Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat

Objective: Although analgesic approaches targeting nerve growth factor (NGF) for the treatment of osteoarthritis (OA) pain remain of clinical interest, neurophysiological mechanisms by which NGF contribute to OA pain remain unclear. We investigated the impact of local elevation of knee joint NGF on...

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Main Authors: Sagar, Devi Rani, Nwosu, Lilian Ngozi, Walsh, David A., Chapman, Victoria
Format: Article
Published: Elsevier 2015
Online Access:https://eprints.nottingham.ac.uk/51922/
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author Sagar, Devi Rani
Nwosu, Lilian Ngozi
Walsh, David A.
Chapman, Victoria
author_facet Sagar, Devi Rani
Nwosu, Lilian Ngozi
Walsh, David A.
Chapman, Victoria
author_sort Sagar, Devi Rani
building Nottingham Research Data Repository
collection Online Access
description Objective: Although analgesic approaches targeting nerve growth factor (NGF) for the treatment of osteoarthritis (OA) pain remain of clinical interest, neurophysiological mechanisms by which NGF contribute to OA pain remain unclear. We investigated the impact of local elevation of knee joint NGF on knee joint, vs remote (hindpaw), evoked responses of spinal neurones in a rodent model of OA pain. Design: In vivo spinal electrophysiology was carried out in anaesthetised rats with established pain behaviour and joint pathology following intra-articular injection of monosodium iodoacetate (MIA), vs injection of saline. Neuronal responses to knee joint extension and flexion, mechanical punctate stimulation of the peripheral receptive fields over the knee and at a remote site (ipsilateral hind paw) were studied before, and following, intra-articular injection of NGF (10 mg/50 ml) or saline. Results: MIA-injected rats exhibited significant local (knee joint) and remote (lowered hindpaw withdrawal thresholds) changes in pain behaviour, and joint pathology. Intra-articular injection of NGF significantly (P<0.05) increased knee extension-evoked firing of spinal neurones and the size of the peripheral receptive fields of spinal neurones (100% increase) over the knee joint in MIA rats, compared to controls. Intra-articular NGF injection did not significantly alter responses of spinal neurones following noxious stimulation of the ipsilateral hind paw in MIA-injected rats. Conclusion: The facilitatory effects of intra-articular injection of NGF on spinal neurones receiving input from the knee joint provide a mechanistic basis for NGF mediated augmentation of OA knee pain, however additional mechanisms may contribute to the spread of pain to remote sites
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spelling nottingham-519222024-08-15T15:17:03Z https://eprints.nottingham.ac.uk/51922/ Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat Sagar, Devi Rani Nwosu, Lilian Ngozi Walsh, David A. Chapman, Victoria Objective: Although analgesic approaches targeting nerve growth factor (NGF) for the treatment of osteoarthritis (OA) pain remain of clinical interest, neurophysiological mechanisms by which NGF contribute to OA pain remain unclear. We investigated the impact of local elevation of knee joint NGF on knee joint, vs remote (hindpaw), evoked responses of spinal neurones in a rodent model of OA pain. Design: In vivo spinal electrophysiology was carried out in anaesthetised rats with established pain behaviour and joint pathology following intra-articular injection of monosodium iodoacetate (MIA), vs injection of saline. Neuronal responses to knee joint extension and flexion, mechanical punctate stimulation of the peripheral receptive fields over the knee and at a remote site (ipsilateral hind paw) were studied before, and following, intra-articular injection of NGF (10 mg/50 ml) or saline. Results: MIA-injected rats exhibited significant local (knee joint) and remote (lowered hindpaw withdrawal thresholds) changes in pain behaviour, and joint pathology. Intra-articular injection of NGF significantly (P<0.05) increased knee extension-evoked firing of spinal neurones and the size of the peripheral receptive fields of spinal neurones (100% increase) over the knee joint in MIA rats, compared to controls. Intra-articular NGF injection did not significantly alter responses of spinal neurones following noxious stimulation of the ipsilateral hind paw in MIA-injected rats. Conclusion: The facilitatory effects of intra-articular injection of NGF on spinal neurones receiving input from the knee joint provide a mechanistic basis for NGF mediated augmentation of OA knee pain, however additional mechanisms may contribute to the spread of pain to remote sites Elsevier 2015-06-30 Article PeerReviewed Sagar, Devi Rani, Nwosu, Lilian Ngozi, Walsh, David A. and Chapman, Victoria (2015) Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat. Osteoarthritis and Cartilage, 23 (6). pp. 906-913. ISSN 1522-9653 https://www.sciencedirect.com/science/article/pii/S1063458415000230 doi:10.1016/j.joca.2015.01.010 doi:10.1016/j.joca.2015.01.010
spellingShingle Sagar, Devi Rani
Nwosu, Lilian Ngozi
Walsh, David A.
Chapman, Victoria
Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat
title Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat
title_full Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat
title_fullStr Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat
title_full_unstemmed Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat
title_short Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat
title_sort dissecting the contribution of knee joint ngf to spinal nociceptive sensitization in a model of oa pain in the rat
url https://eprints.nottingham.ac.uk/51922/
https://eprints.nottingham.ac.uk/51922/
https://eprints.nottingham.ac.uk/51922/