{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T05:47:42Z","timestamp":1769320062583,"version":"3.49.0"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2010characterized 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\u2010paw 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\u2010paw skin collected for PCR assays and paw skin Immunohistochemistry evaluation. Hindlimb loading reduced hind\u2010paw 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\u2010paw 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.<\/jats:p>","DOI":"10.1002\/jor.25750","type":"journal-article","created":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T04:25:13Z","timestamp":1701663913000},"page":"1020-1032","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Remission of hypersensitivity by simple weight load stimuli in a complex regional pain syndrome mouse model"],"prefix":"10.1002","volume":"42","author":[{"given":"Kenta","family":"Kiyomoto","sequence":"first","affiliation":[{"name":"Department of Musculoskeletal Anti\u2010aging Medicine Sapporo Medical University Sapporo Japan"},{"name":"Department of Orthopaedic Surgery Sapporo Medical University School of Medicine Sapporo Japan"},{"name":"Division of Occupational Therapy, Department of Rehabilitation, Faculty of Health Science Japan 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