title: Nerve growth factor and associated nerve sprouting contribute to local mechanical hyperalgesia in a rat model of bone injury.
abstract: To clarify the mechanism of tenderness after bone injury, we investigated changes in the withdrawal threshold to mechanical stimuli, nerve distribution and nerve growth factor (NGF)-expression in a rat model of bone injury without immobilization for bone injury healing. Rats were divided into three groups as follows: (1) rats incised in the skin and periosteum, followed by drilling a hole in the tibia [bone lesion group (BLG)]; (2) those incised in the skin and periosteum without bone drilling [periosteum lesion group (PLG)]; and (3) those incised in the skin [skin lesion group (SLG)]. Mechanical hyperalgesia continued for 28 days at a lesion in the BLG, 21 days in PLG and 5 days in SLG after treatments, respectively. Endochondral ossification was observed on days 5-28 in BLG and on days 5-21 in PLG. Nerve growth appeared in deep connective tissue (DCT) at day 28 in BLG. Nerve fibres increased in both cutaneous tissue and DCT at day 7 in PLG, but they were not found at day 28. Mechanical hyperalgesia accompanied with endochondral ossification and nerve fibres increasing at the lesion in both BLG and PLG. NGF was expressed in bone-regenerating cells during the bone injury healing. Anti-NGF and trk inhibitor K252a inhibited hyperalgesia in the different time course. This study shows that localized tenderness coincides with the bone healing and involves NGF expression and nerve sprouting after bone injury. The findings present underlying mechanisms and provide pathophysiological relevance of local tenderness to determination of bone fracture and its healing.
authors.affiliation: Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yasui
authors.forename: Y
authors.initials: Y
authors.lastname: Shiraishi
authors.forename: N
authors.initials: N
authors.lastname: Ozaki
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Hori
authors.forename: M
authors.initials: M
authors.lastname: Ichiyanagi
authors.forename: Y
authors.initials: Y
authors.lastname: Sugiura
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism / Q000503:physiopathology; D002227:Carbazoles / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D050723:Fractures, Bone / Q000378:metabolism* / Q000503:physiopathology; D006930:Hyperalgesia / Q000378:metabolism* / Q000503:physiopathology; D026121:Indole Alkaloids / Q000494:pharmacology; D008297:Male; D009412:Nerve Fibers / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism*; D009999:Ossification, Heterotopic / Q000378:metabolism / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors; D013977:Tibia / Q000293:injuries* / Q000378:metabolism / Q000503:physiopathology; D014945:Wound Healing / Q000502:physiology
chemical_list: D057134:Antibodies, Neutralizing; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor; C049985:staurosporine aglycone