Mandeville, Bernard

Peer reviewe

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

<p>Abstract</p> <p>Background</p> <p>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. Ovariectomaized (OVX) rats exhibit the same hormonal changes as observed in humans with osteoporosis and are an animal model of postmenopousal osteoporosis. The aim of this study to investigate antinociceptive effect of calcitonin in OVX rats using the immunohistochemical study.</p> <p>Methods</p> <p>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 recieved 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 calcitonon 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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

Behavioural and cardiovascular effects of orexin-A infused into the central amygdala under basal and fear conditions in rats

The neuropeptide orexin-A (OX-A) has diverse functions, including maintaining arousal, autonomic control, motor activity and stress responses. These functions are regulated at different terminal regions where OX-A is released. The current study examined the physiological and behavioural effects of OX-A microinjections into the central amygdala (CeA) under basal and stressed conditions in rats. When OX-A was microinjected into the CeA and the animals returned to the home-cage, heart rate and mean arterial pressure were increased compared to vehicle-injected controls. General activity of the animal was also increased, indicating that OX-A activity in CeA contributes to increased arousal. This outcome is similar to the effects of central intracerebroventricular infusions of OX-A, as well as the cardiovascular effects previously demonstrated at many of OX's efferent hypothalamic and brainstem structures. In a second study, animals were fear-conditioned to a context by delivery of electric footshocks and then animals were re-exposed to the conditioned context at test. When OX-A was microinjected at test, freezing behaviour was reduced and there was a corresponding increase in the animal's activity but no impact on the pressor and cardiac responses (i.e, blood pressure and heart rate were unchanged). This reduction in freezing suggests that OX-A activates amygdala neurons that inhibit freezing, which is similar to the actions of other neuropeptides in the CeA that modulate the appropriate defence response to fearful stimuli. Overall, these data indicate that the CeA is an important site of OX-A modulation of cardiovascular and motor activity, as well as conditioned freezing responses