Laboratory of Experimental Endocrinology, Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia.
J Physiol Pharmacol. 2011 Oct;62(5):541-8.
Corticotropin-releasing factor (CRF) is an important regulator of physiological functions and behavior in stress. Analgesia is one of the characteristics of stress reaction and CRF is involved in providing stress-induced analgesia, however, the underlying mechanisms remain to be determined. Exogenous CRF mimics stress effects on pain sensitivity and causes analgesic effect. The present study was performed to investigate the participation of endogenous glucocorticoids in analgesic effects induced by central administration of CRF in anesthetized rats. The participation of glucocorticoids was studied by pharmacological suppression of the hypothalamic-pituitary-adrenocortical (HPA) axis as well as an occupation of glucocorticoid receptors by its antagonist RU 38486. Since CRF administration causes the release of β-endorphin from the pituitary, the opioid antagonist naltrexone was used to determine the contribution of opioid-dependent mechanism to CRF-induced analgesia. An electrical current threshold test was applied for measurement of somatic pain sensitivity in anesthetized rats. Intracerebroventricular administration of CRF (2 μg/rat) caused analgesic effects (an increase of pain thresholds) and an increase in plasma corticosterone levels. Pretreatment with naltrexone did not change analgesic effects of central CRF as well as corticosterone levels in blood plasma. However, pharmacological suppression of the HPA axis leading to an inability of corticosterone release in response to CRF resulted in an elimination of CRF-induced analgesic effects. Pretreatment with RU 38486 also resulted in an elimination of CRF-induced effects. The data suggest that CRF-induced analgesic effects may be mediated by nonopioid mechanism associated with endogenous glucocorticoids released in response to central CRF administration.
促肾上腺皮质释放因子（CRF）是应激生理功能和行为的重要调节因子。镇痛是应激反应的特征之一，CRF 参与提供应激诱导的镇痛，但潜在机制仍需确定。外源性 CRF 模拟应激对疼痛敏感性的影响，并产生镇痛作用。本研究旨在探讨内源性糖皮质激素在麻醉大鼠中枢给予 CRF 诱导的镇痛效应中的作用。通过药理学抑制下丘脑-垂体-肾上腺皮质轴（HPA）以及糖皮质激素受体拮抗剂 RU 38486 的占据来研究糖皮质激素的参与。由于 CRF 给药会引起垂体释放 β-内啡肽，因此使用阿片受体拮抗剂纳曲酮来确定阿片依赖机制对 CRF 诱导的镇痛的贡献。应用电流阈值测试测量麻醉大鼠的躯体痛觉敏感性。脑室内给予 CRF（2μg/大鼠）引起镇痛作用（疼痛阈值增加）和血浆皮质酮水平升高。纳曲酮预处理不会改变中枢 CRF 的镇痛作用以及血液中的皮质酮水平。然而，HPA 轴的药理学抑制导致皮质酮释放对 CRF 反应的丧失，导致 CRF 诱导的镇痛作用消除。RU 38486 的预处理也导致 CRF 诱导的作用消除。数据表明，CRF 诱导的镇痛作用可能通过与内源性糖皮质激素释放相关的非阿片机制介导，该机制对中枢 CRF 给药有反应。
