Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs

Minnema, Laura; Wheeler, Joshua J.; Enomoto, Masataka; Pitake, Saumitra; Mishra, Santosh K.; Lascelles, B. Duncan X.

doi:10.3389/fnins.2020.00077

Cited by 21 publications

(25 citation statements)

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“…The medical approach to OA aims at slowing disease progression, relieving pain, and improving overall function ( 14 , 24 ), and it is well suited to be addressed through the use of local therapy by intra-articular (IA) injection ( 25 , 26 ). IA corticosteroids have been used for several decades.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Intra-articular Injections With Either Triamcinolone Hexacetonide, Stanozolol, Hylan G-F 20, or a Platelet Concentrate Improve Clinical Signs in Police Working Dogs With Bilateral Hip Osteoarthritis

Alves

Santos²,

Jorge³

et al. 2021

Front. Vet. Sci.

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Objectives: To compare the effect of intra-articular treatment with triamcinolone hexacetonide (TH), stanozolol, hyaluronan, and a platelet concentrate in police working dogs with bilateral hip osteoarthritis (OA).Study Design: Prospective, longitudinal, double-blinded, negative controlled study.Sample Population: Fifty police working dogs with naturally occurring hip OA.Methods: Animals were randomly assigned to a control group (CG, n = 10), TH group (THG, n = 10), platelet concentrate group (PCG, n = 10), stanozolol group (SG, n = 10), and Hylan G-F 20 group (HG). On days 0 (T0), 8, 15, 30, 90, and 180 days post-treatment, weight-bearing distribution was evaluated. In those days, and on days 60, 120, and 150, four clinical metrology instruments were completed. Kaplan–Meier estimators were conducted and compared with the log-rank test. Cox proportional hazard regression analysis was performed to determine treatment survival. Significance was set at p < 0.05.Results: Patients had a mean age of 6.5 ± 2.4 years and body weight of 26.7 ± 5.2 kg. At T0, hips were classified as mild (n = 35), moderate (n = 10), and severe (n = 5), according to the Orthopedic Foundation for Animals grading scheme. No differences were found between groups at that moment considering age, body weight, OFA hip score, and all assessments performed. All treatments improved clinical signs in various OA dimensions in some groups, with a broad effect interval. PCG showed a lower range of variation while maintaining a positive result for more extended periods (p < 0.01 for symmetry index and 0.01 < p < 0.04 in the majority of scores). Breed, age, sex, and OFA grade did not significantly influence response to treatment.Conclusions and Clinical Relevance: This is the first prospective, negative controlled, double-blinded study to compare the effect of a single administration of these IA treatments in dogs with hip OA. HG and PCG recorded more significant improvements throughout the 180-day follow-up. In particular, PCG also registered a lower variation in results, seemingly the best therapeutic option. Nevertheless, improvements were still observed in THG and SG, and these treatment options can be considered, mainly when the first two treatments are not available.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Intra-articular Injections With Either Triamcinolone Hexacetonide, Stanozolol, Hylan G-F 20, or a Platelet Concentrate Improve Clinical Signs in Police Working Dogs With Bilateral Hip Osteoarthritis

Alves

Santos²,

Jorge³

et al. 2021

Front. Vet. Sci.

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“…The medical approach to OA aims at slowing disease progression while relieving symptoms, particularly pain [ 9 , 12 ]. IA corticosteroids have been used for several decades to palliate pain and inflammation associated with OA and of joint’s surrounding tissues [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

The intra-articular administration of triamcinolone hexacetonide in the treatment of osteoarthritis. Its effects in a naturally occurring canine osteoarthritis model

