1. Calcitonin alleviates hyperalgesia in osteoporotic rats by modulating serotonin transporter activity.
- Author
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Yeh CB, Weng SJ, Chang KW, Chan JY, Huang SM, Chu TH, Wei NK, Ma HS, Cheng JT, Ma KH, Chen TH, and Shyu JF
- Subjects
- Alendronate pharmacology, Animals, Female, Ovariectomy, Random Allocation, Rats, Rats, Sprague-Dawley, Receptor, Serotonin, 5-HT1A, Calcitonin pharmacology, Hyperalgesia drug therapy, Osteoporosis drug therapy, Serotonin Plasma Membrane Transport Proteins metabolism
- Abstract
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.
- Published
- 2016
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