Wank, Isabel and Niedermair, Tanja and Kronenberg, Daniel and Stange, Richard and Brochhausen, Christoph and Hess, Andreas and Graessel, Susanne (2023) Influence of the Peripheral Nervous System on Murine Osteoporotic Fracture Healing and Fracture-Induced Hyperalgesia. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 (1): 510. ISSN , 1422-0067
Full text not available from this repository. (Request a copy)Abstract
Osteoporotic fractures are often linked to persisting chronic pain and poor healing outcomes. Substance P (SP), alpha-calcitonin gene-related peptide (alpha-CGRP) and sympathetic neurotransmitters are involved in bone remodeling after trauma and nociceptive processes, e.g., fracture-induced hyperalgesia. We aimed to link sensory and sympathetic signaling to fracture healing and fracture-induced hyperalgesia under osteoporotic conditions. Externally stabilized femoral fractures were set 28 days after OVX in wild type (WT), alpha-CGRP- deficient (alpha-CGRP -/-), SP-deficient (Tac1-/-) and sympathectomized (SYX) mice. Functional MRI (fMRI) was performed two days before and five and 21 days post fracture, followed by mu CT and biomechanical tests. Sympathectomy affected structural bone properties in the fracture callus whereas loss of sensory neurotransmitters affected trabecular structures in contralateral, non-fractured bones. Biomechanical properties were mostly similar in all groups. Both nociceptive and resting-state (RS) fMRI revealed significant baseline differences in functional connectivity (FC) between WT and neurotransmitter-deficient mice. The fracture-induced hyperalgesia modulated central nociception and had robust impact on RS FC in all groups. The changes demonstrated in RS FC in fMRI might potentially be used as a bone traumata-induced biomarker regarding fracture healing under pathophysiological musculoskeletal conditions. The findings are of clinical importance and relevance as they advance our understanding of pain during osteoporotic fracture healing and provide a potential imaging biomarker for fracture-related hyperalgesia and its temporal development. Overall, this may help to reduce the development of chronic pain after fracture thereby improving the treatment of osteoporotic fractures.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENE-RELATED PEPTIDE; RESTING-STATE NETWORKS; CEREBRAL-BLOOD-FLOW; SUBSTANCE-P; FUNCTIONAL CONNECTIVITY; BONE LOSS; DESCENDING CONTROL; INBRED STRAINS; PAIN; MICE; osteoporosis; fracture healing; bone-brain nervous system interactions; fMRI sensory and sympathetic nervous system |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Orthopädie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Mar 2024 14:46 |
| Last Modified: | 10 Mar 2024 14:47 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59607 |
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