Calcitonin alleviates hyperalgesia in osteoporotic rats by modulating serotonin transporter activity. Issue 11 (November 2016)

• Record Type: Journal Article
• Authors: Yeh, C.-B.; Weng, S.-J.; Chang, K.-W.; Chan, J.; Huang, S.-M.; Chu, T.-H.; Wei, N.-K.; Ma, H.-S.; Cheng, J.-T.; Ma, K.-H.; Chen, T.-H.; Shyu, J.-F.
• Is Part Of: Osteoporosis international. Volume 27:Issue 11(2016)
• Page Start: 3355
• Page End: 3364
• Publication Date: 2016-11
• Subjects: Alendronate -- Calcitonin -- Hyperalgesia -- Osteoporosis -- Serotonin transporter; Osteoporosis -- Periodicals; Bones -- Metabolism -- Disorders -- Periodicals; 616.716005
• DOI: 10.1007/s00198-016-3652-1
• Languages: English
• ISSNs: 0937-941X

Abstract

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.