Contribution of AMPA Receptor-Mediated LTD in LA/BLA-CeA Pathway to Comorbid Aversive and Depressive Symptoms in Neuropathic Pain
| Autor: | Jing-Gui Song, Xiao-Mei Yang, Ling-Yu Kong, You Wan, Jie Cai, Jiang-Ping Liu, Xi-Yuan Han, Guo-Gang Xing, Ke Xi, Si-Qing Cai, Hong Jiang, Ling-Yu Liu |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Patch-Clamp Techniques Dendritic spine Conditioning Classical Emotions Genetic Vectors Comorbidity AMPA receptor Anxiety Amygdala Rats Sprague-Dawley Synapse Food Preferences Neuroplasticity Avoidance Learning Animals Medicine Single-Blind Method Receptors AMPA Ligation Research Articles Swimming Sensitization Basolateral Nuclear Complex Depression business.industry Long-Term Synaptic Depression General Neuroscience Central Amygdaloid Nucleus Lentivirus Chronic pain Excitatory Postsynaptic Potentials medicine.disease Endocytosis Rats Spinal Nerves medicine.anatomical_structure Hyperalgesia Rotarod Performance Test Neuropathic pain Exploratory Behavior Neuralgia Peptides business Neuroscience |
| Zdroj: | J Neurosci |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2678-20.2021 |
| Popis: | Comorbid anxiety and depressive symptoms in chronic pain are a common health problem, but the underlying mechanisms remain unclear. Previously, we have demonstrated that sensitization of the CeA neurons via decreased GABAergic inhibition contributes to anxiety-like behaviors in neuropathic pain rats. In this study, by using male Sprague Dawley rats, we reported that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain. Bilateral electrolytic lesions of CeA, but not lateral/basolateral nucleus of the amygdala (LA/BLA), abrogated both pain hypersensitivity and aversive and depressive symptoms of neuropathic rats induced by spinal nerve ligation (SNL). Moreover, SNL rats showed structural and functional neuroplasticity manifested as reduced dendritic spines on the CeA neurons and enhanced LTD at the LA/BLA-CeA synapse. Disruption of GluA2-containing AMPAR trafficking and endocytosis from synapses using synthetic peptides, either pep2-EVKI or Tat-GluA2((3Y)), restored the enhanced LTD at the LA/BLA-CeA synapse, and alleviated the mechanical allodynia and comorbid aversive and depressive symptoms in neuropathic rats, indicating that the endocytosis of GluA2-containing AMPARs from synapses is probably involved in the LTD at the LA/BLA-CeA synapse and the comorbid aversive and depressive symptoms in neuropathic pain in SNL-operated rats. These data provide a novel mechanism for elucidating comorbid aversive and depressive symptoms in neuropathic pain and highlight that structural and functional neuroplasticity in the amygdala may be important as a promising therapeutic target for comorbid negative emotional-affective disorders in chronic pain. SIGNIFICANCE STATEMENT Several studies have demonstrated the high comorbidity of negative affective disorders in patients with chronic pain. Understanding the affective aspects related to chronic pain may facilitate the development of novel therapies for more effective management. Here, we unravel that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain, and LTD at the amygdaloid LA/BLA-CeA synapse mediated by GluA2-containing AMPAR endocytosis underlies the comorbid aversive and depressive symptoms in neuropathic pain. This study provides a novel mechanism for elucidating comorbid aversive and depressive symptoms in neuropathic pain and highlights that structural and functional neuroplasticity in the amygdala may be important as a promising therapeutic target for comorbid negative emotional-affective disorders in chronic pain. |
| Databáze: | OpenAIRE |
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