The aim of the present work was to study the involvement of glucocorticoid receptors and corticotropinreleasing 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.
Similar content being viewed by others
References
A. I. Bogdanov and N. I. Yarushkina, “Mechanisms of the effects of adrenocorticotropic hormone on pains sensitivity in rats,” Ros. Fiziol. Zh. im. I. M. Sechenova, 88, No. 5, 596–601 (2002).
A. I. Bogdanov and N. I. Yarushkina, “The role of hormones of the hypothalamo-hypophyseal-adrenocortical system in the analgesic effect of corticotropin-releasing hormone,” Ros. Fiziol. Zh. im. I. M. Sechenova, 92, No. 2, 262–270 (2006).
N. I. Yarushkina and A. I. Bogdanov, “The role of corticosterone in mediating the analgesic effect evoked by stimulation of central gray matter of the midbrain,” Fiziol. Zh. im. I. M. Sechenova, 84, No. 7, 642–650 (1998).
N. I. Yarushkina, A. I. Bogdanov, and A. A. Filaretov, “The central gray matter of the midbrain: role of corticosteroids in the analgesic effect,” Fiziol. Zh. im. I. M. Sechenova, 77, No. 4, 83–89 (1991).
V. P. Bakshi, S. Smith-Rode, S. M. Newman, D. E. Grigoriadis, and N. H. Kalin, “Reduction of stress-induced behavior by antagonism of corticotropin-releasing hormone 2 (CRH2) receptors in lateral septum or CRH1 receptors in amygdala,” J. Neurosci., 22, No. 7, 2926–2935 (2002)
T. L. Bale and W. W. Vale, “CRF and CRF receptors: Role in stress responsivity and other behaviors,” Ann. Rev. Pharmacol. Toxicol., 44, 525–557 (2004).
L. P. Filaretova, T. R. Bagaeva, and G. B. Makara, “Aggravation of nonsteroidal anti-inflammatory drug gastropathy by glucocorticoid deficiency or blockade of glucocorticoid receptor in rats,” Life Sci., 71, No. 21 2457–2468 (2002).
R. L. Hauger, V. Risbrough, O. Brauns, and F. M. Dautzenberg, “Corticotropin releasing factor (CRF) receptor signaling in the central nervous system: new molecular targets,” CNS Neurol. Disord. Drug Targets, 5, No. 4, 453–479 (2006).
D. L. Healy, G. P. Chrousos, N. M. Schulte, P. W. Gold, and G. D. Hodgen, “Increased adrenocorticotropin, cortisol, and arginine vasopressin secretion in primates after the antiglucocorticoid steroid RU 486: dose response relationships,” J. Clin. Endocrinol. Metab., 60, No. 1, 1–4 (1985).
M. Ising, U. S. Zimmermann, H. E. Kunzel, M. Uhr, A. C. Foster, S. M. Learned-Coughlin, F. Holsboer, and D. E. Grigoriadis, “Highaffinity CRF1 receptor antagonist NBI-34041: preclinical and clinical data suggest safely and efficacy in attenuating elevated stress response,” Neuropsychopharmacology, 32, No. 9, 1941–1949 (2007).
M. Larauche, S. Bradesi, M. Million, P. McLean, Y. Taché, E. A. Mayer, and J. A. McRoberts, “Corticotropin-releasing factor type 1 receptors mediate the visceral hyperalgesia induced by repealed psychological stress in rats,” Amer. J. Physiol., 294, No. 4, G1033–G1040 (2008).
W. R. Lariviere and R. Melzack, “The role of corticotropin-releasing factor in pain and analgesia,” Pain, 84, No. 1, 1–12 (2000).
R. Likar, S. A. Mousa, H. Steinkellner, W. Koppert, G. Philippitsch, C. Stein, and M. Schäfer, “Involvement of intra-articular corticotropin-releasing hormone in postoperative pain modulation,” Clin. J. Pain, 23, No. 2, 136–142 (2007).
J. Lukkes, G. Forster, K. J. Renner, and C. H. Summers, “Corticotropin-releasing factor 1 and 2 receptors in the dorsal raphe differentially affect serotonin release in the nucleus accumbens,” Eur. J. Pharmacol., 578, No. 2–3, 185–193 (2008).
V. Martinez, L. Wang, J. Rivier, D. Grigoriadis, and Y. Taché, “Central CRF, urocortins and stress increase colonic transit via CRF1 receptors while activation of CRF2 receptors delays gastric transit in mice,” J. Physiol., 556, No. 1, 221–234 (2004).
M. Million, C. Maillot, P. Saunders, J. Rivier,W. Vale, and T. Taché, “Human urocortin II, a new CRF-related peptide, displays selective CRF(2)-mediated action on gastric transit in rats,” Amer. J. Physiol., 282, No. 1, G34–G40 (2002).
M. Million, L. Wang, Y. Wang, D. W. Adelson, P. Q. Yuan, C. Maillot, S. V. Coutinho, J. A. McRoberts, A. Bayati, H. Mattsson, V. Wu, J. Y. Wei, J. Rivier, W. Vale, E. A. Mayer, and T. Taché, “CRF2 receptor activation prevents colorectal distension induced visceral pain and spinal ERK1/2 phosphorylation in rats,” Gut, 55, No. 2, 172–181 (2006).
S. A. Mousa, C. P. Bopaiah, C. Stein, and M. Schafer, “Involvement of corticotropin-releasing hormone receptor subtypes 1 and 2 in peripheral opioid-mediated inhibition of inflammatory pain,” Pain, 106, No. 3, 297–307 (2003).
M. Nijsen, N. Ongenae, A. Meulemans, and B. Coulie, “Divergent role for CRF1 and CRF2 receptors in the modulation of visceral pain,” Neurogastroenterol. Motil., 17, No. 3, 423–432 (2005).
C. L. Ribier, D. E. Grigoriadis, and J. E. Rivier, “Role of corticotropin-releasing factor receptors type 1 and 2 in modulating the rat adrenocorticotropin response to stressors,” Endocrinology, 144, No. 6, 2396–2403 (2003).
C. Todorovic, J. Radulovic, O. Jahn, M. Radulovic, T. Sherrin, C. Hippel, and J. Spiess, “Differential activation of CRF receptor subtypes removes stress-induced memory deficit and anxiety,” Eur. J. Neurosci., 25, No. 11, 3385–3397 (2007).
Q. Wang, L. Mao, and J. Han, “Analgesia from electrical stimulation of the hypothalamic arcuate nucleus in pentobarbital-anesthetized rats,” Brain Res., 526, No. 2, 221–227 (1990).
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 94, No. 10, pp. 1118–1125, October, 2008.
Rights and permissions
About this article
Cite this article
Yarushkina, N.I., Bagaeva, T.R. & Filaretova, L.P. Analgesic Actions of Corticotropin-Releasing Factor (CRF) on Somatic Pain Sensitivity: Involvement of Glucocorticoid and CRF-2 Receptors. Neurosci Behav Physi 39, 819–823 (2009). https://doi.org/10.1007/s11055-009-9212-9
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11055-009-9212-9