Augmented pain behavioural responses to intra-articular injection of nerve growth factor in two animal models of osteoarthritis

Sadaf Ashraf, Paul Ian Mapp, James Burston, Andrew John Bennett, Victoria Chapman, David Andrew Walsh (Corresponding Author)

Research output: Contribution to journalArticle

45 Citations (Scopus)
4 Downloads (Pure)

Abstract

OBJECTIVES: Nerve growth factor (NGF) is a promising analgesic target, particularly in osteoarthritis (OA) where existing therapies are inadequate. We hypothesised that pain responses to NGF are increased in OA joints. Here, NGF-evoked pain behaviour was compared in two rodent models of OA, and possible mechanisms underlying altered pain responses were examined.

METHODS: OA was induced in rat knees by meniscal transection (MNX) or intra-articular monosodium iodoacetate injection (MIA). Once OA pathology was fully established (day 20), we assessed pain behaviour (hindlimb weight-bearing asymmetry and hindpaw mechanical withdrawal thresholds) evoked by intra-articular injection of NGF (10 µg). Possible mechanisms underlying alterations in NGF-induced pain behaviour were explored using indomethacin pretreatment, histopathological evaluation of synovitis, and rtPCR for NGF receptor (tropomyosin receptor kinase (Trk)-A) expression in dorsal root ganglia (DRG).

RESULTS: Both the MIA and MNX models of OA displayed reduced ipsilateral weight bearing and hindpaw mechanical withdrawal thresholds, mild synovitis and increased TrkA expression in DRG. NGF injection into OA knees produced a prolonged augmentation of weight-bearing asymmetry, compared to NGF injection in non-osteoarthritic knees. However, hindpaw mechanical withdrawal thresholds were not further decreased by NGF. Pretreatment with indomethacin attenuated NGF-facilitated weight-bearing asymmetry and reversed OA-induced ipsilateral TrkA mRNA up-regulation.

CONCLUSIONS: OA knees were more sensitive to NGF-induced pain behaviour compared to non-osteoarthritic knees. Cyclo-oxygenase products may contribute to increased TrkA expression during OA development, and the subsequent increased NGF sensitivity. Treatments that reduce sensitivity to NGF have potential to improve OA pain.

Original languageEnglish
Pages (from-to)1710-1718
Number of pages9
JournalAnnals of the Rheumatic Diseases
Volume73
Issue number9
Early online date13 Jul 2013
DOIs
Publication statusPublished - Sep 2014

Fingerprint

Intra-Articular Injections
Nerve Growth Factor
Osteoarthritis
Animals
Animal Models
Pain
Bearings (structural)
Weight-Bearing
Iodoacetates
Knee
Injections
Synovitis
Knee Osteoarthritis
Spinal Ganglia
Indomethacin
Joints
Nerve Growth Factor Receptor
Tropomyosin
Pathology
Hindlimb

Cite this

Augmented pain behavioural responses to intra-articular injection of nerve growth factor in two animal models of osteoarthritis. / Ashraf, Sadaf; Mapp, Paul Ian; Burston, James; Bennett, Andrew John; Chapman, Victoria; Walsh, David Andrew (Corresponding Author).

In: Annals of the Rheumatic Diseases, Vol. 73, No. 9, 09.2014, p. 1710-1718.

Research output: Contribution to journalArticle

Ashraf, Sadaf ; Mapp, Paul Ian ; Burston, James ; Bennett, Andrew John ; Chapman, Victoria ; Walsh, David Andrew. / Augmented pain behavioural responses to intra-articular injection of nerve growth factor in two animal models of osteoarthritis. In: Annals of the Rheumatic Diseases. 2014 ; Vol. 73, No. 9. pp. 1710-1718.
@article{30668a23fa1d48518603fd4abaa28bb4,
title = "Augmented pain behavioural responses to intra-articular injection of nerve growth factor in two animal models of osteoarthritis",
abstract = "OBJECTIVES: Nerve growth factor (NGF) is a promising analgesic target, particularly in osteoarthritis (OA) where existing therapies are inadequate. We hypothesised that pain responses to NGF are increased in OA joints. Here, NGF-evoked pain behaviour was compared in two rodent models of OA, and possible mechanisms underlying altered pain responses were examined.METHODS: OA was induced in rat knees by meniscal transection (MNX) or intra-articular monosodium iodoacetate injection (MIA). Once OA pathology was fully established (day 20), we assessed pain behaviour (hindlimb weight-bearing asymmetry and hindpaw mechanical withdrawal thresholds) evoked by intra-articular injection of NGF (10 µg). Possible mechanisms underlying alterations in NGF-induced pain behaviour were explored using indomethacin pretreatment, histopathological evaluation of synovitis, and rtPCR for NGF receptor (tropomyosin receptor kinase (Trk)-A) expression in dorsal root ganglia (DRG).RESULTS: Both the MIA and MNX models of OA displayed reduced ipsilateral weight bearing and hindpaw mechanical withdrawal thresholds, mild synovitis and increased TrkA expression in DRG. NGF injection into OA knees produced a prolonged augmentation of weight-bearing asymmetry, compared to NGF injection in non-osteoarthritic knees. However, hindpaw mechanical withdrawal thresholds were not further decreased by NGF. Pretreatment with indomethacin attenuated NGF-facilitated weight-bearing asymmetry and reversed OA-induced ipsilateral TrkA mRNA up-regulation.CONCLUSIONS: OA knees were more sensitive to NGF-induced pain behaviour compared to non-osteoarthritic knees. Cyclo-oxygenase products may contribute to increased TrkA expression during OA development, and the subsequent increased NGF sensitivity. Treatments that reduce sensitivity to NGF have potential to improve OA pain.",
author = "Sadaf Ashraf and Mapp, {Paul Ian} and James Burston and Bennett, {Andrew John} and Victoria Chapman and Walsh, {David Andrew}",
note = "Acknowledgements The authors would like to thank Paul Millns for his technical assistance with tissue (dorsal root ganglia) collection. Competing interests None. Provenance and peer review Not commissioned; externally peer reviewed",
year = "2014",
month = "9",
doi = "10.1136/annrheumdis-2013-203416",
language = "English",
volume = "73",
pages = "1710--1718",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",
number = "9",

