Skip to main content
Log in

Effects of Corticotropin-Releasing Factor (CRF) on Somatic Pain Sensitivity in Conscious Rats: Involvement of Types 1 and 2 CRF Receptors

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

Corticotrophin-releasing factor (CRF) is involved in regulating pain sensitivity and can elicit analgesic effects in animals and humans. The aim of the present work was to investigate the involvement of types 1 and 2 CRF receptors (CRF-1 and CRF-2 receptors) in mediating the analgesic action of CRF on somatic pain sensitivity when given systemically to conscious rats. Somatic pain sensitivity was tested in terms of the latent period (LP) of the tailflick reaction in response to thermal stimulation (the tail flick test). The involvement of CRF-1 and CFR-2 receptors was studied by systemic administration of their specific antagonists NBI 27914 and astressin 2B, respectively. Systemic administration of CRF increased the latent period of the pain reaction (it had an analgesic effect). Prior administration of NBI 27914 or astressin 2B eliminated the analgesic effect of CRF. In addition, administration of NBI 27914 affected the basal latent period of the pain reaction, increasing it. These data provide evidence that the analgesic effect of CRF may be mediated by both CRF-1 and CRF-2 receptors. CRF-1 receptors, unlike CRF-2 receptors, may also be involved in regulating the basal level of pain sensitivity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. N. I. Yarushkina and T. R. Bagaeva, “Mechanisms of the analgesic effect of corticotropin-releasing factor in conscious rats,” Ros. Fiziol. Zh., 96, No. 2, 128–137 (2010).

    CAS  Google Scholar 

  2. N. I. Yarushkina, T. R. Bagaeva, and L. P. Filaretova, “The analgesic effect of corticotropin-releasing factor (CRF) on somatic pain sensitivity: the involvement of glucocorticoids and CRF-2 receptors,” Ros. Fiziol. Zh., 94, No. 10, 1118–1125 (2008).

    CAS  Google Scholar 

  3. N. I. Yarushkina, T. R. Bagaeva, and L. P. Filaretova,, “Mechanisms of the analgesic action of corticotropin-releasing factor on pain sensitivity in rats,” Ros. Fiziol. Zh., 99, No. 7, 806–819 (2013).

    Google Scholar 

  4. R. E. Abdelhamid, K. J. Kovacs, J. D. Pasley, et al., “Forced swim-induced musculoskeletal hyperalgesia is mediated by CRF2 receptors but not by TRPV 1 receptors,” Neuropharmacology, 72, 29–37 (2013).

    Article  CAS  PubMed  Google Scholar 

  5. F. J. Ayesta and K. E. Nikolarakis, “Peripheral but not intracerebroventricular corticotropin-releasing hormone (CRH) produces antinociception which is not opioid mediated,” Brain Res., 503, No. 2, 219–224 (1989).

    Article  CAS  PubMed  Google Scholar 

  6. M. S. Cepeda, I. Bonney, J. Moyano, and D. B. Carr, “Corticotropin releasing hormone (CRH) produces analgesia in a thermal injury model independent of its effect on systemic beta-endorphin and corticosterone,” Regul. Pept., 118, No. 1–2, 39–43 (2004).

    Article  CAS  PubMed  Google Scholar 

  7. M. Dolatshahi-Somehsofla, S. Esmaeili-Mahani, F. Motamedi, et al., “Adrenalectomy potentiates the antinociceptive effects of calcium channel blockers,” Pharm. Biochem. Behav., 92, No. 2, 327–334 (2009).

    Article  CAS  Google Scholar 

  8. Y. Fu and V. Neugebauer, “Differential mechanisms of CRF1 and CRF2 receptor functions in the amygdala in pain-related synaptic facilitation and behavior,” J. Neurosci., 28, No. 15, 3861–3876 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. K. M. Hargreaves, C. D. Flores, and G. Mueller, “The role of pituitary β-endorphin in mediating CRF-induced antinociception,” Am. J. Physiol., 258, No. 1, E235–E242 (1990).

    CAS  PubMed  Google Scholar 

  10. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. M. Hummel, T. Cummons, P. Lu, et al., “Pain is salient ‘stressor’ that is mediated by corticotrophin-releasing factor-1 receptors,” Neurophar macology, 59, 160–166 (2010).

    Article  CAS  Google Scholar 

  12. G. Ji and V. Negebauer, “Pro- and antinociceptive effects of corticotropin-releasing factor (CRF) in central amygdala neurons are mediated through different receptors,” J. Neurophysiol., 99, No. 3, 1201–1212 (2008).

    Article  CAS  PubMed  Google Scholar 

  13. G. Ji, Y. Fu, H. Adwanikar, and V. Negebauer, “Non-pain-related CRF1 activation in the amygdala facilitates synaptic transmission and pain responses,” Mol. Pain, 9, 2. DOI: 10.1186/1744-8069-9-2 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. G. Ji, Y. Fu, K. A. Ruppert, and V. Negebauer, “Pain-related anxiety-like behavior requires CRF1 receptors in the amygdala,” Mol. Pain, 3, 13, DOI: 10.1186/1744-8069-433-13 (2013).

