Calcitonin alleviates hyperalgesia in osteoporotic rats by modulating serotonin transporter activity.
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.



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.



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.



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.



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.
Department of Psychiatry, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan.
C-B
CB
Yeh
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
SJ
Weng
Atomic Energy Council, Executive Yuan, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
K-W
KW
Chang
Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan.
J Y-H
JY
Chan
Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
S-M
SM
Huang
Department of Biology and Anatomy, National Defense Medical Center, 161 Ming Chuan E. Road Section 6, Taipei, Taiwan, 114, People's Republic of China.
T-H
TH
Chu
Department of Biology and Anatomy, National Defense Medical Center, 161 Ming Chuan E. Road Section 6, Taipei, Taiwan, 114, People's Republic of China.
N-K
NK
Wei
Department of Biology and Anatomy, National Defense Medical Center, 161 Ming Chuan E. Road Section 6, Taipei, Taiwan, 114, People's Republic of China.
H-S
HS
Ma
Department of Biology and Anatomy, National Defense Medical Center, 161 Ming Chuan E. Road Section 6, Taipei, Taiwan, 114, People's Republic of China.
J-T
JT
Cheng
Department of Biology and Anatomy, National Defense Medical Center, 161 Ming Chuan E. Road Section 6, Taipei, Taiwan, 114, People's Republic of China.
K-H
KH
Ma
School of Medicine, Institute of Anatomy and Cell Biology, National Yang Ming University, Taipei, Taiwan.|Department of Surgery, Veteran General Hospital, Taipei, Taiwan.
T-H
TH
Chen
Department of Biology and Anatomy, National Defense Medical Center, 161 Ming Chuan E. Road Section 6, Taipei, Taiwan, 114, People's Republic of China. shyujeff@ndmctsgh.edu.tw.
J-F
JF
Shyu
D019386:Alendronate / Q000494:pharmacology; D000818:Animals; D002116:Calcitonin / Q000494:pharmacology*; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy*; D010024:Osteoporosis / Q000188:drug therapy*; D010052:Ovariectomy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*
D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; D002116:Calcitonin; D019386:Alendronate
Alendronate; Calcitonin; Hyperalgesia; Osteoporosis; Serotonin transporter