5-HT2c receptor knockdown in the amygdala inhibits neuropathic-pain-related plasticity and behaviors

Guangchen Ji, Wei Zhang, Lenin Mahimainathan, Madhusudhanan Narasimhan, Takaki Kiritoshi, Xiuzhen Fan, Jigong Wang, Thomas A. Green, Volker Neugebauer

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Neuroplasticity in the amygdala drives pain-related behaviors. The central nucleus (CeA) serves major amygdala output functions and can generate emotional-affective behaviors and modulate nocifensive responses. The CeA receives excitatory and inhibitory inputs from the basolateral nucleus (BLA) and serotonin receptor subtype 5-HT2CR in the BLA, but not CeA, has been implicated anxiogenic behaviors and anxiety disorders. Here, we tested the hypothesis that 5-HT2CR in the BLA plays a critical role in CeA plasticity and neuropathic pain behaviors in the rat spinal nerve ligation (SNL) model. Local 5-HT2CR knockdown in the BLA with stereotaxic injection of 5-HT2CR shRNA AAV vector decreased vocalizations and anxiety- and depression-like behaviors and increased sensory thresholds of SNL rats, but had no effect in sham controls. Extracellular single-unit recordings of CeA neurons in anesthetized rats showed that 5-HT2CR knockdown blocked the increase in neuronal activity (increased responsiveness, irregular spike firing, and increased burst activity) in SNL rats. At the synaptic level, 5-HT2CR knockdown blocked the increase in excitatory transmission from BLA to CeA recorded in brain slices from SNL rats using whole-cell patch-clamp conditions. Inhibitory transmission was decreased by 5-HT2CR knockdown in control and SNL conditions to a similar degree. The findings can be explained by immunohistochemical data showing increased expression of 5-HT2CR in non-GABAergic BLA cells in SNL rats. The results suggest that increased 5-HT2CR in the BLA contributes to neuropathic-pain-related amygdala plasticity by driving synaptic excitation of CeA neurons. As a rescue strategy, 5-HT2CR knockdown in the BLA inhibits neuropathic-pain-related behaviors.

Original languageEnglish (US)
Pages (from-to)1378-1393
Number of pages16
JournalJournal of Neuroscience
Volume37
Issue number6
DOIs
StatePublished - Feb 8 2017

Keywords

  • Amygdala
  • Depression
  • Pain
  • Plasticity
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience(all)

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    Ji, G., Zhang, W., Mahimainathan, L., Narasimhan, M., Kiritoshi, T., Fan, X., Wang, J., Green, T. A., & Neugebauer, V. (2017). 5-HT2c receptor knockdown in the amygdala inhibits neuropathic-pain-related plasticity and behaviors. Journal of Neuroscience, 37(6), 1378-1393. https://doi.org/10.1523/JNEUROSCI.2468-16.2016