The aim of the present work was to study the involvement of glucocorticoid receptors and corticotropin-releasing factor type 2 receptors (CRF-2 receptors) in mediating the analgesic effects of CRF on somatic pain sensitivity. The involvement of glucocorticoid and CRF-2 receptors in the development of analgesia evoked by systemic administration of CRF was studied by blockade of these receptors by their specific antagonists RU 38486 and astressin 2-B, respectively, in anesthetized rats. Pain sensitivity was tested before and 30 min after administration of CRF in terms of the threshold of the pain reaction induced by stimulation of the rat's tail with an electric current. Blockade of glucocorticoid receptors induced partial suppression of the analgesic action of CRF, while blockade of CRF-2 receptors produced complete suppression of the analgesic effect. These results provide evidence that glucocorticoid and CRF-2 receptors are involved in mediating the analgesic effects of CRF.
Experimental studies on the effects of stress on blood corticosteroid levels and the appearance of analgesia were carried out on rats anesthetized with Nembutai (4 mg/100 g). Stress, consisting of stimulation of the hind footpad with a current at 0.7 mA, produced parallel changes in plasma corticosteroid concentrations and the threshold of a pain response. Functional blockade of the hypophyseal-adrenocortical system, produced by systemic administration of hydrocortisone (15 mg/100 g) or by implantation of dexamethasone (200 micrograms) above the paraventricular nucleus of the hypothalamus, resulted in reductions in stress-induced analgesia. Dosage with naloxone (1 and 10 mg/kg) had no effect on the level of analgesia or corticosteroid concentrations. It is concluded that stress-induced analgesia not mediated by opioids is corticosteroid-dependent.
The present review addresses analysis of data demonstrating the role of the hypothalamo-hypophyseal-adrenocortical axis (HHACA) in controlling pain sensitivity. Experiments on rats have demonstrated the analgesic effects of exogenous hormones of all components of the HHACA - corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and glucocorticoids - in the same models, and have also shown that the opioid and non-opioid mechanisms contribute to the development of the analgesia induced by these hormones. Endogenous glucocorticoids are involved in the development of analgesia mediated by non-opioid mechanisms. Along with the non-opioid mechanisms associated with endogenous glucocorticoids, the analgesic effect of ACTH can be mediated by the opioid mechanism. Unlike the situation with ACTH, the analgesic effect of CRH is mediated exclusively by non-opioid mechanisms, one of which is associated with HHACA hormones, while the other, appearing only on systemic administration, is not associated with these hormones. The actions of glucocorticoids on pain are mediated by neurons in the central gray matter of the midbrain.
Experiments on conscious male Sprague-Dawley rats were performed to study the effects of adrenocorticotropic hormone (ACTH) on pain reactions. Pain sensitivity was assessed in terms of the latent period of tail withdrawal in response to heat. Systemic administration of ACTH and glucocorticoids to animals with normal levels of hormone production led to increases in the latent period of the tailflick reaction. The roles of glucocorticoids and opioid peptides in ACTH-induced analgesia were addressed in experiment on animals with deficient glucocorticoid production and animals in which opiate receptors were blocked with naltrexone. Deficiency in glucocorticoid production had no effect on ACTH-induced increases in the latent period of the tailflick reaction, while blockade of opiate receptors completely eliminated this effect of ACTH. ACTH-induced analgesia in conscious rats is mediated by opiate receptors and not by glucocorticoids.
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