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Knockdown of steroid receptors in the central nucleus of the amygdala induces heightened pain behaviors in the rat.
Neuropharmacology 2015; 93:116-23N

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+Show Affiliations

Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.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.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

25656477

Citation

Johnson, Anthony C., and Beverley Greenwood-Van Meerveld. "Knockdown of Steroid Receptors in the Central Nucleus of the Amygdala Induces Heightened Pain Behaviors in the Rat." Neuropharmacology, vol. 93, 2015, pp. 116-23.
Johnson AC, Greenwood-Van Meerveld B. Knockdown of steroid receptors in the central nucleus of the amygdala induces heightened pain behaviors in the rat. Neuropharmacology. 2015;93:116-23.
Johnson, A. C., & Greenwood-Van Meerveld, B. (2015). Knockdown of steroid receptors in the central nucleus of the amygdala induces heightened pain behaviors in the rat. Neuropharmacology, 93, pp. 116-23. doi:10.1016/j.neuropharm.2015.01.018.
Johnson AC, Greenwood-Van Meerveld B. Knockdown of Steroid Receptors in the Central Nucleus of the Amygdala Induces Heightened Pain Behaviors in the Rat. Neuropharmacology. 2015;93:116-23. PubMed PMID: 25656477.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Knockdown of steroid receptors in the central nucleus of the amygdala induces heightened pain behaviors in the rat. AU - Johnson,Anthony C, AU - Greenwood-Van Meerveld,Beverley, Y1 - 2015/02/03/ PY - 2014/10/16/received PY - 2014/11/25/revised PY - 2015/01/21/accepted PY - 2015/2/7/entrez PY - 2015/2/7/pubmed PY - 2016/1/2/medline KW - Amygdala KW - Glucocorticoid receptor KW - Mineralocorticoid receptor KW - Nociception KW - Oligodeoxynucleotide KW - Rat SP - 116 EP - 23 JF - Neuropharmacology JO - Neuropharmacology VL - 93 N2 - 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. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/25656477/Knockdown_of_steroid_receptors_in_the_central_nucleus_of_the_amygdala_induces_heightened_pain_behaviors_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(15)00034-9 DB - PRIME DP - Unbound Medicine ER -