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Long-term pain relief in canine osteoarthritis by a single intra-articular injection of resiniferatoxin, a potent TRPV1 agonist.

ABSTRACT: The translational potential of analgesic approaches emerging from basic research can be augmented by client-owned dog trials. 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 degeneration (Charcot joint) in any of the dogs. To amplify the effective use of canine subjects in translational analgesia research, we report a high-quality canine dorsal root ganglion transcriptome. Some targets for analgesia are highly conserved both in protein sequence and level of expression within a target tissue while others diverge substantially from the human. This knowledge is especially important for development of analgesics aimed at peripheral molecular targets and provides a template for informed translational research. The peripheral site of action, long duration of analgesia, apparent safety, and retention of coordination, all resulting from a single dose suggest that intra-articular RTX may be an effective intervention for osteoarthritis pain with few or no side effects and lead to an improved quality of life.

SUBMITTER: Iadarola MJ

PROVIDER: S-EPMC8121156 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:INTRODUCTION:Intra-articular (IA) injection of hyaluronic acid (HA) and corticosteroid (CS) is a common treatment for osteoarthritis (OA) of the knee. As a drug treatment for patients with depression, duloxetine has been shown in many studies to effectively relieve the pain of OA and improve function of the knee joint. However, evidence regarding the efficacy of IA injection of HA+CS combined with duloxetine for pain management in patients with OA of the knee is lacking. The aim of this study was to test the hypothesis that IA injection of HA+CS combined with duloxetine could achieve pain management superior to that of IA injection of HA+CS alone in patients experiencing knee OA pain. METHODS:This study will adopt a prospective, randomised, open-label blind endpoint study design. In total, 150 patients with OA of the knee will be enrolled in the study. The participants will be randomly allocated to receive either a single IA injection of HA+CS combined with duloxetine or a single IA injection of HA+CS alone, and both groups will complete a 24-week follow-up to assess pain and functional improvements. The primary outcome measure is the change in the weekly mean of the 24?hours average pain scores from baseline to the end of 24 weeks in patients with OA of the knee, and the secondary outcomes include the response to treatment, changes from baseline in the brief pain inventory, improvement in the Western Ontario and McMaster Universities Osteoarthritis index scores, patient global impression of improvement scale, Hospital Anxiety and Depression Scale and adverse events during the 24-week follow-up. The data will be analysed by the intention-to-treat principle. ETHICS APPROVAL AND DISSEMINATION:This study was approved by the institutional ethics committee of the Beijing Tiantan Hospital (approval number: KY 2019-086-02). The results of the study will be published in peer-reviewed journals, and the findings will be presented at scientific meetings. TRIAL REGISTRATION NUMBER:ClinicalTrials.gov Identifier: NCT04117893; Pre-results.

Project description:BackgroundRecently, in an open pilot study, we found up to two years, a potential pain-relieving effect of intra-articular gold micro-particles using the patient's synovial fluid for patients with knee osteoarthritis (KOA). During the study the excluded group of patients, due to multisite pain, co-morbidities, and other exclusion criteria., received intra-articular gold micro-particles using hyaluronic acid,. We aimed to identify if pre-treatment characteristics influence the global outcome two years after intra-articular treatment for painful KOA with gold microparticles using hyaluronic acid.MethodsUsing hyaluronic acid as the carrier, 136 patients with KOA received intraarticular injections with 20 mg gold microparticles (72.000 particles, 20-40 μm in diameter). In the analysis, we included the Global Rating of Change Scale, Pain Detect Questionnaire (PDQ), Body Mass Index (BMI), and Kellgren & Lawrence score at the inclusion, Western Ontario, and McMaster Universities Osteoarthritis Index (WOMAC) sub-scores for pain, stiffness, and function at inclusion and two years.ResultsOn the Global Rating Change Scale, 69.1% of patients reported a positive effect, 28.7% no effect, and 2.2% worse. PDQ and the three WOMAC subscores all improved at two years of follow-up. PDQ ≥ 13 (P = 0.028), BMI (P = 0.022) and Kellgren & Lawrence grade 4 (P = 0.028) at inclusion reduced the effect with a minor odds ratio compared to the baseline effect of treatment (P = 0.025). WOMAC subscores at inclusion did not influence the outcome (P > 0.5).ConclusionsSevere osteoarthritis, obesity, and neuropathic pain, reduced the effect of intra-articular gold microparticles for knee OA.Trial registrationThe study followed the principles of the Declaration of Helsinki and was approved by the local ethics committee of the North Denmark Region by 27/07/2016 (N-20,160,045). The regional data protection agency approved the project by 06/07/2016 (2008-58-0028, ID 2016 - 116) and registered in ClinicalTrial.Gov by 04/01/2018 (NCT03389906).

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Long-term pain relief in canine osteoarthritis by a single intra-articular injection of resiniferatoxin, a potent TRPV1 agonist.

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