Amygdala-mediated mechanisms regulate visceral hypersensitivity in adult females following early life stress: importance of the glucocorticoid receptor and corticotropin-releasing factor. Issue 2 (February 2017)

• Record Type: Journal Article
• Authors: Prusator, Dawn K.; Greenwood-Van Meerveld, Beverley
• Is Part Of: Pain. Volume 158:Issue 2(2017)
• Publication Date: 2017-02
• Subjects: Visceral pain -- Females -- Early life stress -- Glucocorticoid receptor -- Corticotropin-releasing factor -- Amygdala; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000000759
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Abstract: Alterations in amygdala activity are apparent in women who report a history of early life stress (ELS) and those diagnosed with chronic pain disorders. Chronic stress in adulthood induces visceral hypersensitivity by alterations in glucocorticoid receptor (GR) and corticotropin-releasing factor (CRF) expression within the central amygdala (CeA). Here, we hypothesized that unpredictable ELS, previously shown to induce visceral hypersensitivity in adult female rats, alters GR and CRF expression in the CeA. After neonatal ELS, visceral sensitivity and GR and CRF gene expression were quantified in adult female rats. After unpredictable ELS, adult female rats exhibited visceral hypersensitivity and increased expression of GR and CRF in the CeA. After predictable ELS, adult female rats demonstrated normosensitive behavioral pain responses and upregulation of GR but not CRF in the CeA. After the ELS paradigms, visceral sensitivity and gene expression within the CeA were unaffected in adult male rats. The role of GR and CRF in modulating visceral sensitivity in adult female rats after ELS was investigated using oligodeoxynucleotide sequences targeted to the CeA for knockdown of GR or CRF. Knockdown of GR increased visceral sensitivity in all rats but revealed an exaggerated visceral hypersensitivity in females with a history of predictable or unpredictable ELS compared with that of controls. Knockdown of CRF expression or antagonism of CRF1 R in the CeA attenuated visceral hypersensitivity after unpredictable ELS. This study highlights a shift in GR and CRF regulation within the CeA after ELS that underlies the development of visceral hypersensitivity in adulthood. Abstract : Unpredictable early life stress alters glucocorticoid receptor and corticotropin-releasing factor expression within the amygdala leading to the development of visceral hypersensitivity in adult female rats.