Knockdown of corticotropin-releasing factor in the central amygdala reverses persistent viscerosomatic hyperalgesia.
Gastrointestinal nociception is exacerbated by chronic stress through an unknown mechanism. The amygdala is a key nucleus involved in the autonomic and neuroendocrine responses to stress. The goal of this study was to test the hypothesis that prolonged exposure of the central amygdala (CeA) to stress or the stress hormone cortisol (or corticosterone in rats) induces nociceptive behaviors mediated by corticotropin-releasing factor (CRF) within the CeA. We selectively knocked down CRF in the CeA via antisense oligodeoxynucleotides (ASO) in animals with targeted, stereotaxically placed corticosterone (CORT) micropellets or following repeated water avoidance stress (WAS). CRF expression in the CeA was analyzed concurrently with the assessment of visceral hypersensitivity to colonic distension and mechanical somatic withdrawal threshold. The responses were characterized at 7 or 28 days post implantation of the CORT micropellet or following 7 days of WAS. Exposure of the CeA to elevated CORT or WAS increased CRF expression and heightened visceral and somatic sensitivity. Infusion of CRF ASO into the CeA decreased CRF expression and attenuated visceral and somatic hypersensitivity in both models. Our study provides important evidence for a CRF-mediated mechanism specifically within the CeA that regulates stress-induced visceral and somatic nociception.
Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
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Johnson
Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
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1] Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, USA [2] Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA [3] VA Medical Center, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
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Greenwood-Van Meerveld
D000704:Analysis of Variance; D000818:Animals; D066274:Central Amygdaloid Nucleus / Q000378:metabolism / Q000503:physiopathology*; D003345:Corticosterone / Q000009:adverse effects / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D059226:Nociceptive Pain / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D011916:Rats, Inbred F344
D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone