Blocking the tropomyosin receptor kinase A (TrkA) receptor inhibits pain behaviour in two rat models of osteoarthritis.
Ann Rheum Dis
; 75(6): 1246-54, 2016 06.
Article
en En
| MEDLINE
| ID: mdl-26286016
ABSTRACT
OBJECTIVES:
Tropomyosin receptor kinase A (TrkA) mediates nociceptor sensitisation by nerve growth factor (NGF), but it is unknown whether selective TrkA inhibition will be an effective strategy for treating osteoarthritis (OA) pain. We determined the effects of a TrkA inhibitor (AR786) on pain behaviour, synovitis and joint pathology in two rat OA models.METHODS:
Knee OA was induced in rats by intra-articular monosodium-iodoacetate (MIA) injection or meniscal transection (MNX) and compared with saline-injected or sham-operated controls. Pain behaviour was assessed as weight-bearing asymmetry and paw withdrawal threshold to punctate stimulation. Oral doses (30â mg/kg) of AR786 or vehicle were administered twice daily in either preventive (day -1 to -27) or treatment (day 14-28) protocols. Effect maintenance was evaluated for 2â weeks after treatment discontinuation. Alterations in knee structure (cartilage, subchondral bone and synovium) were examined by macroscopic visualisation of articular surfaces and histopathology.RESULTS:
Preventive AR786 treatment inhibited pain behaviour development and therapeutic treatment attenuated established pain behaviour. Weight-bearing asymmetry increased 1â week after treatment discontinuation, but remained less than in vehicle-treated arthritic rats, whereas paw withdrawal thresholds returned to levels of untreated rats within 5â days of treatment discontinuation. AR786 treatment reduced MIA-induced synovitis and did not significantly affect osteochondral pathology in either model.CONCLUSIONS:
Blocking NGF activity by inhibiting TrkA reduced pain behaviour in two rat models of OA. Analgesia was observed both using preventive and treatment protocols, and was sustained after treatment discontinuation. Selective inhibitors of TrkA therefore hold potential for OA pain relief.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Osteoartritis
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Dolor
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Artritis Experimental
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Analgésicos no Narcóticos
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Receptor trkA
Tipo de estudio:
Etiology_studies
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Guideline
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Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Ann Rheum Dis
Año:
2016
Tipo del documento:
Article
País de afiliación:
Reino Unido