An immunohistochemical study of the antinociceptive effect of calcitonin in ovariectomized rats.
BACKGROUND
Calcitonin is used as a treatment to reduce the blood calcium concentration in hypercalcemia and to improve bone mass in osteoporosis. An analgesic effect of calcitonin has been observed and reported in clinical situations. Ovariectomized (OVX) rats exhibit the same hormonal changes as observed in humans with osteoporosis and are an animal model of postmenopausal osteoporosis. The aim of this study to investigate antinociceptive effect of calcitonin in OVX rats using the immunohistochemical study.


METHODS
We assessed the antinociceptive effects of calcitonin in an ovariectomized (OVX) rat model, which exhibit osteoporosis and hyperalgesia, using the immunohistochemical method. Fifteen rats were ovariectomized bilaterally, and ten rats were received the same surgery expected for ovariectomy as a sham model. We used five groups: the OVX-CT (n = 5), the sham-CT (n = 5), and the OVX-CT-pcpa (n = 5) groups received calcitonin (CT: 4 U/kg/day), while OVX-vehi (n = 5) and the sham-vehi (n = 5) groups received vehicle subcutaneously 5 times a week for 4 weeks. The OVX-CT-pcpa-group was given traperitoneal injection of p-chlorophenylalanine (pcpa; an inhibitor of serotonin biosynthesis) (100 mg/kg/day) in the last 3 days of calcitonin injection. Two hours after 5% formalin (0.05 ml) subcutaneously into the hind paw, the L5 spinal cord were removed and the number of Fos-immunoreactive (ir) neurons were evaluated using the Mann-Whitney-U test.


RESULTS
The numbers of Fos-ir neurons in the OVX-CT and sham-CT groups were significantly less than in the OVX-vehi and sham-vehi groups, respectively (p = 0.0090, p = 0.0090). The number of Fos-ir neurons in the OVX-CT-pcpa-group was significantly more than that of the OVX-CT-group (p = 0.0283), which means pcpa inhibits calcitonin induced reduction of c-Fos production.


CONCLUSIONS
The results in this study demonstrated that 1) the increase of c-Fos might be related to hyperalgesia in OVX-rats. 2) Calcitonin has an antinociceptive effect in both OVX and sham rats. 3) The central serotonergic system is involved in the antinociceptive properties of calcitonin.
Takayama
Bunji
B
Department of Orthopedic Surgery, Fukushima Medical University School of Medicine, 1-Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan. bun@fmu.ac.jp
Kikuchi
Shin-ichi
S
Konno
Shin-ichi
S
Sekiguchi
Miho
M
D000700:Analgesics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002116:Calcitonin / Q000378:metabolism / Q000494:pharmacology*; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D010024:Osteoporosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D010052:Ovariectomy; D010146:Pain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology
D000700:Analgesics; D015415:Biomarkers; D016760:Proto-Oncogene Proteins c-fos; D012702:Serotonin Antagonists; D012701:Serotonin; D002116:Calcitonin; D010134:Fenclonine