title: Knockdown of steroid receptors in the central nucleus of the amygdala induces heightened pain behaviors in the rat.
abstract: Previously we demonstrated that exposure of the central nucleus of the amygdala (CeA) to elevated corticosterone (CORT) induces nociceptive behaviors that are reversed by glucocorticoid and/or mineralocorticoid (GR/MR) receptor antagonism. Here we test the hypothesis that in a cholesterol (CHOL)-implanted control rat, selective knockdown of GR/MR in the CeA would, via a corticotropin-releasing factor (CRF)-mediated mechanism, replicate the nociceptive behaviors produced by elevated amygdala CORT. Micropellets of CHOL or CORT were stereotaxically placed on the dorsal margin of the CeA. Cannulae were implanted into the CeA for the delivery of vehicle or oligodeoxynucleotide (ODN) of either antisense (ASO) or random sequences (RSO) targeting GR or MR. Visceromotor behavioral response quantified visceral sensitivity in response to colonic distension, while von Frey filaments assessed somatic sensitivity. Receptor expression was determined with qRT-PCR. In CHOL implanted controls, knockdown of GR in the CeA increased both colonic and somatic sensitivity, whereas selective knockdown of MR in the CeA induced colonic hypersensitivity without affecting somatic sensitivity. CRF expression in the CeA was increased in CHOL-implanted rats treated with GR or MR ASO and resembled the augmented CRF expression seen in the CORT-implanted rats. This is the first study to demonstrate that decreasing either GR or MR within the CeA is sufficient to induce visceral hypersensitivity whereas somatic hypersensitivity developed after only GR knockdown. The loss of either GR or MR was associated with an increased CRF expression, and may represent a common mechanism for the development of CeA-mediated nociceptive behaviors.
authors: Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors: Anthony C
authors: AC
authors: Johnson
authors: Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, USA; Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA; VA Medical Center, University of Oklahoma Health Science Center, Oklahoma City, OK, USA. Electronic address: Beverley-Greenwood@ouhsc.edu.
authors: Beverley
authors: B
authors: Greenwood-Van Meerveld
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D066274:Central Amygdaloid Nucleus / Q000187:drug effects / Q000502:physiology*; D002784:Cholesterol / Q000008:administration & dosage; D003345:Corticosterone / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008901:Mineralocorticoids / Q000378:metabolism; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage; D010146:Pain / Q000209:etiology*; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D011916:Rats, Inbred F344; D011965:Receptors, Glucocorticoid / Q000172:deficiency* / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000172:deficiency / Q000235:genetics; D059265:Visceral Pain / Q000209:etiology
chemical_list: D008901:Mineralocorticoids; D020319:Oligodeoxyribonucleotides, Antisense; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D002784:Cholesterol; D003345:Corticosterone
keywords: Amygdala; Glucocorticoid receptor; Mineralocorticoid receptor; Nociception; Oligodeoxynucleotide; Rat
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