RT Journal Article
T1 Chemogenetic Silencing of the Locus Coeruleus-Basolateral Amygdala Pathway Abolishes Pain-Induced Anxiety and Enhanced Aversive Learning in Rats.
A1 Llorca-Torralba, Meritxell
A1 Suarez-Pereira, Irene
A1 Bravo, Lidia
A1 Camarena-Delgado, Carmen
A1 Garcia-Partida, Jose Antonio
A1 Mico, Juan Antonio
A1 Berrocoso, Esther
K1 Anxiety
K1 Aversive memory
K1 Basolateral amygdala
K1 Cognition
K1 Locus coeruleus
K1 Neuropathic pain
AB Pain affects both sensory and emotional aversive responses, often provoking anxiety-related diseases when chronic. However, the neural mechanisms underlying the interactions between anxiety and chronic pain remain unclear. We characterized the sensory, emotional, and cognitive consequences of neuropathic pain (chronic constriction injury) in a rat model. Moreover, we determined the role of the locus coeruleus (LC) neurons that project to the basolateral amygdala (BLA) using a DREADD (designer receptor exclusively activated by designer drugs). Chronic constriction injury led to sensorial hypersensitivity in both the short term and long term. Otherwise, long-term pain led to an anxiety-like profile (in the elevated zero maze and open field tests), as well as increased responses to learn aversive situations (in the passive avoidance and fear conditioning tests) and an impairment of nonemotional cognitive tasks (in the novel object recognition and object pattern of separation tests). Chemogenetic blockade of the LC-BLA pathway and intra-BLA or systemic antagonism of beta-adrenergic receptors abolished both long-term pain-induced anxiety and enhanced fear learning. By contrast, chemogenetic activation of this pathway induced anxiety-like behaviors and enhanced the aversive learning and memory index in sham animals, although it had little effect on short- and long-term chronic constriction injury animals. Interestingly, modulation of LC-BLA activity did not modify sensorial perception or episodic memory. Our results indicate that dimensions associated with pain are processed by independent pathways and that there is an overactivation of the LC-BLA pathway when anxiety and chronic pain are comorbid, which involves the activity of beta-adrenergic receptors.
PB Elsevier
YR 2019
FD 2019-02-19
LK http://hdl.handle.net/10668/13835
UL http://hdl.handle.net/10668/13835
LA en
NO Llorca-Torralba M, Suárez-Pereira I, Bravo L, Camarena-Delgado C, Garcia-Partida JA, Mico JA, et al. Chemogenetic Silencing of the Locus Coeruleus-Basolateral Amygdala Pathway Abolishes Pain-Induced Anxiety and Enhanced Aversive Learning in Rats. Biol Psychiatry. 2019 Jun 15;85(12):1021-1035
NO This study was supported by grants cofinanced by “Fondo Europeo deDesarrollo Regional” (FEDER)-UE “A way to build Europe” from the“Ministerio de Economía y Competitividad” (MINECO) (SAF2015-68647-R) and “Ministerio de Salud-Instituto de Salud Carlos III (PI18/01691);the “Consejería de Salud de la Junta de Andalucía” (PI-0134-2018); the“Programa Operativo de Andalucía FEDER, Iniciativa Territorial Integrada ITI 2014-2020 Consejería Salud, Junta de Andalucía” (PI-0080-2017); the “Consejería de Economía, Innovación, Ciencia y Empleo dela Junta de Andalucía” (CTS-510); the “Centro de Investigación Biomédica en Red de Salud Mental-CIBERSAM” (CB/07/09/0033); a YoungInvestigator Grant from the Brain Behavior Research Foundation(NARSAD23982).
DS RISalud
RD Apr 19, 2025