J Korean Med Sci.  2010 Nov;25(11):1646-1651. 10.3346/jkms.2010.25.11.1646.

The Expression of Corticotropin-Releasing Factor in the Central Nucleus of the Amygdala, Induced by Colorectal Distension, is Attenuated by General Anesthesia

• Kim SH
• Han JE
• Hwang S
• Oh DH

• KMID: 1779236
• DOI: http://doi.org/10.3346/jkms.2010.25.11.1646

Abstract

Corticotrophin-releasing factor (CRF), a key regulator of the hypothalamic-pituitary axis, is expressed in the central nucleus of the amygdala (CeA) and its expression is upregulated in stress-related disorders. We investigated here the effect of noxious colorectal distension (CRD) on the expression of CRF in the CeA of conscious and unconscious rats. Adult male rats with or without general anesthesia were exposed to visceral pain induced by CRD for 5 min; this procedure was repeated 3 times with 1 min resting after each distension. The rats were sacrificed and sections of the CeA were immunostained for CRF as an indicator for anxiety response, and for phosphorylated extracellular signal-regulated kinase (p-ERK) as a marker for pain-specific activation of neurons; sections of lumbosacral spinal cord were immunostained for c-Fos as a marker for activation of spinal neurons. CRD elicited a significant increase in the expression of CRF and p-ERK in the CeA and of c-Fos in the spinal cord. General anesthesia attenuated the increase in CRF and p-ERK in the CeA, but did not affect the expression of spinal c-Fos. These results suggest that conscious recognition of pain at higher brain centers is an important determinant of CRF expression in the CeA.

Keyword

Corticotropin-Releasing Hormone; Amygdala; Pain; Mental Disorders

MeSH Terms

Amygdala/*metabolism/pathology
*Anesthesia, General
Animals
Colon
Corticotropin-Releasing Hormone/*metabolism
Extracellular Signal-Regulated MAP Kinases/metabolism
Immunohistochemistry
Male
Neurons/metabolism
Pain/prevention & control
Phosphorylation
Proto-Oncogene Proteins c-fos/metabolism
Rats
Rats, Sprague-Dawley
Rectum

Figure

• 

  Fig. 1 Immunostaining for CRF in the central nucleus of the amygdala (CeA) in rats of the control group (A, CON), the colorectal distension group (B, CRD), and the CRD under general anesthesia group (C, Anesthesia+CRD). The immunostaining for CRF was higher in rats with CRD than in controls three days (72 hr) after CRD. However, the CRF-positive area in rats with CRD under general anesthesia was significantly lower than that of conscious animals (D, area [mean±SEM] in the 5 brain sections 400 µm apart, *P<0.005 vs CON, †P<0.005 vs CRD, one-way ANOVA). Scale bar: 200 µm.

• 

  Fig. 2 Immunostaining for phospho-ERK (pERK) in the central nucleus of the amygdala (CeA) in rats of the control group (A, CON), the colorectal distension group (B, CRD), and the CRD under general anesthesia group (C, Anesthesia+CRD). The number of pERK-positive neurons was higher in rats with CRD than in controls 30 min after CRD. The increase of pERK-positive neurons was significantly lower in rats with general anesthesia (D, number of neurons [mean±SEM] in the 5 brain sections 400 µm apart, *P<0.005 vs CON, †P<0.005 vs CRD, one-way ANOVA). Scale bar: A-C, 50 µm.

• 

  Fig. 3 Immunostaining for c-Fos in the spinal dorsal horn in rats of the control group (A, CON), the colorectal distension group (B, CRD), and the CRD under general anesthesia group (C, Anesthesia+CRD). 30 min after CRD, the number of c-Fos-positive nuclei was higher in rats with CRD than in controls. The difference in expression of c-Fos between conscious and anesthetized rats was not significant (D, number of nuclei [mean±SEM] in the 5 brain sections 300 µm apart, *P<0.05 vs CON, one-way ANOVA). Scale bar: A-C, 100 µm.

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