Pain is a salient "stressor" that is mediated by corticotropin-releasing factor-1 receptors.

Abstract

Corticotropin-releasing factor (CRF) plays a major role in controlling the body's response to stress. Because painful conditions are inherently stressful, we hypothesize that CRF may act via CRF-1 receptors to contribute to the pain experience. Studies were designed to investigate whether blocking CRF-1 receptors with selective antagonists or reducing their expression with CRF-Saporin, would attenuate ulcer, inflammatory- and neuropathic-like pain. Five experimental designs were undertaken. In experiment 1, ulcer pain was induced in mice following oral administration of indomethacin, while in experiments 2 and 3, inflammatory pain was induced in rats with either carrageenan or FCA, respectively. For these studies, animals were dosed with CP-154,526 (3, 10, 30 mg/kg) and NBI 27914 (1-30 mg/kg) 1 h prior to the assessment of tactile, thermal or mechanical hypersensitivity, respectively. In experiment 4, neuropathic pain was induced. Twenty-one days following spinal nerve ligation (SNL), animals received CRF-Saporin or control. Three weeks later tactile allodynia was assessed. Similarly, in experiment 5, a separate set of rats received CRF-Saporin or control. Twenty-one days later, mechanical hyperalgesia was assessed following intraplantar carrageenan. Results from the antagonist studies showed that CP-154,526 and NBI 27914 either fully or partially reversed the referred ulcer pain with minimal effective doses (MED) equal to 3 and 10 mg/kg, respectively. Similarly, both NBI 27914 and CP-154,526 reversed the thermal and mechanical hypersensitivity elicited by carrageenan and FCA with MEDs </= 5 and 10 mg/kg, respectively. Findings from the two CRF-Saporin studies determined that pre-treatment with this toxin significantly attenuated SNL- and carrageenan-induced tactile hypersensitivity. Together, these findings suggest that CRF-1 receptors mediate pain and implicate CRF in this regard.

• Authors: Michele Hummel, Terri Cummons, Peimin Lu, Lilly Mark, James E Harrison, Jeffrey D Kennedy, Garth T Whiteside
• Journal: Neuropharmacology (Neuropharmacology) Vol. 59 Issue 3 Pg. 160-6 (Sep 2010) ISSN: 1873-7064 [Electronic] England
• PMID: 20470804 (Publication Type: Journal Article)
• Copyright: Copyright 2010 Elsevier Ltd. All rights reserved.

Chemical References

• 2-methyl-4-(N-propyl-N-cycloproanemethylamino)-5-chloro-6-(2,4,6-trichloranilino)pyrimidine
• Aniline Compounds
• Anti-Inflammatory Agents, Non-Steroidal
• CP 154526
• Pyrimidines
• Pyrroles
• Receptors, Corticotropin-Releasing Hormone
• Carrageenan
• Corticotropin-Releasing Hormone
• Indomethacin

Topics

• Aniline Compounds (pharmacology, therapeutic use)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Carrageenan
• Corticotropin-Releasing Hormone (pharmacology, therapeutic use)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Interactions
• Hyperalgesia (drug therapy)
• Indomethacin (pharmacology, therapeutic use)
• Inflammation (chemically induced, complications)
• Male
• Mice
• Pain (complications, drug therapy, etiology)
• Pain Threshold (drug effects)
• Pyrimidines (pharmacology, therapeutic use)
• Pyrroles (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Receptors, Corticotropin-Releasing Hormone (antagonists & inhibitors, metabolism)
• Spinal Cord Injuries (complications)
• Stomach Ulcer (complications, drug therapy)
• Stress, Psychological (drug therapy, etiology, metabolism)