Show simple item record

dc.contributor.authorWalsh, David A
dc.date.accessioned2021-12-01T15:13:33Z
dc.date.available2021-12-01T15:13:33Z
dc.date.issued2016-06
dc.identifier.citationNwosu, L. N. et al. (2016) ‘Blocking the tropomyosin receptor kinase A (TrkA) receptor inhibits pain behaviour in two rat models of osteoarthritis’, Annals of the Rheumatic Diseases, 75(6), pp. 1246–1254en_US
dc.identifier.urihttp://hdl.handle.net/20.500.12904/15000
dc.description.abstractObjectives: 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 (30 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 2 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 1 week after treatment discontinuation, but remained less than in vehicle-treated arthritic rats, whereas paw withdrawal thresholds returned to levels of untreated rats within 5 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.
dc.description.urihttps://ard.bmj.com/content/75/6/1246.longen_US
dc.publisherAnnals of the Rheumatic Diseasesen_US
dc.subjectAnalgesicsen_US
dc.subjectKnee osteoarthritisen_US
dc.subjectSynovitisen_US
dc.subjectTreatmenten_US
dc.titleBlocking the Tropomyosin receptor kinase A (TrkA) receptor inhibits pain behaviour in two rat models of osteoarthritisen_US
dc.typeArticleen_US
rioxxterms.funderDefault funderen_US
rioxxterms.identifier.projectDefault projecten_US
rioxxterms.versionNAen_US
rioxxterms.versionofrecord10.1136/annrheumdis-2014-207203en_US
rioxxterms.typeJournal Article/Reviewen_US
refterms.dateFOA2021-12-01T15:13:34Z
refterms.panelUnspecifieden_US
refterms.dateFirstOnline2015-08
html.description.abstractObjectives: 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 (30 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 2 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 1 week after treatment discontinuation, but remained less than in vehicle-treated arthritic rats, whereas paw withdrawal thresholds returned to levels of untreated rats within 5 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.en_US
rioxxterms.funder.project94a427429a5bcfef7dd04c33360d80cden_US


Files in this item

Thumbnail
Name:
Blocking the Tropomyosin receptor ...
Size:
1.347Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record