Essential role of endogenous calcitonin gene‐related peptide in pain‐associated plasticity in the central amygdala. (7th September 2017)

• Record Type: Journal Article
• Authors: Shinohara, Kei; Watabe, Ayako M.; Nagase, Masashi; Okutsu, Yuya; Takahashi, Yukari; Kurihara, Hiroki; Kato, Fusao
• Is Part Of: European journal of neuroscience. Volume 46:Number 6(2017)
• Page Start: 2149
• Page End: 2160
• Publication Date: 2017-09-07
• Subjects: chronic pain -- mouse -- parabrachial nucleus -- synaptic potentiation; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.13662
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: The role of the neuropeptide calcitonin gene‐related peptide (CGRP) is well established in nociceptive behaviors. CGRP is highly expressed in the projection pathway from the parabrachial nucleus to the laterocapsular region of the central amygdala (CeC), which plays a critical role in relaying nociceptive information. The CeC is a key structure in pain behavior because it integrates and modulates nociceptive information along with other sensory signals. Previous studies have demonstrated that blockade of the amygdalar CGRP‐signaling cascade attenuates nociceptive behaviors in pain models, while CGRP application facilitates amygdalar synaptic transmission and induces pain behaviors. Despite these lines of evidence, it remains unclear whether endogenous CGRP is involved in the development of nociceptive behaviors accompanied with amygdalar plasticity in a peripheral inflammation model in vivo . To directly address this, we utilized a previously generated CGRP knockout (KO) mouse to longitudinally study formalin‐induced plasticity and nociceptive behavior. We found that synaptic potentiation in the right PB‐CeC pathway that was observed in wild‐type mice was drastically attenuated in the CGRP KO mice 6 h post‐inflammation, when acute nociceptive behavior was no longer observed. Furthermore, the bilateral tactile allodynia 6 h post‐inflammation was significantly decreased in the CGRP KO mice. In contrast, the acute nociceptive behavior immediately after the formalin injection was reduced only at 20–25 min post‐injection in the CGRP KO mice. These results suggest that endogenous CGRP contributes to peripheral inflammation‐induced synaptic plasticity in the amygdala, and this plasticity may underlie the exaggerated nociception–emotion linkage in pain chronification. Abstract : αCGRP knockout (CGRP KO) mice were utilized to analyze synaptic transmission and pain behaviors 6 h after formalin injection. Synaptic potentiation at the parabrachio‐amygdaloid (PB‐CeC) pathway was drastically attenuated, and bilateral tactile allodynia was significantly suppressed in the CGRP KO mice compared with their wild‐type mice. These results revealed a pivotal role of endogenous αCGRP in formalin‐induced plasticity and long‐term changes in central sensitization‐induced behaviors.