Traumatic Stress Promotes Hyperalgesia via Corticotropin-Releasing Factor-1 Receptor (CRFR1) Signaling in Central Amygdala

Autor: Annie M. Whitaker, Christy A. Itoga, Brandon A. Baiamonte, Heather N. Richardson, Brittni B. Baynes, Emily A. Roltsch Hellard, Yi-Ling Lu, Allyson L. Schreiber, Nicholas W. Gilpin
Rok vydání: 2016
Předmět:
Male
Pain Threshold
0301 basic medicine
medicine.medical_specialty
Corticotropin-Releasing Hormone
Context (language use)
Receptors
Corticotropin-Releasing Hormone
Amygdala
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
Conditioning
Psychological
Avoidance Learning
medicine
Noxious stimulus
Animals
RNA
Messenger
Rats
Wistar
Pain Measurement
Neurons
Pharmacology
Analysis of Variance
Dose-Response Relationship
Drug
business.industry
Central Amygdaloid Nucleus
Chronic pain
Antagonist
medicine.disease
Rats
Disease Models
Animal
Psychiatry and Mental health
Pyrimidines
030104 developmental biology
medicine.anatomical_structure
Nociception
Endocrinology
chemistry
Hyperalgesia
Odorants
Tetrodotoxin
Original Article
medicine.symptom
business
Neuroscience
Stress
Psychological
030217 neurology & neurosurgery
Signal Transduction
Zdroj: Neuropsychopharmacology. 41:2463-2472
ISSN: 1740-634X
0893-133X
DOI: 10.1038/npp.2016.44
Popis: Hyperalgesia is an exaggerated response to noxious stimuli produced by peripheral or central plasticity. Stress modifies nociception, and humans with post-traumatic stress disorder (PTSD) exhibit co-morbid chronic pain and amygdala dysregulation. Predator odor stress produces hyperalgesia in rodents. Systemic blockade of corticotropin-releasing factor (CRF) type 1 receptors (CRFR1s) reduces stress-induced thermal hyperalgesia. We hypothesized that CRF-CRFR1 signaling in central amygdala (CeA) mediates stress-induced hyperalgesia in rats with high stress reactivity. Adult male Wistar rats were exposed to predator odor stress in a conditioned place avoidance paradigm and indexed for high (Avoiders) and low (Non-Avoiders) avoidance of predator odor-paired context, or were unstressed Controls. Rats were tested for the latency to withdraw hindpaws from thermal stimuli (Hargreaves test). We used pharmacological, molecular, and immunohistochemical techniques to assess the role of CRF-CRFR1 signaling in CeA in stress-induced hyperalgesia. Avoiders exhibited higher CRF peptide levels in CeA that did not appear to be locally synthesized. Intra-CeA CRF infusion mimicked stress-induced hyperalgesia. Avoiders exhibited thermal hyperalgesia that was reversed by systemic or intra-CeA injection of a CRFR1 antagonist. Finally, intra-CeA infusion of tetrodotoxin produced thermal hyperalgesia in unstressed rats and blocked the anti-hyperalgesic effect of systemic CRFR1 antagonist in stressed rats. These data suggest that rats with high stress reactivity exhibit hyperalgesia that is mediated by CRF-CRFR1 signaling in CeA.
Databáze: OpenAIRE
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