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Traumatic Stress Promotes Hyperalgesia via Corticotropin‐Releasing Factor Signaling in Central Amygdala
Author(s) -
Gilpin Nicholas,
Roltsch Emily,
Lu YiLing,
Whitaker Annie,
Baynes Brittni,
Baiamonte Brandon,
Richardson Heather
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.983.7
Subject(s) - hyperalgesia , amygdala , antagonist , context (archaeology) , medicine , endocrinology , neuroscience , psychology , nociception , receptor , biology , paleontology
Traumatic stress disorders are defined by persistent avoidance of trauma‐related stimuli, hyperarousal, and negative affect. Our lab uses a stress model in which rats are indexed for avoidance of a predator odor‐paired context, and divided into “Avoiders” (i.e., high stress reactivity) and “Non‐Avoiders” (i.e., low stress reactivity). Using this model, our lab showed that Avoiders exhibit altered prefrontal cortex‐amygdala neuronal activation profiles when exposed to stress‐paired stimuli, and that stress‐induced increases in thermal nociception are mediated by corticotropin‐releasing factor (CRF)‐1 receptors (CRF1Rs). Therefore, we hypothesized that CRF1R antagonist effects are mediated within the central amygdala (CeA). Here, we measured predator odor stress effects on CRF peptide content, transcript, and cell counts in CeA, and we also tested the role of CeA CRF1Rs in mediating stress‐induced thermal hyperalgesia. We observed higher CRF peptide content in CeA of Avoiders relative to Non‐Avoiders and Controls. Avoiders exhibited thermal hyperalgesia that was reversed by systemic antagonism of CRF1Rs; intra‐CeA tetrodotoxin abolished the CRF1R antagonist effect in Avoiders and produced hyperalgesia in Non‐Avoiders and Controls. Finally, intra‐CeA CRF produced thermal hyperalgesia, and this effect was blocked by antagonism of CRF1Rs or GABA‐A receptors in CeA. These results suggest that CRF1Rs are a promising therapeutic target for treatment of traumatic stress disorders. This work was supported by NIH grants AA018400, AA023305, and AA021013.