High bone turnover state under osteoporotic changes induces pain-like behaviors in mild osteoarthritis model mice

Kiyomoto, Kenta; Iba, Kousuke; Hanaka, Megumi; Ibe, Koji; Hayakawa, Hikaru; Teramoto, Atsushi; Emori, Makoto; Yamashita, Toshihiko

doi:10.1007/s00774-020-01124-y

Cited by 7 publications

(3 citation statements)

References 33 publications

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“…On the other hand, we previously reported several studies focused on the relationship between transient receptor potential vanilloid 1 (TRPV1) and bone pain. [8][9][10][11][12] In those studies, we demonstrated that TRPV1 has important roles as a nociceptive sensor for increased pain-related molecules under pathophysiological conditions in bone tissue. We, therefore, focused on TRPV1 expression in the current CRPS mouse model in response to fracture and immobilization of limb in this study.…”

Section: Introductionmentioning

confidence: 89%

“…In particular, this method of physical therapy could afford a suitable tool for treating patients who avoid movement and functional use due to hypersensitivity. On the other hand, we previously reported several studies focused on the relationship between transient receptor potential vanilloid 1 (TRPV1) and bone pain 8–12 . In those studies, we demonstrated that TRPV1 has important roles as a nociceptive sensor for increased pain‐related molecules under pathophysiological conditions in bone tissue.…”

Section: Introductionmentioning

confidence: 96%

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Remission of hypersensitivity by simple weight load stimuli in a complex regional pain syndrome mouse model

Kiyomoto,

Emori,

Hanaka

et al. 2023

Journal Orthopaedic Research

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Painful sensitivity of the hand or foot are the most common and debilitating symptoms of complex regional pain syndrome (CRPS). Physical therapy is standard treatment for CRPS, but evidence supporting its efficacy is minimal and it can be essentially impossible for CRPS patients to actively exercise the painful limb. Using the well‐characterized distal tibial fracture CRPS mouse model, we compared the therapeutic effects of several weeks of daily hindlimb loading versus rotarod walking exercise. The effects of loading and exercise were evaluated by weekly testing of hind‐paw withdrawal thresholds to von Frey fibers and radiant heat, as well as measurements of paw and ankle edema. At 6 weeks after fracture, the mice were killed and the ipsilateral femur, spinal cord and L4/5 dorsal root ganglia, and hind‐paw skin collected for PCR assays and paw skin Immunohistochemistry evaluation. Hindlimb loading reduced hind‐paw von Frey allodynia and heat hyperalgesia and edema within a week and these effects persisted for at least a week after discontinuing treatment. These therapeutic effects of loading exceeded the beneficial effects observed with rotarod walking exercise in fracture mice. Levels of nerve growth factor and transient receptor potential vanilloid 1 (TRPV1) immunostaining in the hind‐paw skin were increased at 6 weeks after fracture, and both loading and exercise treatment reduced increases. Collectively, these results suggest that loading may be an effective and possibly curative treatment in CRPS patients with sensitivity in the affected limb.

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Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 96%

Remission of hypersensitivity by simple weight load stimuli in a complex regional pain syndrome mouse model

Kiyomoto,

Emori,

Hanaka

et al. 2023

Journal Orthopaedic Research

Self Cite

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“…This phenotypedependency has been demonstrated in pre-clinical research, where bisphosphonates are differentially effective in reducing pain and not only bone but also cartilage pathology in OA models with high versus low bone turnover. [106][107][108][109] Recently, clodronate (n=74) 110 and neridronate (n=64) 111 have been successfully used for the treatment of knee and hand OA, with an interesting efficacy on BMLs, although the sample sizes are small. An individual patient data meta-analysis for examining their efficacy in specific knee OA subtypes is still ongoing.…”

Section: Antiresorptive Drugs: Bisphosphonates and Denosumabmentioning

confidence: 99%

The Development of Disease-Modifying Therapies for Osteoarthritis (DMOADs): The Evidence to Date

Oo¹,

Little²,

Duong³

et al. 2021

DDDT

113

163

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Osteoarthritis (OA) is a complex heterogeneous articular disease with multiple joint tissue involvement of varying severity and no regulatory-agency-approved diseasemodifying drugs (DMOADs). In this review, we discuss the reasons necessitating the development of DMOADs for OA management, the classifications of clinical phenotypes or molecular/mechanistic endotypes from the viewpoint of targeted drug discovery, and then summarize the efficacy and safety profile of a range of targeted drugs in Phase 2 and 3 clinical trials directed to cartilage-driven, bone-driven, and inflammation-driven endotypes. Finally, we briefly put forward the reasons for failures in OA clinical trials and possible steps to overcome these barriers.

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Postoperative Bisphosphonates Use is Associated with Reduced Adverse Outcomes After Primary Total Joint Arthroplasty of Hip and Knee: A Nationwide Population-Based Cohort Study

Shih,

Tan,

Shen

et al. 2024

Calcif Tissue Int

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High bone turnover state under osteoporotic changes induces pain-like behaviors in mild osteoarthritis model mice

Cited by 7 publications

References 33 publications

Remission of hypersensitivity by simple weight load stimuli in a complex regional pain syndrome mouse model

Remission of hypersensitivity by simple weight load stimuli in a complex regional pain syndrome mouse model

The Development of Disease-Modifying Therapies for Osteoarthritis (DMOADs): The Evidence to Date

Postoperative Bisphosphonates Use is Associated with Reduced Adverse Outcomes After Primary Total Joint Arthroplasty of Hip and Knee: A Nationwide Population-Based Cohort Study

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