    Article  Google Scholar 

  15. W. R. Lariviere and R. Melzack, “The role of corticotropin-releasing factor in pain and analgesia,” Pain, 84, No. 1, 1–12 (2000).

    Article  CAS  PubMed  Google Scholar 

  16. W. R. Lariviere, P. Fiorenzani, I. Ceccarelli, et al., “Central CRH administration changes formalin pain responses in male and female rats,” Brain Res., 1383, 128–134 (2011).

    Article  CAS  PubMed  Google Scholar 

  17. D Le Bars, M. Gozariu, and S. W. Cadden, “Animal models of nociception,” Pharmacol. Rev., 53, No. 4, 597–652 (2001).

    PubMed  Google Scholar 

  18. R. Likar, S. A. Mousa, H. Steinkellner, et al., “Involvement of intra-articular corticotropin-releasing hormone in postoperative pain modulation,” Clin. J. Pain, 23, No. 2, 136–142 (2007).

    Article  PubMed  Google Scholar 

  19. V. Martinez, L. Wang, J. Rivier, et al., “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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. R. Matejec, H. Uhlick, C. Hotz, et al., “Corticotropin-releasing hormone reduces pressure pain sensitivity in humans without involvement of beta-endorphin (1-31), but does not reduce heat pain sensitivity,” Neuroendocrinology, 82, No. 3–4, 185–197 (2005).

    Article  CAS  PubMed  Google Scholar 

  21. T. Miguel and R. Nunes-de-Souza, “Anxiogenic and antinociceptive effects of corticotrophin-releasing factor (CRF) injections into periaqueductal gray are modulated by CRF1 receptor in mice,” Horm. Behav., 60, No. 3, 292–300 (2011).

    Article  CAS  PubMed  Google Scholar 

  22. 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).

    Article  CAS  PubMed  Google Scholar 

  23. S. A. Mousa, C. P. Bopaiah, J. F. Richter, et al., “Inhibition of inflammatory pain by CRF at peripheral, spinal and supraspinal sites: involvement of areas coexpressing CRF receptors and opioid peptides,” Neuropsychopharmacology, 32, No. 12, 2530–2542 (2007).

    Article  CAS  PubMed  Google Scholar 

  24. M. Nijsen, N. Ongenae, A. Meulemans, and B. Coulie, “Divergent role for CRF 1 and CRF2 receptors in the modulation of visceral pain,” Neurogastroenterol. Motil., 17, No. 3, 423–432 (2005).

    Article  CAS  PubMed  Google Scholar 

  25. T. Nozu and M. Kudaira, “Corticotropin-releasing factor induces rectal hypersensitivity after repetitive painful rectal distention in healthy humans,” J. Gastroenterol., 41, 740–744 (2006).

    Article  CAS  PubMed  Google Scholar 

  26. C. L. Rivier, 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).

    Article  CAS  PubMed  Google Scholar 

  27. D. Roosterman, T. George, S. W. Schneider, et al., “Neuronal control of skin function: the skin as a neuroimmunoendocrine organ,” Physiol. Rev., 86, No. 4, 1309–1379 (2006).

    Article  CAS  PubMed  Google Scholar 

  28. T. Rouwette, P. Vanelderen, E. W. Roubos, et al., “The amygdala, a relay station for switching on and off pain,” Eur. J. Pain, 16, 782–792 (2012).

    Article  CAS  PubMed  Google Scholar 

  29. S. Samuelsson, J. S. Lange, R. T. Hinkle, et al., “Corticotropin-releasing factor 2 receptor localization in skeletal muscle,” J. Histochem. Cytochem, 52, No. 7, 967–977 (2004).

    Article  CAS  PubMed  Google Scholar 

  30. Y. Tache, “Stress activates corticotropin releasing factor signaling pathways,” in: Chemistry and Molecular Aspects of Drug Design and Action, E. A. Rekka and P. N. Kouronakis (eds.), CRC Press (2008), pp. 75–90.

  31. J. P. Vit, D. J. Clauw, T. Moallem, et al., “Analgesia and hyperalgesia from CRF receptor modulation in the central nervous system of Fischer and Lewis rats,” Pain, 121, No. 3, 241–260 (2006).

    Article  CAS  PubMed  Google Scholar 

  32. N. I. Yarushkina, A. I. Bogdanov, and L. P. Filaretova, “Somatic pain sensitivity during formation and healing of acetic acid-induced gastric ulcers in conscious rats,” Auton. Neurosci. Basic Clin., 126-127, No. 1–2, 100–105 (2006).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to N. I. Yarushkina.

Additional information

Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 100, No. 11, pp. 1287–1296, November, 2014.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yarushkina, N.I., Bagaeva, T.R. & Filaretova, L.P. Effects of Corticotropin-Releasing Factor (CRF) on Somatic Pain Sensitivity in Conscious Rats: Involvement of Types 1 and 2 CRF Receptors. Neurosci Behav Physi 46, 472–477 (2016). https://doi.org/10.1007/s11055-016-0260-7

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-016-0260-7

Keywords

Navigation