Capsaicin-Sensitive Sensory Neurons Contribute to the Maintenance of Trabecular Bone Integrity
| Autor: | Nancy E Lane, Sarah C Offley, J. David Clark, Wade S. Kingery, Tian Zhi Guo, Hannes Vogel, Christopher R. Jacobs, Wei Yao, Tzuping Wei, Derek P. Lindsey |
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| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Bone density Calcitonin Gene-Related Peptide Endocrinology Diabetes and Metabolism Osteoporosis Osteoclasts Neuropeptide Substance P Bone and Bones Immunoenzyme Techniques Rats Sprague-Dawley chemistry.chemical_compound Absorptiometry Photon Bone Density Osteoclast Internal medicine medicine Animals Orthopedics and Sports Medicine Muscle Skeletal Neurons Neurotransmitter Agents Tibia Reverse Transcriptase Polymerase Chain Reaction business.industry Body Weight Osteoblast Organ Size medicine.disease Axons Sensory neuron Rats Microscopy Electron Endocrinology medicine.anatomical_structure chemistry Capsaicin Sciatic nerve Tomography X-Ray Computed business Signal Transduction |
| Zdroj: | Journal of Bone and Mineral Research. 20:257-267 |
| ISSN: | 0884-0431 |
| DOI: | 10.1359/jbmr.041108 |
| Popis: | This investigation used capsaicin to selectively lesion unmyelinated sensory neurons in rats. Neuronal lesioning induced a loss of trabecular integrity, reduced bone mass and strength, and depleted neuropeptides in nerve and bone. These data suggest that capsaicin-sensitive sensory nerves contribute to trabecular bone integrity. Introduction: Familial dysautomia is an autosomal recessive disease in which patients suffer from unmyelinated sensory neuron loss, reduced BMD, and frequent fractures. It has been proposed that the loss of neurotransmitters synthesized by unmyelinated neurons adversely affects bone integrity in this hereditary syndrome. The purpose of this study was to determine whether small sensory neurons are required for the maintenance of bone integrity in rats. Materials and Methods: Ten-month-old male Sprague-Dawley rats were treated with either capsaicin or vehicle. In vivo DXA scanning and μCT scanning, and histomorphometry were used to evaluate BMD, structure, and cellular activity. Bone strength was measured in distal femoral sections. Body weight and gastrocnemius/soleus weights were measured and spontaneous locomotor activity was monitored. Peroneal nerve morphometry was evaluated using light and electron microscopy. Substance P and calcitonin gene-related peptide (CGRP) content in the sciatic nerve and proximal tibia were determined by enzyme immunoassay (EIA). Substance P signaling was measured using a sciatic nerve stimulation extravasation assay. Results: Four weeks after capsaicin treatment, there was a loss of BMD in the metaphyses of the tibia and femur. In the proximal tibia, the osteoclast number and surface increased, osteoblast activity and bone formation were impaired, and trabecular bone volume and connectivity were diminished. There was also a loss of bone strength in the distal femur. No changes occurred in body weight, 24-h grid-crossing activity, weight bearing, or muscle mass after capsaicin treatment, indicating that skeletal unloading did not contribute to the loss of bone integrity. Capsaicin treatment destroyed 57% of the unmyelinated sensory axons, reduced the substance P and CGRP content in the sciatic nerve and proximal tibia, and inhibited neurogenic extravasation. Conclusion: These results support the hypothesis that capsaicin-sensitive sensory neurons contribute to the maintenance of trabecular bone integrity. Capsaicin-sensitive neurons have efferent functions in the tissues they innervate, effects mediated by transmitters released from the peripheral nerve terminals. We postulate that the deleterious effects of capsaicin treatment on trabecular bone are mediated by reductions in local neurotransmitter content and release. |
| Databáze: | OpenAIRE |
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