Alves

Santos²,

Jorge³

et al. 2021

PLoS ONE

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Objective To evaluate the effect of an intra-articular (IA) administration of triamcinolone hexacetonide, compared with saline. Patients and methods Forty (N = 40) hip joints were randomly assigned to a treatment group (THG, n = 20, receiving IA triamcinolone hexacetonide) and a control group (CG, n = 20, receiving IA saline). On treatment day (T0), and at 8, 15, 30, 90 and 180 days post-treatment, weight distribution, joint range of motion, thigh girth, digital thermography, radiographic signs, synovial fluid interleukin-1 and C-reactive protein levels were evaluated. Data from four Clinical Metrology Instruments was also gathered. Results were compared Repeated Measures ANOVA, with a Huynh-Feldt correction, Paired Samples T-Test or Wilcoxon Signed Ranks Test. A Kaplan-Meier test was performed to compare both groups, with p<0.05. Results Joints were graded as mild (65%), moderate (20%) and severe (15%). Patients of both sexes, with a mean age of 6.5±2.4 years and bodyweight of 26.7±5.2kg, were included. No differences were found between groups at T0. Comparing THG to CG, weight distribution showed significant improvements in THG from 8 (p = 0.05) up to 90 days (p = 0.01). THG showed lower values during thermographic evaluation in the Lt view (p<0.01). Pain and function scores also improved from 30 to 180 days. Increasing body weight, age, and presence of caudolateral curvilinear osteophyte corresponded to worse response to treatment. Results of the Kaplan Meier test showed significant differences between groups, with THG performing better considering several evaluations and scores. Conclusion THG recorded significant improvements in weight-bearing and in with the considered CMIs, particularly pain scores. Lower thermographic values were registered in THG up to the last evaluation day. Age, sex, and radiographic findings did significantly influenced response to treatment.

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“…Recently, we showed an increase in the expression of GFRα3 in the DRG of naturally occurring osteoarthritic dogs (11). Here, we sought to determine whether the same change held for the MIA-model of OA in mice.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, we found an elevated serum level of artemin in humans and dogs with naturally occurring OA (11). Further, we found significantly increased GFRα3 and transient receptor potential vanilloid (TRPV) subfamily-1 receptor expression in dogs DRG serving osteoarthritic joints compared to healthy dogs.…”

Section: Introductionmentioning

confidence: 99%

Artemin and its cognate receptor, GFRα3, play a function role in osteoarthritis pain

Minnema

Mishra

Lascelles

2020

Preprint

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Osteoarthritis associated pain (OA-pain) is a significant global problem. OA-pain limits limb use and mobility, and is associated with widespread sensitivity. Therapeutic options are limited, and the ones that are available are often associated with side or adverse effects. The lack of therapeutic options is partly due to a lack of understanding of clinically relevant underlying neural mechanisms of OA-pain. In previous work in naturally occurring OA-pain in dogs, we identified potential signaling molecules (artemin/GFRα3) that were upregulated. Here, we use multiple approaches including knockout mice, immunological suppression in a mouse model of OA, and clinically relevant measures of sensitivity and limb use to explore the functional role of artemin/GFRα3 signaling in OA-pain. We found the monoiodoacetate (MIA)-induced OA model in mice is associated with decreased limb use and hypersensitivity. GFRα3 expression is increased in sensory neurons. Exogenous artemin induces heat, cold and mechanical hypersensitivity, and anti-artemin monoclonal antibody administration reverses this hypersensitivity and restores limb use in mice with MIA-induced OA pain. Our results provide a molecular basis of arthritis pain linked with artemin/GFRα3 signaling and indicate that further work is warranted to investigate the neuronal plasticity and the pathways that drive pain in OA.

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Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs

Cited by 21 publications

References 50 publications

RETRACTED: Intra-articular Injections With Either Triamcinolone Hexacetonide, Stanozolol, Hylan G-F 20, or a Platelet Concentrate Improve Clinical Signs in Police Working Dogs With Bilateral Hip Osteoarthritis

RETRACTED: Intra-articular Injections With Either Triamcinolone Hexacetonide, Stanozolol, Hylan G-F 20, or a Platelet Concentrate Improve Clinical Signs in Police Working Dogs With Bilateral Hip Osteoarthritis

The intra-articular administration of triamcinolone hexacetonide in the treatment of osteoarthritis. Its effects in a naturally occurring canine osteoarthritis model

Artemin and its cognate receptor, GFRα3, play a function role in osteoarthritis pain

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