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. 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

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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

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Rheumatology, Orthopaedics and Dermatology
Identification Number: https://doi.org/10.1016/j.joca.2015.01.010
Depositing User: Healy, Jane
Date Deposited: 21 May 2018 14:15
Last Modified: 08 May 2020 09:15
URI: https://eprints.nottingham.ac.uk/id/eprint/51922

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