Activation of ventrolateral orbital cortex improves mouse neuropathic pain-induced anxiodepression.
JCI Insight
; 5(19)2020 10 02.
Article
em En
| MEDLINE
| ID: mdl-33004687
ABSTRACT
Depression and anxiety are frequently observed in patients suffering from neuropathic pain. The underlying mechanisms remained unclear. The ventrolateral orbital cortex (VLO) has attracted considerable interest in its role in antidepressive effect in rodents. In the present study, we further investigated the role of the VLO in the anxiodepressive consequences of neuropathic pain in a chronic constriction injury of infraorbital nerve-induced trigeminal neuralgia (TN) mouse model. Elevated plus maze, open field, forced swimming, tail suspension, and sucrose preference tests were used to evaluate anxiodepressive-like behaviors. The results show that chemogenetic activation of bilateral VLO neurons, especially CaMK2A+ pyramidal neurons, blocked the TN-induced anxiodepressive-like behaviors. Chemogenetic and optogenetic activation of VGLUT2+ or inhibition of VGAT+ VLO neurons was sufficient to produce an antianxiodepressive effect in TN mice. Pharmacological activation of D1-like receptors (D1Rs) but not D2Rs in the VLO significantly alleviated TN-induced depressive-like behaviors. Electrophysiological recordings revealed a decreased excitability of VLO excitatory neurons following neuropathic pain. Furthermore, activation of submedius thalamic nucleus-VLO (Sm-VLO) projection mimicked the antianxiodepressive effect of VLO excitation. Conversely, activation of VLO-periaqueductal gray matter (PAG) projection had no effect on TN-induced anxiodepressive behaviors. This study provides a potentially novel mechanism-based therapeutic strategy for the anxiodepressive consequences of neuropathic pain.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ansiedade
/
Córtex Pré-Frontal
/
Transportador de Glucose Tipo 2
/
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina
/
Optogenética
/
Antidepressivos
/
Neuralgia
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China