PKCδ-expressing cells in the central amygdala modulate tactile hypersensitivity in a mouse model of neuropathic pain
Thursday, September 15, 2016 — Poster Session III
- TD Wilson
- G Soroosh
- YG Carrasquillo
The central nucleus of the amygdala (CeA) is an area of the brain with critical roles in the modulation of pathological pain. Previous studies have shown that modulation of pain-related behaviors in the CeA is dependent on the activation of the extracellular signal regulated kinase (ERK). Experiments exploiting molecular genetic approaches have further revealed that genetically-identified neurons in the CeA have distinct functions in the modulation of behaviors. The genetic identity of the cells in the CeA that are recruited during pain and the specific functions of genetically-identified CeA cells in the modulation of pain-related behaviors, however, are unknown. The experiments here began to address these questions directly using a combination of histological, behavioral and chemogenetic approaches. The sciatic nerve cuff and the Complete Freund’s Adjuvant (CFA) rodent models of neuropathic and inflammatory pain were used to induce persistent tactile hypersensitivity. To determine the genetic identity of the CeA cells that are recruited during persistent pain, we crossed various Cre mouse lines with the Ai9 reporter line and performed immunofluorescent staining for pERK following cuff surgery or CFA paw injection. These experiments showed that pain-induced ERK activation is mostly localized to PKCδ-expressing cells within the CeA. Behavioral experiments on PKCδ-cre mice further demonstrated that chemogenetic inhibition of PKCδ–expressing cells in the CeA reverses cuff-induced tactile hypersensitivity without affecting baseline mechanical thresholds. Altogether, these results demonstrate that activation of PKCδ-expressing cells in the CeA is necessary for the modulation of tactile hypersensitivity in a mouse model of neuropathic pain.