title: Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat.
abstract: 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.
  
  
  METHODS
  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 μg/50 μl) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK; School of Life Sciences, University of Nottingham, Nottingham, NG7 2UH, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Sagar
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK; Department of Academic Rheumatology, University of Nottingham, Clinical Sciences Building, Nottingham City Hospital, NG5 1PB, UK.
authors.forename: L
authors.initials: L
authors.lastname: Nwosu
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK; Department of Academic Rheumatology, University of Nottingham, Clinical Sciences Building, Nottingham City Hospital, NG5 1PB, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Walsh
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK; School of Life Sciences, University of Nottingham, Nottingham, NG7 2UH, UK. Electronic address: victoria.chapman@nottingham.ac.uk.
authors.forename: V
authors.initials: V
authors.lastname: Chapman
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D007270:Injections, Intra-Articular; D019807:Iodoacetic Acid; D008297:Male; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D059225:Nociception / Q000187:drug effects / Q000502:physiology; D010003:Osteoarthritis / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D010146:Pain / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation / Q000379:methods; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D020932:Nerve Growth Factor; D019807:Iodoacetic Acid
keywords: Monosodium iodoacetate; Osteoarthritis; Pain; Spinal