Faculty Opinions recommendation of Active immunisation targeting nerve growth factor attenuates chronic pain behaviour in murine osteoarthritis.

2020 ◽  
Author(s):  
Susanne Grässel
Keyword(s):  
Chronic Pain ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Active Immunisation ◽  
Pain Behaviour ◽  
Nerve Growth

scholarly journals Active immunisation targeting nerve growth factor attenuates chronic pain behaviour in murine osteoarthritis

2019 ◽  
Vol 78 (5) ◽  
pp. 672-675 ◽  
Author(s):  
Isabell S von Loga ◽  
Aadil El-Turabi ◽  
Luke Jostins ◽  
Jadwiga Miotla-Zarebska ◽  
Jennifer Mackay-Alderson ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neurite Outgrowth ◽  
Meta Analysis ◽  
Spontaneous Pain ◽  
Vaccine Strategy ◽  
Active Immunisation ◽  
Pain Behaviour ◽  
Nerve Growth

ObjectivesNerve growth factor (NGF) has emerged as a key driver of pain in osteoarthritis (OA) and antibodies to NGF are potent analgesics in human disease. Here, we validate a novel vaccine strategy to generate anti-NGF antibodies for reversal of pain behaviour in a surgical model of OA.MethodsVirus-like particles were derived from the cucumber mosaic virus (CuMV) and coupled to expressed recombinant NGF to create the vaccine. 10-week-old male mice underwent partial meniscectomy to induce OA or sham-surgery. Spontaneous pain behaviour was measured by Linton incapacitance and OA severity was quantified using OARSI histological scoring. Mice (experimental and a sentinel cohort) were inoculated with CuMVttNGF (Vax) or CuMVttctrl (Mock) either before surgery or once pain was established. Efficacy of anti-NGF from the plasma of sentinel vaccinated mice was measured in vitro using a neurite outgrowth assay in PC12 cells.ResultsAnti-NGF titres were readily detectable in the vaccinated but not mock vaccinated mice. Regular boosting with fresh vaccine was required to maintain anti-NGF titres as measured in the sentinel cohort. Both prophylactic and therapeutic vaccination demonstrated a reversal of pain behaviour by incapacitance testing, and a meta-analysis of the two studies showing analgesia at peak anti-NGF titres was highly statistically significant. Serum anti-NGF was able to inhibit neurite outgrowth equivalent to around 150 ug/mL of recombinant monoclonal antibody.ConclusionsThis study demonstrates therapeutic efficacy of a novel NGF vaccine strategy that reversibly alleviates spontaneous pain behaviour in surgically induced murine OA.

A possible role for nerve growth factor in the augmentation of sodium channels in models of chronic pain

2000 ◽  
Vol 854 (1-2) ◽  
pp. 19-29 ◽  
Author(s):  
Harry J. Gould ◽  
Trevor N. Gould ◽  
John D. England ◽  
Dennis Paul ◽  
Z.P. Liu ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Sodium Channels ◽  
Nerve Growth

scholarly journals Antagonism of Nerve Growth Factor-TrkA Signaling and the Relief of Pain

2011 ◽  
Vol 115 (1) ◽  
pp. 189-204 ◽  
Author(s):  
Patrick W. Mantyh ◽  
Martin Koltzenburg ◽  
Lorne M. Mendell ◽  
Leslie Tive ◽  
David L. Shelton ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pain Relief ◽  
Adverse Events ◽  
Tissue Injury ◽  
Sympathetic Neurons ◽  
Nerve Growth ◽  
Cognate Receptor ◽  
Kinase A

Nerve growth factor (NGF) was originally discovered as a neurotrophic factor essential for the survival of sensory and sympathetic neurons during development. However, in the adult NGF has been found to play an important role in nociceptor sensitization after tissue injury. The authors outline mechanisms by which NGF activation of its cognate receptor, tropomyosin-related kinase A receptor, regulates a host of ion channels, receptors, and signaling molecules to enhance acute and chronic pain. The authors also document that peripherally restricted antagonism of NGF-tropomyosin-related kinase A receptor signaling is effective for controlling human pain while appearing to maintain normal nociceptor function. Understanding whether there are any unexpected adverse events and how humans may change their behavior and use of the injured/degenerating tissue after significant pain relief without sedation will be required to fully appreciate the patient populations that may benefit from these therapies targeting NGF.

scholarly journals Temporal mismatch between pain behaviour, skin Nerve Growth Factor and intra-epidermal nerve fibre density in trigeminal neuropathic pain

