title: Injury of primary afferent neurons may contribute to osteoarthritis induced pain: an experimental study using the collagenase model in rats.
abstract: OBJECTIVE
  Pain exacerbated by movement and loading on the joint is the major symptom of osteoarthritis (OA), but the mechanisms of chronic pain in this pathology are still poorly understood. Using the intra-articular (i.a.) injection of collagenase in the knee of rats as a model of OA, we aimed at evaluating whether injury of sensory neurons may contribute to the development of OA-associated nociception.
  
  
  METHODS
  OA was induced by i.a. injection of collagenase into the left knee joint of adult male Wistar rats. Histopathological changes and movement and loading-induced nociception were assessed for 6 weeks. A time-course analysis of the expression of the neuronal injury markers activating transcription factor-3 (ATF-3) and neuropeptide Y (NPY) and of the neuropeptide SP in the dorsal root ganglion (DRG) was performed. Gabapentin's effect on nociception was evaluated, as well as the expression of the α2δ-1 voltage-gated calcium channel subunit.
  
  
  RESULTS
  Collagenase induced the development of OA-like histopathological changes and of movement-induced nociception. Altered expression of ATF-3, NPY and SP was observed in the DRG, correlating with the degree of articular degeneration after 6 weeks of disease progression. Repeated administration of gabapentin reversed the nociceptive responses 6 weeks after the induction of OA. α2δ-1 was upregulated in the DRG.
  
  
  CONCLUSIONS
  By inducing nociceptive behaviours associated with relevant joint structural changes, the i.a. injection of collagenase presents itself as a pertinent model for the study of OA pain. The findings in this study support the hypothesis that injury of sensory neurons innervating OA joints may be a significant element in the mechanisms of OA-associated pain.
authors.affiliation: Departamento de Biologia Experimental, Centro de Investigação Médica da Faculdade de Medicina da Universidade do Porto (CIM-FMUP), Alameda Prof Hernâni Monteiro, 4200-319 Porto, Portugal; Morphysiology of the Somatosensory System Group, Instituto de Biologia Molecular e Celular (IBMC), Rua do Campo Alegre 823, 4150-180 Porto, Portugal. Electronic address: sadaes@med.up.pt.
authors.forename: S
authors.initials: S
authors.lastname: Adães
authors.affiliation: Departamento de Biologia Experimental, Centro de Investigação Médica da Faculdade de Medicina da Universidade do Porto (CIM-FMUP), Alameda Prof Hernâni Monteiro, 4200-319 Porto, Portugal; Morphysiology of the Somatosensory System Group, Instituto de Biologia Molecular e Celular (IBMC), Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Ferreira-Gomes
authors.affiliation: Departamento de Biologia Experimental, Centro de Investigação Médica da Faculdade de Medicina da Universidade do Porto (CIM-FMUP), Alameda Prof Hernâni Monteiro, 4200-319 Porto, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Mendonça
authors.affiliation: Departamento de Biologia Experimental, Centro de Investigação Médica da Faculdade de Medicina da Universidade do Porto (CIM-FMUP), Alameda Prof Hernâni Monteiro, 4200-319 Porto, Portugal.
authors.forename: L
authors.initials: L
authors.lastname: Almeida
authors.affiliation: Departamento de Biologia Experimental, Centro de Investigação Médica da Faculdade de Medicina da Universidade do Porto (CIM-FMUP), Alameda Prof Hernâni Monteiro, 4200-319 Porto, Portugal; Morphysiology of the Somatosensory System Group, Instituto de Biologia Molecular e Celular (IBMC), Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
authors.forename: J M
authors.initials: JM
authors.lastname: Castro-Lopes
authors.affiliation: Departamento de Biologia Experimental, Centro de Investigação Médica da Faculdade de Medicina da Universidade do Porto (CIM-FMUP), Alameda Prof Hernâni Monteiro, 4200-319 Porto, Portugal; Morphysiology of the Somatosensory System Group, Instituto de Biologia Molecular e Celular (IBMC), Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
authors.forename: F L
authors.initials: FL
authors.lastname: Neto
mesh_terms: D000588:Amines / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D015220:Calcium Channels / Q000378:metabolism; D020746:Calcium Channels, L-Type; D017364:Collagenases; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D000077206:Gabapentin; D005727:Ganglia, Spinal / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D059225:Nociception / Q000187:drug effects / Q000502:physiology; D059226:Nociceptive Pain / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D010003:Osteoarthritis / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000588:Amines; D000700:Analgesics; C486060:Cacna2d1 protein, rat; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D017364:Collagenases
keywords: Animal model; CatWalk; Knee-Bend; Movement-induced nociception; Neuronal injury