap into this spared circuitry to enable locomotion in humans with spinal cord injury. While appealing, the potential synergy between DBS and EES remains unknown. Here, we report the synergistic facilitation of locomotion when DBS is combined with EES in a rat model of severe contusion spinal cord injury leading to leg paralysis. However, this synergy requires high amplitudes of DBS, which triggers forced locomotion associated with stress responses. To suppress these undesired responses, we link DBS to the intention to walk, decoded from cortical activity using a robust, rapidly calibrated unsupervised learning algorithm. This contingency amplifies the supraspinal descending command while empowering the rats into volitional walking. However, the resulting improvements may not outweigh the complex technological framework necessary to establish viable therapeutic conditions.

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