Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat

Sagar, Devi Rani; Nwosu, Lilian Ngozi; Walsh, David A.; Chapman, Victoria

doi:10.1016/j.joca.2015.01.010

Cited by 26 publications

(23 citation statements)

References 37 publications

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“…Secondary mechanical allodynia of the hind paw was not further reduced following IA NGF injection in OA rats (50). Supporting these findings, IA injection of NGF increased firing of spinal neurons in response to knee extension but not in response to noxious stimulation of the hind paw in MIA-injected rats (52). Together, these studies suggest that NGF may play a role in peripheral sensitization in OA.…”

Section: Peripheral Sensitizationmentioning

confidence: 76%

The Role of Peripheral Nociceptive Neurons in the Pathophysiology of Osteoarthritis Pain

Miller

Tran

Obeidat

et al. 2015

Curr Osteoporos Rep

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Knee osteoarthritis is characterized by progressive damage and remodeling of all tissues in the knee joint. Pain is the main symptom associated with knee osteoarthritis. Recent clinical and pre-clinical studies shed light on the mechanisms that drive the pain associated with joint destruction. In this narrative review, we describe current knowledge regarding the changes in the peripheral and central nervous system that occur during the progression of osteoarthritis and discuss how therapeutic interventions may provide pain relief.

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Section: Peripheral Sensitizationmentioning

confidence: 76%

The Role of Peripheral Nociceptive Neurons in the Pathophysiology of Osteoarthritis Pain

Miller

Tran

Obeidat

et al. 2015

Curr Osteoporos Rep

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“…It is unclear from the current study design whether these changes pre‐date the onset of symptoms or are a result of the symptoms, and it is, therefore, possible that this joint stiffening gait pattern may have contributed to the onset of symptoms and OA illness. In any case, this “stiffer” joint is likely less able to dissipate the repetitive loading, which may in turn contribute to further joint damage consistent with OA pain pathways …”

Section: Discussionmentioning

confidence: 99%

Asymptomatic and symptomatic individuals with the same radiographic evidence of knee osteoarthritis walk with different knee moments and muscle activity

2016

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There is an established discordance between the structural joint damage and clinical symptoms of knee osteoarthritis; however, there has been little investigation into the differences in joint level biomechanics and muscle activation patterns during gait between symptomatic and asymptomatic individuals with the same radiographic evidence of osteoarthritis. The objective of this study was to examine three-dimensional knee joint biomechanics and muscle activation differences during gait between asymptomatic and symptomatic individuals with radiographic knee osteoarthritis. A total of 54 asymptomatic and 59 symptomatic individuals with a Kellgren-Lawrence osteoarthritis radiographic grade of 2 underwent a comprehensive gait analysis to examine differences in the magnitude and patterns of the knee flexion angle, three-dimensional net resultant moments, and electromyography of the quadriceps, hamstrings, and gastrocnemii during over ground walking between the two groups. The symptomatic group walked with significantly higher overall magnitudes and less mid-stance unloading of the net resultant knee adduction moment, lower peak flexion moments, and higher lateral hamstrings and quadriceps activity during stance than the Asymptomatic group (p < 0.05, sex-adjusted analysis), with a trend (p = 0.07) toward greater transverse plane range of moment over stance. The differences found suggest a "stiffer" frontal and sagittal plane pattern with symptomatic individuals, but with more muscle activity and a trend toward more torsional loading in the transverse plane, which may have implications for shear loading of the joint. This is the first evidence of differences in three-dimensional knee joint biomechanics and muscle activation between asymptomatic and symptomatic individuals with the same radiographic grade. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1661-1670, 2017.

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“…Rats were killed by an overdose of carbon dioxide and tissues harvested at 20 days (1 mg; n = 18 and 0.1 mg MIA; n = 18) or 42 days (0.1 mg MIA; n = 10) post-injection. Previous studies indicated that OA pathology and pain behaviour were fully developed by 20 days after intra-articular injection of 1 mg MIA 17 . All outcome measurements were carried out by an experimenter blinded to intra-articular injections.…”

Section: Methodsmentioning

confidence: 99%

Relationship between structural pathology and pain behaviour in a model of osteoarthritis (OA)

Nwosu

Mapp

Chapman

et al. 2016

Osteoarthritis and Cartilage

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SummaryObjectivesTo address the hypothesis that different types of established osteoarthritis (OA) pain behaviours have associations with different aspects of articular pathology, we investigated the relationship between structural knee joint pathology and pain behaviour following injection of a low vs a high dose of monosodium iodoacetate (MIA) in the rat.MethodsRats received a single intra-articular injection of 0.1 mg or 1 mg MIA or saline (control). Pain behaviour (hind limb weight bearing asymmetry (WB) and hindpaw withdrawal threshold (PWT) to punctate stimulation) was assessed. Cartilage and synovium were examined by macroscopic visualisation of articular surfaces and histopathology.ResultsBoth doses of MIA lowered PWTs, 1 mg MIA also resulted in WB asymmetry. Both doses were associated with cartilage macroscopic appearance, proteoglycan loss, abnormal chondrocyte morphology, increased numbers of vessels crossing the osteochondral junction, synovitis and macrophage infiltration into the synovium. PWTs were more strongly associated with chondrocyte morphology, synovitis and macrophage infiltration than with loss of cartilage surface integrity.ConclusionsBoth pain behaviours were associated with OA structural severity and synovitis. Differences in pain phenotype following low vs higher dose of MIA were identified despite similar structural pathology. OA structural pathology as traditionally measured only partially explains the MIA-induced pain phenotype.

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Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat

Cited by 26 publications

References 37 publications

The Role of Peripheral Nociceptive Neurons in the Pathophysiology of Osteoarthritis Pain

The Role of Peripheral Nociceptive Neurons in the Pathophysiology of Osteoarthritis Pain

Asymptomatic and symptomatic individuals with the same radiographic evidence of knee osteoarthritis walk with different knee moments and muscle activity

Relationship between structural pathology and pain behaviour in a model of osteoarthritis (OA)

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