Differential effects of CRF1 and CRF2 receptor antagonists on pain-related sensitization of neurons in the central nucleus of the amygdala.

Abstract

As a hormone in the hypothalamic-pituitary-adrenocortical (HPA) axis corticotropin-releasing factor (CRF) mediates stress responses. CRF can also act as a neuromodulator of synaptic transmission outside the HPA axis. A major site of extrahypothalamic expression of CRF and its G-protein-coupled receptors is the amygdala, a key player in affect-related disorders such as anxiety. The laterocapsular division of the central nucleus of the amygdala (CeLC) is important for the modulation of pain affect. This study determined the effects of CRF1 and CRF2 receptor antagonists in CeLC neurons in an arthritis pain model. Extracellular single-unit recordings were made from CeLC neurons in anesthetized adult rats. All neurons responded more strongly to noxious than to innocuous mechanical stimulation (compression) of peripheral tissues, including the knee. Evoked responses and background activity were measured before and during the development of a kaolin/carrageenan-induced knee joint arthritis. Drugs were administered into the CeLC by microdialysis before and/or after arthritis induction. All CeLC neurons showed increased responses to mechanical stimuli ("sensitization") 5-6 h postinduction of arthritis. A selective CRF1 receptor antagonist (NBI27914; 1-100 microM, concentration in microdialysis probe; 15 min) inhibited evoked responses and background activity in arthritis (n = 9) but had no effect under normal conditions before arthritis (n = 9). In contrast, a selective CRF2 receptor antagonist (Astressin-2B; 1-100 microM, 15 min) had no effect in arthritis (n = 7) but increased the neurons' responses under normal conditions (n = 8). These data suggest that CRF1 receptors in the amygdala contribute to pain-related sensitization, whereas the normally inhibitory function of CRF2 receptors is lost in the arthritis pain model.

• Authors: Guangchen Ji, Volker Neugebauer
• Journal: Journal of neurophysiology (J Neurophysiol) Vol. 97 Issue 6 Pg. 3893-904 (Jun 2007) ISSN: 0022-3077 [Print] United States
• PMID: 17392412 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• 2-methyl-4-(N-propyl-N-cycloproanemethylamino)-5-chloro-6-(2,4,6-trichloranilino)pyrimidine
• Aniline Compounds
• CRF receptor type 2
• Peptide Fragments
• Pyrimidines
• Receptors, Corticotropin-Releasing Hormone
• astressin B
• CRF receptor type 1
• Corticotropin-Releasing Hormone

Topics

• Action Potentials (drug effects)
• Amygdala (pathology)
• Aniline Compounds (pharmacology)
• Animals
• Arthritis (chemically induced, complications)
• Corticotropin-Releasing Hormone (pharmacology)
• Dose-Response Relationship, Drug
• Drug Interactions
• Male
• Neural Inhibition (drug effects, physiology)
• Neurons (drug effects, physiology)
• Pain (etiology, pathology)
• Pain Measurement (methods)
• Pain Threshold (drug effects)
• Peptide Fragments (pharmacology)
• Physical Stimulation (methods)
• Pyrimidines (pharmacology)
• Rats
• Receptors, Corticotropin-Releasing Hormone (antagonists & inhibitors)
• Time Factors