Sensitization of transient receptor potential vanilloid 4 and increasing its endogenous ligand 5,6-epoxyeicosatrienoic acid in rats with monoiodoacetate-induced osteoarthritis

In conclusion, TRPV4 was sensitized in the knee joints of MIA rats through phosphorylation in dorsal root ganglion neurons, along with an increase in the levels of its endogenous ligand 5,6-EET. The analgesic effects of the TRPV4 antagonist in the OA pain model rats suggest that TRPV4 may be a potent target for OA pain relief.
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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In conclusion, with study of the frailty syndrome still in its infancy, frailty analysis remains a major challenge. It is a challenge that needs to be overcome in order to shed light on the multiple mechanisms involved in the pathogenesis of this syndrome. Although several mechanisms contribute to frailty, immune system alteration seems to play a central role: this syndrome is characterized by increased levels of pro-inflammatory markers and the resulting pro-inflammatory status can have negative effects on various organs. Future studies should aim to better clarify the immune system alteration in frailty, and seek to esta...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Nerve growth factor (NGF), a neurotrophin involved in the development of the nervous system, plays a key role in pain by sensitizing peripheral nociceptors following tissue injury or inflammation. This peripheral sensitization by NGF is mediated through binding to the high-affinity receptor tropomyosin-related kinase (Trk)A localized to peptidergic sensory nerves.1 The NGF-TrkA complex is internalized and transported to the dorsal root ganglion, where it increases TRPV1 phosphorylation and the expression and release of neuropeptides including substance P and calcitonin gene-related peptide.
Source: Osteoarthritis and Cartilage - Category: Rheumatology Authors: Tags: Editorial Source Type: research
CONCLUSIONS: The expression of KCNA2 is decreased in the DRG neurons of rats with OA pain likely as a result of enhanced methylation of Kcna2 promoter region. PMID: 31140423 [PubMed - in process]
Source: Journal of Southern Medical University - Category: Universities & Medical Training Authors: Tags: Nan Fang Yi Ke Da Xue Xue Bao Source Type: research
Conclusion: The present study suggests that the extract of LMZ attenuates CFA-induced inflammatory pain by suppressing the ERK1/2 and NF-κB signaling pathway at both peripheral and central level. Introduction Pain is one of the most common symptoms in clinical practice, and inflammatory pain is the most important type of pain (Patapoutian et al., 2009). Inflammatory pain is a growing global health problem. In generally, there is a common course of progression in inflammation and pain share. When patients experience inflammation, they may develop hyperalgesia or allodynia to various mechanical, thermal, or che...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, we found that senescent chondrocytes isolated from OA patients secrete more EVs compared with nonsenescent chondrocytes. These EVs inhibit cartilage ECM deposition by healthy chondrocytes and can induce a senescent state in nearby cells. We profiled the miR and protein content of EVs isolated from the synovial fluid of OA joints from mice with SnCs. After treatment with a molecule to remove SnCs, termed a senolytic, the composition of EV-associated miR and protein was markedly altered. The senolytic reduced OA development and enhanced chondrogenesis, and these were attributable to several specific differenti...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Joint pain is the defining symptom of osteoarthritis (OA) but its origin and mechanisms remain unclear. Here, we investigated an unprecedented role of osteoclast-initiated subchondral bone remodeling in sensory innervation for OA pain. We show that osteoclasts secrete netrin-1 to induce sensory nerve axonal growth in subchondral bone. Reduction of osteoclast formation by knockout of receptor activator of nuclear factor kappa-B ligand (Rankl) in osteocytes inhibited the growth of sensory nerves into subchondral bone, dorsal root ganglion neuron hyperexcitability, and behavioral measures of pain hypersensitivity in OA mice. ...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
We report on a peripheral interventional approach that uses intra-articular injection of the ultrapotent TRPV1 agonist resiniferatoxin (RTX) to produce a selective long-term chemoinactivation of nociceptive primary afferent nerve endings for pain control in naturally occurring canine osteoarthritis. A single injection of 10 µg of RTX, produced suppression of pain, improvement in gait, weight bearing, and improvement in the dog's activities of daily living lasting 4 months or longer. Two to 3 years after the injection, there are no alterations to suggest that removal of inflammatory pain caused accelerated joint degen...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
CONCLUSIONS: The acute onset of numbness with or without intolerable pain in the ring and little fingers after a long-term remission period following initial surgery for CuTS in patients with elbow osteoarthritis appears to be the characteristic clinical profile of recurrent CuTS caused by ganglion. As ganglia are often not palpable, ultrasonography and magnetic resonance imaging are recommended for accurate diagnosis. PMID: 29734908 [PubMed - in process]
Source: Hand Surgery - Category: Surgery Authors: Tags: J Hand Surg Asian Pac Vol Source Type: research
Study Design. Controlled, interventional animal study. Objective. To examine the effect of an inhibitor of acid-sensing ion channel 3 (ASIC3) on pain-related behavior induced by application of the nucleus pulposus (NP) onto the dorsal root ganglion (DRG) in rats. Summary of Background Data. ASIC3 is associated with acidosis pain in inflamed or ischemic tissues and is expressed in sensory neurons and NP cells. The ASIC3 inhibitor, APETx2, increases the mechanical threshold of pain in models of knee osteoarthritis or postoperative pain. However, the efficacy of APETx2 for pain relief in the NP application model remains unk...
Source: Spine - Category: Orthopaedics Tags: Basic Science Source Type: research
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Source: Journal of Orthopaedic Research - Category: Orthopaedics Authors: Tags: Research Article Source Type: research
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