Analgesia and hyperalgesia from CRF receptor modulation in the central nervous system of Fischer and Lewis rats.

Abstract

This study examines the contribution of central corticotropin-releasing factor (CRF) to pain behavior. CRF is the principal modulator of the hypothalamo-pituitary-adrenal (HPA) axis, in addition to acting on many other areas of the central nervous system. We compared nociceptive thresholds (heat and mechanical) and pain behavior in response to a sustained stimulus (formalin test) between Fischer and Lewis rats that have different HPA axis activity. Intracerebroventricular (i.c.v.) administration of CRF produced dose-dependent antinociception at a lower dose in Lewis (40 ng, paw pinch 71+/-0 g) compared to Fischer rats (200 ng, 112+/-3 g). The antinociceptive effect of CRF was mostly preserved in adrenalectomized Fischer rats. The i.c.v. administration of the CRF receptor antagonist, astressin, had a hyperalgesic effect, suggesting that CRF is tonically active. Lewis rats required higher doses of astressin (5 ng, paw pinch 51+/-1 g) to show nociceptive effects compared to Fischer rats (1 ng, 79+/-1 g). Only Lewis rats vocalized during mechanical stimulus, and this behavior was prevented by diazepam or morphine but was worsened by CRF, despite its antinociceptive property. In the formalin test, CRF and astressin had the largest effect on the interphase suggesting that they act on the endogenous pain inhibitory system. CRF also increased anxiety/fear-like behaviors in the forced swim and predator odor tests. Our results establish that central CRF is a key modulator of pain behavior and indicates that CRF effects on nociception are largely independent of its mood modulating effect as well as its control of the HPA axis.

• Authors: Jean-Philippe Vit, Daniel J Clauw, Theodore Moallem, Abdenasser Boudah, Peter T Ohara, Luc Jasmin
• Journal: Pain (Pain) Vol. 121 Issue 3 Pg. 241-260 (Apr 2006) ISSN: 0304-3959 [Print] United States
• PMID: 16495007 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Analgesics
• Neuroprotective Agents
• Peptide Fragments
• Receptors, Corticotropin-Releasing Hormone
• astressin
• Corticotropin-Releasing Hormone

Topics

• Adrenalectomy
• Analgesics (metabolism, pharmacology)
• Animals
• Anxiety (chemically induced, metabolism)
• Corticotropin-Releasing Hormone (adverse effects, metabolism, pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Fear (drug effects, physiology)
• Female
• Hyperalgesia (metabolism, physiopathology)
• Hypothalamo-Hypophyseal System (drug effects, metabolism)
• Injections, Intraventricular
• Neuroprotective Agents (adverse effects)
• Pain (metabolism, physiopathology)
• Pain Measurement (drug effects)
• Peptide Fragments (adverse effects)
• Pituitary-Adrenal System (drug effects, metabolism)
• Rats
• Rats, Inbred F344
• Rats, Inbred Lew
• Receptors, Corticotropin-Releasing Hormone (antagonists & inhibitors, metabolism)
• Vocalization, Animal (drug effects, physiology)