Nerve growth factor concentrations in the synovial fluid from healthy dogs and dogs with secondary osteoarthritis

Isola, Maurizio; Ferrari, Vincenzo; Miolo, Alda; Stabile, Fabio; Bernardini, D; Carnier, Paolo; Busetto, Roberto

doi:10.3415/vcot-10-04-0051

Cited by 37 publications

(25 citation statements)

References 43 publications

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“…For example, NGF immunoreactivity was shown in dorsal spinal ganglia in experimental radiculopathy 18 . A similar overexpression of neuropeptides including NGF is found in animal models with experimentally induced arthritis 19–21 and OA in dogs 22 . These robust NGF-related reactions following pain and inflammation suggest that anti-NGF regimens may result in a reduction of pain perception.…”

Section: Animal Studies – Pain and Effect Of Anti-ngf Regimenssupporting

confidence: 67%

Nerve growth factor: an update on the science and therapy

Seidel

Wise

Lane

2013

Osteoarthritis and Cartilage

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SUMMARY Objective Nerve growth factor (NGF) is a key regulator of nociceptive pain and thus appears to be an interesting target molecule for an innovative class of analgesic medication. We set out to review the principles of neurogenic inflammation and results of anti-NGF regimens in animal studies as well as clinical trials with patients with back pain and osteoarthritis (OA). Design We searched using Google Scholar Search and Pubmed as well as through conference reports for articles and abstracts related to NGF and clinical trials using anti-NGF regimens. We report on efficacy findings and adverse events (AEs) related to these agents in this review. Results We identified five full articles and eight abstract reports relating to anti-NGF agents studied for use in back pain and in OA. Conclusions Anti-NGF agents either alone or in combination with non-steroidal anti-inflammatory agents (NSAIDs) were more efficacious for the treatment of pain in a number of trials of knee and hip pain compared to NSAIDs alone. However, adverse effects that included rapidly progressive OA and joint replacement were more common in patients treated with anti-NGF and NSAIDs than either treatment alone. Anti-NGF treatment related neurologic symptoms including paresthesias, and potentially other types of adverse effects were usually transient but warrant additional investigation.

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Section: Animal Studies – Pain and Effect Of Anti-ngf Regimenssupporting

confidence: 67%

Nerve growth factor: an update on the science and therapy

Seidel

Wise

Lane

2013

Osteoarthritis and Cartilage

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“…While local injection of NGF has consistently shown to produce mechanical hyperalgesia in humans 17, 55, 60 and animals 26, 39, 44 , the expression of NGF in the peritoneal fluid of patients with endometriosis seems not to be proportional to pain levels 8 . Such a lack of correlation between pain and local NGF levels has been observed in humans 46 and animals 27 suffering from osteoarthritis, a condition where the pain is sensitive to monoclonal antibodies directed against NGF 14 . This might indicate that NGF acts synergistically with other pro-algesic mediators, its local levels not necessarily being representative of its full involvement in endometriosis pain.…”

Section: Discussionmentioning

confidence: 99%

Screening the Role of Pronociceptive Molecules in a Rodent Model of Endometriosis Pain

Álvarez

Levine

2014

The Journal of Pain

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Chronic pain is a major symptom in patients with endometriosis, a common gynecologic condition affecting women in their reproductive years. While many pro-algesic substances are produced by endometriosis lesions, experimental evidence supporting their relative roles is still lacking. Furthermore, it is unclear whether these pro-algesic agents directly activate nociceptors to induce endometriosis pain. To determine their relative contribution to pain associated with endometriosis we evaluated the intrathecal administration of oligodeoxynucleotides antisense to mRNA for receptors for three pro-nociceptive mediators known to be produced by ectopic endometrium. Two weeks after the implant of autologous uterine tissue onto the gastrocnemius muscle, local mechanical hyperalgesia was observed in operated rats. Intrathecal antisense oligodeoxynucleotides (AS ODN) targeting mRNA for the interleukin 6 receptor-signaling complex subunit glycoprotein 130 and the NGF tyrosine kinase receptor A (TrkA), but not their mismatch ODNs, reversibly attenuated mechanical hyperalgesia at the implant site. In contrast, intrathecal AS ODN targeting the tumor necrosis factor receptor 1 (TNFR1), at a dose that markedly inhibited intramuscularly injected TNFα had only a small antihyperalgesic effect in this model. These results indicate the relative contribution of pronociceptive mediators produced by ectopic endometrial tissue to endometriosis pain. The experimental approach presented here provides a novel method to evaluate for the differential contribution of mediators produced by other painful lesions as well as endometriosis solutions lesions as targets for novel treatment of pain syndromes. Perspective This article presents evidence for the relative contribution of pro-algesic mediators to primary hyperalgesia displayed by rats submitted to a model of endometriosis pain. This approach can be used to identify potential targets for the treatment of endometriosis pain.

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“…In mouse models of OA, intra-articular injections of NGF produced prolonged weight-bearing asymmetry. NGF is also upregulated in the synovial fluid of dogs with OA secondary to other conditions [11]. Pecchi et al showed that in a culture of human OA chondrocytes, mechanical stress and exposure to interleukin (IL)-1β increased expression of NGF [12].…”

Section: Pain Mechanisms In Oamentioning

confidence: 99%

A Mechanism-Based Approach to the Management of Osteoarthritis Pain

Cohen

Lee

2015

Curr Osteoporos Rep

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Pain from osteoarthritis (OA) affects millions of people worldwide, yet treatments are limited to acetaminophen, NSAIDs, physical therapy, and ultimately, surgery when there is significant disability. In recent years, our understanding of pain pathways in OA has developed considerably. Though joint damage and inflammation play a significant role in pain generation, it is now understood that both central and peripheral nervous system mechanisms exacerbate symptoms. Evolving management strategies for OA address central factors (e.g., sleep difficulties, catastrophizing, and depression) with treatments such as cognitive behavioral therapy and exercise. In addition, emerging data suggest that antibodies against peripheral signaling neuropeptides, such as nerve growth factor-1 (NGF-1), may significantly alleviate pain. However, concerns regarding potential adverse effects, such as rapidly progressive OA, still remain. A nuanced understanding is essential if we are to make headway in developing more effective treatments for OA.

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Nerve growth factor concentrations in the synovial fluid from healthy dogs and dogs with secondary osteoarthritis

Cited by 37 publications

References 43 publications

Nerve growth factor: an update on the science and therapy

Nerve growth factor: an update on the science and therapy

Screening the Role of Pronociceptive Molecules in a Rodent Model of Endometriosis Pain

A Mechanism-Based Approach to the Management of Osteoarthritis Pain

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