Acquisition of analgesic properties by the cholecystokinin (CCK)/CCK2 receptor system within the amygdala in a persistent inflammatory pain condition.
Amygdala
/ metabolism
Animals
Cholecystokinin
/ metabolism
Dark Adaptation
/ drug effects
Disease Models, Animal
Exploratory Behavior
/ drug effects
Freund's Adjuvant
/ toxicity
Gastrins
/ therapeutic use
Glutamate Decarboxylase
/ metabolism
Inflammation
/ chemically induced
Male
Neurons
/ drug effects
Nociception
/ drug effects
Pain
/ etiology
Pain Threshold
/ drug effects
Periaqueductal Gray
/ drug effects
Rats
Rats, Sprague-Dawley
Receptor, Cholecystokinin B
/ agonists
Signal Transduction
/ drug effects
Sincalide
/ therapeutic use
Tetragastrin
/ analogs & derivatives
Journal
Pain
ISSN: 1872-6623
Titre abrégé: Pain
Pays: United States
ID NLM: 7508686
Informations de publication
Date de publication:
Feb 2019
Feb 2019
Historique:
pubmed:
4
10
2018
medline:
27
6
2019
entrez:
4
10
2018
Statut:
ppublish
Résumé
Pain is associated with negative emotions such as anxiety, but the underlying neurocircuitry and modulators of the association of pain and anxiety remain unclear. The neuropeptide cholecystokinin (CCK) has both pronociceptive and anxiogenic properties, so we explored the role of CCK in anxiety and nociception in the central amygdala (CeA), a key area in control of emotions and descending pain pathways. Local infusion of CCK into the CeA of control rats increased anxiety, as measured in the light-dark box test, but had no effect on mechanical sensitivity. By contrast, intra-CeA CCK infusion 4 days after Complete Freund's Adjuvant (CFA) injection into the hindpaw resulted in analgesia, but also in loss of its anxiogenic capacity. Inflammatory conditions induced changes in the CeA CCK signaling system with an increase of CCK immunoreactivity and a decrease in CCK1, but not CCK2, receptor mRNA. In CFA rats, patch-clamp experiments revealed that CCK infusion increased CeA neuron excitability. It also partially blocked the discharge of wide dynamic range neurons in the dorsal spinal cord. These effects of CCK on CeA and spinal neurons in CFA rats were mimicked by the specific CCK2 receptor agonist, gastrin. This analgesic effect was likely mediated by identified CeA neurons projecting to the periaqueductal gray matter that express CCK receptors. Together, our data demonstrate that intra-CeA CCK infusion activated a descending CCK2 receptor-dependent pathway that inhibited spinal neuron discharge. Thus, persistent pain induces a functional switch to a newly identified analgesic capacity of CCK in the amygdala, indicating central emotion-related circuit controls pain transmission in spinal cord.
Identifiants
pubmed: 30281531
doi: 10.1097/j.pain.0000000000001408
pii: 00006396-201902000-00008
doi:
Substances chimiques
Gastrins
0
Receptor, Cholecystokinin B
0
Tetragastrin
0OL293AV80
A 71623
130408-77-4
Freund's Adjuvant
9007-81-2
Cholecystokinin
9011-97-6
gastrin I
9045-90-3
Glutamate Decarboxylase
EC 4.1.1.15
glutamate decarboxylase 1
EC 4.1.1.15
Sincalide
M03GIQ7Z6P
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
345-357Références
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