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Prospective Administration of Anti-NGF Treatment Effectively Suppresses Functional Connectivity Alterations Following Cancer-Induced Bone Pain in Mice


Buehlmann, David; Ielacqua, Giovanna Diletta; Xandry, Jael; Rudin, Markus (2019). Prospective Administration of Anti-NGF Treatment Effectively Suppresses Functional Connectivity Alterations Following Cancer-Induced Bone Pain in Mice. Pain, 160(1):151-159.

Abstract

Cancer-induced bone pain is abundant among advanced stage cancer patients and arises from a primary tumor in the bone or skeletal metastasis of common cancer types such as breast, lung or prostate cancer. Recently, antibodies targeting nerve growth factor (NGF) have been shown to effectively relieve neuropathic and inflammatory pain states in mice and in humans. While efficacy has been shown in mice on a behavioral level, effectiveness in preventing pain-induced functional rearrangements in the central nervous system has not been shown. Therefore we assessed longitudinal whole-brain functional connectivity using resting-state fMRI in a mouse model of cancer-induced bone pain. We found functional connectivity between major hubs of ascending and descending pain pathways such as the periaqueductal gray, amygdala, thalamus as well as cortical somatosensory regions to be affected by a developing cancer pain state. These changes could be successfully prevented through prospective administration of a monoclonal anti-NGF antibody (mAb911). This indicates efficacy of anti-NGF treatment to prevent pain-induced adaptations in brain functional networks following persistent nociceptive input from cancer-induced bone pain. Additionally, it highlights the suitability of resting-state fMRI readouts as an indicator of treatment response on the basis of longitudinal functional network changes.

Abstract

Cancer-induced bone pain is abundant among advanced stage cancer patients and arises from a primary tumor in the bone or skeletal metastasis of common cancer types such as breast, lung or prostate cancer. Recently, antibodies targeting nerve growth factor (NGF) have been shown to effectively relieve neuropathic and inflammatory pain states in mice and in humans. While efficacy has been shown in mice on a behavioral level, effectiveness in preventing pain-induced functional rearrangements in the central nervous system has not been shown. Therefore we assessed longitudinal whole-brain functional connectivity using resting-state fMRI in a mouse model of cancer-induced bone pain. We found functional connectivity between major hubs of ascending and descending pain pathways such as the periaqueductal gray, amygdala, thalamus as well as cortical somatosensory regions to be affected by a developing cancer pain state. These changes could be successfully prevented through prospective administration of a monoclonal anti-NGF antibody (mAb911). This indicates efficacy of anti-NGF treatment to prevent pain-induced adaptations in brain functional networks following persistent nociceptive input from cancer-induced bone pain. Additionally, it highlights the suitability of resting-state fMRI readouts as an indicator of treatment response on the basis of longitudinal functional network changes.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology

04 Faculty of Medicine > Institute of Biomedical Engineering
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Neurology
Health Sciences > Neurology (clinical)
Health Sciences > Anesthesiology and Pain Medicine
Uncontrolled Keywords:Anesthesiology and Pain Medicine, Neurology, Clinical Neurology
Language:English
Date:1 January 2019
Deposited On:18 Sep 2018 14:18
Last Modified:29 Jul 2020 07:45
Publisher:Lippincott Williams & Wilkins
ISSN:0304-3959
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1097/j.pain.0000000000001388
PubMed ID:30161041

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