2014 ◽  
Vol 15 (1) ◽  
pp. 1 ◽  
Author(s):  
Laura J Evans ◽  
Alison R Loescher ◽  
Fiona M Boissonade ◽  
Simon A Whawell ◽  
Peter P Robinson ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Nerve Fibre ◽  
Pain Behaviour ◽  
Nerve Growth ◽  
Fibre Density ◽  
Trigeminal Neuropathic Pain

scholarly journals A Virus-Like Particle-Based Anti-Nerve Growth Factor Vaccine Reduces Inflammatory Hyperalgesia: Potential Long-Term Therapy for Chronic Pain

2010 ◽  
Vol 186 (3) ◽  
pp. 1769-1780 ◽  
Author(s):  
Till A. Röhn ◽  
William T. Ralvenius ◽  
Jolly Paul ◽  
Petra Borter ◽  
Marcela Hernandez ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Term Therapy ◽  
Inflammatory Hyperalgesia ◽  
Nerve Growth ◽  
Virus Like Particle ◽  
Long Term Therapy

scholarly journals Anti-nerve growth factor monoclonal antibodies for the control of pain in dogs and cats

2018 ◽  
Vol 184 (1) ◽  
pp. 23-23 ◽  
Author(s):  
Masataka Enomoto ◽  
Patrick W Mantyh ◽  
Joanna Murrell ◽  
John F Innes ◽  
B Duncan X Lascelles
Keyword(s):  
Chronic Pain ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Sympathetic Neurons ◽  
Critical Role ◽  
Current Status ◽  
Effective Control ◽  
Novel Therapy ◽  
Nerve Growth ◽  
Species Specific

Nerve growth factor (NGF) is essential for the survival of sensory and sympathetic neurons during development. However, in the adult, NGF and its interaction with tropomyosin receptor kinase A receptor (TrkA) has been found to play a critical role in nociception and nervous system plasticity in pain conditions. Thus, various monoclonal antibody (mAb) therapies targeting this pathway have been investigated in the development of new pharmacotherapies for chronic pain. Although none of the mAbs against NGF are yet approved for use in humans, they look very promising for the effective control of pain. Recently, species-specific anti-NGF mAbs for the management of osteoarthritis (OA)-associated pain in dogs and cats has been developed, and early clinical trials have been conducted. Anti-NGF therapy looks to be both very effective and very promising as a novel therapy against chronic pain in dogs and cats. This review outlines the mechanism of action of NGF, the role of NGF in osteoarthritis, research in rodent OA models and the current status of the development of anti-NGF mAbs in humans. Furthermore, we describe and discuss the recent development of species-specific anti-NGF mAbs for the treatment of OA-associated pain in veterinary medicine.

scholarly journals Efficacy and Safety of an Anti-nerve Growth Factor Antibody (Frunevetmab) for the Treatment of Degenerative Joint Disease-Associated Chronic Pain in Cats: A Multisite Pilot Field Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Margaret E. Gruen ◽  
Jamie A. E. Myers ◽  
B. Duncan X. Lascelles
Keyword(s):  
Chronic Pain ◽  
Nerve Growth Factor ◽  
Pain Management ◽  
Growth Factor ◽  
Unmet Need ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Efficacy And Safety ◽  
Nerve Growth ◽  
Objectively Measured

Background: Pain management for cats with degenerative joint disease (DJD) remains a critical unmet need. Recent work has shown promise for a feline-specific anti-nerve growth factor monoclonal antibody (frunevetmab) to deliver safe and effective pain management. Our objectives were to evaluate the efficacy and safety of frunevetmab administered twice using two administration routes (subcutaneous and intravenous) compared to placebo.Methods: This was a randomized placebo-controlled, double-masked study. After a week-long pain and activity baseline, 126 cats were randomized to receive injections of frunevetmab (IV then SC; n = 42 or SC then SC; n = 43) or placebo (IV then SC; n = 41) on Days 0 and 28. Owners completed questionnaires on Days 14, 28, 42, and 56. Accelerometry data were collected continuously throughout.Results: Owner questionnaire results showed significant improvement in frunevetmab-treated cats [compared to placebo; (p < 0.05)] at Days 42 and 56; no difference was found between routes of administration for frunevetmab. All groups had decreased objectively measured weekly activity from baseline; frunevetmab-treated cats had a mean decrease of 0.9%, while placebo-treated cats had a mean decrease of 9.3%. Treatments were generally well-tolerated. The majority of adverse events included dermatitis/alopecia related to activity-monitor collars; these occurred in a higher percentage of frunevetmab, compared to placebo, treated cats.Conclusions and Clinical Relevance: Treatment with frunevetmab provided improvements in owner ratings of mobility over treatment with placebo; these results were supported by objectively measured accelerometry. Frunevetmab has the potential to address a critical gap in the treatment of chronic pain in cats.

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