Capsaicin-sensitive sensory neurons contribute to the maintenance of trabecular bone integrity

Sarah C. Offley, Tian Zhi Guo, Tzuping Wei, J. David Clark, Hannes Vogel, Derek P. Lindsey, Christopher R. Jacobs, Wei Yao, Nancy E Lane, Wade S. Kingery

    Research output: Contribution to journalArticle

    107 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)257-267
    Number of pages11
    JournalJournal of Bone and Mineral Research
    Volume20
    Issue number2
    DOIs
    StatePublished - Feb 2005

    Fingerprint

    Capsaicin
    Sensory Receptor Cells
    Maintenance
    Bone and Bones
    Tibia
    Sciatic Nerve
    Substance P
    Calcitonin Gene-Related Peptide
    Femur
    Neurotransmitter Agents
    Body Weight
    Efferent Neurons
    Hindlimb Suspension
    Cancellous Bone
    Peroneal Nerve
    Weight-Bearing
    Osteoclasts
    Cellular Structures
    Therapeutics
    Locomotion

    Keywords

    • BMD
    • Bone
    • Calcitonin gene-related peptide
    • Capsaicin
    • Osteoporosis
    • Substance P

    ASJC Scopus subject areas

    • Surgery

    Cite this

    Offley, S. C., Guo, T. Z., Wei, T., Clark, J. D., Vogel, H., Lindsey, D. P., ... Kingery, W. S. (2005). Capsaicin-sensitive sensory neurons contribute to the maintenance of trabecular bone integrity. Journal of Bone and Mineral Research, 20(2), 257-267. https://doi.org/10.1359/JBMR.041108

    Capsaicin-sensitive sensory neurons contribute to the maintenance of trabecular bone integrity. / Offley, Sarah C.; Guo, Tian Zhi; Wei, Tzuping; Clark, J. David; Vogel, Hannes; Lindsey, Derek P.; Jacobs, Christopher R.; Yao, Wei; Lane, Nancy E; Kingery, Wade S.

    In: Journal of Bone and Mineral Research, Vol. 20, No. 2, 02.2005, p. 257-267.

    Research output: Contribution to journalArticle

    Offley, SC, Guo, TZ, Wei, T, Clark, JD, Vogel, H, Lindsey, DP, Jacobs, CR, Yao, W, Lane, NE & Kingery, WS 2005, 'Capsaicin-sensitive sensory neurons contribute to the maintenance of trabecular bone integrity', Journal of Bone and Mineral Research, vol. 20, no. 2, pp. 257-267. https://doi.org/10.1359/JBMR.041108
    Offley, Sarah C. ; Guo, Tian Zhi ; Wei, Tzuping ; Clark, J. David ; Vogel, Hannes ; Lindsey, Derek P. ; Jacobs, Christopher R. ; Yao, Wei ; Lane, Nancy E ; Kingery, Wade S. / Capsaicin-sensitive sensory neurons contribute to the maintenance of trabecular bone integrity. In: Journal of Bone and Mineral Research. 2005 ; Vol. 20, No. 2. pp. 257-267.
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    abstract = "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.",
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    AU - Vogel, Hannes

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