Limits...
An immunohistochemical study of the antinociceptive effect of calcitonin in ovariectomized rats.

Takayama B, Kikuchi S, Konno S, Sekiguchi M - BMC Musculoskelet Disord (2008)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Orthopedic Surgery, Fukushima Medical University School of Medicine, 1-Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan. bun@fmu.ac.jp

ABSTRACT

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.

Conclusion: 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.

Show MeSH

Related in: MedlinePlus

Expression in laminae I–II: Sham-calcitonin group vs sham-vehicle group. There were significantly fewer c-Fos immunoreactive neurons in the sham-calcitonin group than in the sham-vehicle group (p = 0.0090).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2654564&req=5

Figure 5: Expression in laminae I–II: Sham-calcitonin group vs sham-vehicle group. There were significantly fewer c-Fos immunoreactive neurons in the sham-calcitonin group than in the sham-vehicle group (p = 0.0090).

Mentions: Figure 2 shows illustrative cases of c-Fos immunoreactive neurons in each of the groups. The number of c-Fos immunoreactive neurons in the OVX-vehicle group was significantly greater than in the sham-vehicle group (p = 0.0367; Figure 3), indicating that OVX in rats result in a greater number of neurons in dorsal horn of the spinal cord that produce c-Fos after formalin test. There were significantly fewer c-Fos immunoreactive neurons in the OVX-calcitonin group than in the OVX-vehicle group (p = 0.0090; Figure 4), and significantly fewer c-Fos immunoreactive neurons in the sham-calcitonin group than in the sham-vehicle group (p = 0.0090; Figure 5). These findings mean that repeated calcitonin injection of both the OVX rats and the sham-operated rats result in fewer neurons in the dorsal horn of spinal cord that produced c-Fos after the formalin test. There were significantly more c-Fos immunoreactive neurons in the OVX-calcitonin-PCPA group than in the OVX-calcitonin group (p = 0.0283; Figure 6), but the difference from the OVX-vehicle group was not significant (Figure 6), indicating that the effect of repeated doses of calcitonin that decreases the number of c-Fos-producing neurons after the formalin test was abolished when the serotonin synthesis inhibitor was administered.


An immunohistochemical study of the antinociceptive effect of calcitonin in ovariectomized rats.

Takayama B, Kikuchi S, Konno S, Sekiguchi M - BMC Musculoskelet Disord (2008)

Expression in laminae I–II: Sham-calcitonin group vs sham-vehicle group. There were significantly fewer c-Fos immunoreactive neurons in the sham-calcitonin group than in the sham-vehicle group (p = 0.0090).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2654564&req=5

Figure 5: Expression in laminae I–II: Sham-calcitonin group vs sham-vehicle group. There were significantly fewer c-Fos immunoreactive neurons in the sham-calcitonin group than in the sham-vehicle group (p = 0.0090).
Mentions: Figure 2 shows illustrative cases of c-Fos immunoreactive neurons in each of the groups. The number of c-Fos immunoreactive neurons in the OVX-vehicle group was significantly greater than in the sham-vehicle group (p = 0.0367; Figure 3), indicating that OVX in rats result in a greater number of neurons in dorsal horn of the spinal cord that produce c-Fos after formalin test. There were significantly fewer c-Fos immunoreactive neurons in the OVX-calcitonin group than in the OVX-vehicle group (p = 0.0090; Figure 4), and significantly fewer c-Fos immunoreactive neurons in the sham-calcitonin group than in the sham-vehicle group (p = 0.0090; Figure 5). These findings mean that repeated calcitonin injection of both the OVX rats and the sham-operated rats result in fewer neurons in the dorsal horn of spinal cord that produced c-Fos after the formalin test. There were significantly more c-Fos immunoreactive neurons in the OVX-calcitonin-PCPA group than in the OVX-calcitonin group (p = 0.0283; Figure 6), but the difference from the OVX-vehicle group was not significant (Figure 6), indicating that the effect of repeated doses of calcitonin that decreases the number of c-Fos-producing neurons after the formalin test was abolished when the serotonin synthesis inhibitor was administered.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Orthopedic Surgery, Fukushima Medical University School of Medicine, 1-Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan. bun@fmu.ac.jp

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus