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Calcitonin alleviates hyperalgesia in osteoporotic rats by modulating serotonin transporter activity

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Abstract

Summary

Calcitonin may relieve pain by modulating central serotonin activity. Calcitonin partly reversed the hypersensitivity to pain induced by ovariectomy. This suggests that the anti-nociceptive effects of calcitonin in the treatment of osteoporosis may be mediated by alterations in neural serotonin transporter (SERT) activity.

Introduction

This study used a rat model of osteoporosis to evaluate the role of the cerebral serotonin system in the anti-nociceptive effect of calcitonin, a drug used to treat post-menopausal osteoporosis.

Methods

Osteoporosis was induced in rats by ovariectomy (OVX). Rats were then randomized to the following four groups: sham operation, OVX, OVX plus calcitonin, or OVX plus alendronate.

Results

OVX led to alterations in bone micro-architecture; alendronate strongly reversed this effect, and calcitonin moderately reversed this effect. OVX increased hyperalgesia (determined as the time for hind paw withdrawal from a heat source); calcitonin reduced this effect, but alendronate had no effect. OVX increased the expression of c-Fos (a neuronal marker of pain) in the thalamus; calcitonin strongly reversed this effect, and alendronate moderately reversed this effect. OVX also reduced SERT but increased 5-HT1A receptor expression and activity; calcitonin aggravated this effect, but alendronate had no effect on recovery of SERT/5-HT1A activity and expression.

Conclusions

Our study of a rat model of osteoporosis suggests that OVX-induced enhancement of the serotonergic system may protect against hyperalgesia. However, the anti-nociceptive effects of calcitonin in osteoporosis may be mediated by decreased neural SERT activity and increased activation of 5-HT1 receptors in the thalamus.

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Acknowledgments

This research was partly supported by research grants to J.-F. Shyu from the National Defense Medical Center (MAB-102-56), the Tri-Service General Hospital (TSGH-C102-124), and the Ministry of Science and Technology (MOST 104-2320-B-016-008) of Taiwan.

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Authors and Affiliations

  1. Department of Psychiatry, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan

    C.-B. Yeh

  2. Department of Biology and Anatomy, National Defense Medical Center, 161 Ming Chuan E. Road Section 6, Taipei, Taiwan, 114, People’s Republic of China

    S.-J. Weng, T.-H. Chu, N.-K. Wei, H.-S. Ma, J.-T. Cheng, K.-H. Ma & J.-F. Shyu

  3. Atomic Energy Council, Executive Yuan, Institute of Nuclear Energy Research, Taoyuan, Taiwan

    K.-W. Chang

  4. Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan

    J. Y.-H. Chan

  5. Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan

    S.-M. Huang

  6. School of Medicine, Institute of Anatomy and Cell Biology, National Yang Ming University, Taipei, Taiwan

    T.-H. Chen

  7. Department of Surgery, Veteran General Hospital, Taipei, Taiwan

    T.-H. Chen

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  1. C.-B. Yeh
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  2. S.-J. Weng
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Correspondence to J.-F. Shyu.

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Yeh, CB., Weng, SJ., Chang, KW. et al. Calcitonin alleviates hyperalgesia in osteoporotic rats by modulating serotonin transporter activity. Osteoporos Int 27, 3355–3364 (2016). https://doi.org/10.1007/s00198-016-3652-1

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  • DOI: https://doi.org/10.1007/s00198-016-3652-1

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