}

TY - JOUR

T1 - Augmented pain behavioural responses to intra-articular injection of nerve growth factor in two animal models of osteoarthritis

AU - Ashraf, Sadaf

AU - Mapp, Paul Ian

AU - Burston, James

AU - Bennett, Andrew John

AU - Chapman, Victoria

AU - Walsh, David Andrew

N1 - Acknowledgements The authors would like to thank Paul Millns for his technical assistance with tissue (dorsal root ganglia) collection. Competing interests None. Provenance and peer review Not commissioned; externally peer reviewed

PY - 2014/9

Y1 - 2014/9

N2 - OBJECTIVES: Nerve growth factor (NGF) is a promising analgesic target, particularly in osteoarthritis (OA) where existing therapies are inadequate. We hypothesised that pain responses to NGF are increased in OA joints. Here, NGF-evoked pain behaviour was compared in two rodent models of OA, and possible mechanisms underlying altered pain responses were examined.METHODS: OA was induced in rat knees by meniscal transection (MNX) or intra-articular monosodium iodoacetate injection (MIA). Once OA pathology was fully established (day 20), we assessed pain behaviour (hindlimb weight-bearing asymmetry and hindpaw mechanical withdrawal thresholds) evoked by intra-articular injection of NGF (10 µg). Possible mechanisms underlying alterations in NGF-induced pain behaviour were explored using indomethacin pretreatment, histopathological evaluation of synovitis, and rtPCR for NGF receptor (tropomyosin receptor kinase (Trk)-A) expression in dorsal root ganglia (DRG).RESULTS: Both the MIA and MNX models of OA displayed reduced ipsilateral weight bearing and hindpaw mechanical withdrawal thresholds, mild synovitis and increased TrkA expression in DRG. NGF injection into OA knees produced a prolonged augmentation of weight-bearing asymmetry, compared to NGF injection in non-osteoarthritic knees. However, hindpaw mechanical withdrawal thresholds were not further decreased by NGF. Pretreatment with indomethacin attenuated NGF-facilitated weight-bearing asymmetry and reversed OA-induced ipsilateral TrkA mRNA up-regulation.CONCLUSIONS: OA knees were more sensitive to NGF-induced pain behaviour compared to non-osteoarthritic knees. Cyclo-oxygenase products may contribute to increased TrkA expression during OA development, and the subsequent increased NGF sensitivity. Treatments that reduce sensitivity to NGF have potential to improve OA pain.

AB - OBJECTIVES: Nerve growth factor (NGF) is a promising analgesic target, particularly in osteoarthritis (OA) where existing therapies are inadequate. We hypothesised that pain responses to NGF are increased in OA joints. Here, NGF-evoked pain behaviour was compared in two rodent models of OA, and possible mechanisms underlying altered pain responses were examined.METHODS: OA was induced in rat knees by meniscal transection (MNX) or intra-articular monosodium iodoacetate injection (MIA). Once OA pathology was fully established (day 20), we assessed pain behaviour (hindlimb weight-bearing asymmetry and hindpaw mechanical withdrawal thresholds) evoked by intra-articular injection of NGF (10 µg). Possible mechanisms underlying alterations in NGF-induced pain behaviour were explored using indomethacin pretreatment, histopathological evaluation of synovitis, and rtPCR for NGF receptor (tropomyosin receptor kinase (Trk)-A) expression in dorsal root ganglia (DRG).RESULTS: Both the MIA and MNX models of OA displayed reduced ipsilateral weight bearing and hindpaw mechanical withdrawal thresholds, mild synovitis and increased TrkA expression in DRG. NGF injection into OA knees produced a prolonged augmentation of weight-bearing asymmetry, compared to NGF injection in non-osteoarthritic knees. However, hindpaw mechanical withdrawal thresholds were not further decreased by NGF. Pretreatment with indomethacin attenuated NGF-facilitated weight-bearing asymmetry and reversed OA-induced ipsilateral TrkA mRNA up-regulation.CONCLUSIONS: OA knees were more sensitive to NGF-induced pain behaviour compared to non-osteoarthritic knees. Cyclo-oxygenase products may contribute to increased TrkA expression during OA development, and the subsequent increased NGF sensitivity. Treatments that reduce sensitivity to NGF have potential to improve OA pain.

U2 - 10.1136/annrheumdis-2013-203416

DO - 10.1136/annrheumdis-2013-203416

M3 - Article

VL - 73

SP - 1710

EP - 1718

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 9

ER -