Homer1a signaling in the amygdala counteracts pain-related synaptic plasticity, mGluR1 function and pain behaviors

• Verfasst von: Tappe-Theodor, Anke [VerfasserIn]
• Verfasst von: Fu, Yu [VerfasserIn]
• Verfasst von: Kuner, Rohini [VerfasserIn]
• Verfasst von: Neugebauer, Volker [VerfasserIn]
• Titel: Homer1a signaling in the amygdala counteracts pain-related synaptic plasticity, mGluR1 function and pain behaviors
• Verf.angabe: Anke Tappe-Theodor, Yu Fu, Rohini Kuner and Volker Neugebauer
• E-Jahr: 2011
• Jahr: January 1, 2011
• Umfang: 6 S.
• Fussnoten: Gesehen am 20.10.2022
• Titel Quelle: Enthalten in: Molecular pain
• Ort Quelle: London : Sage, 2005
• Jahr Quelle: 2011
• Band/Heft Quelle: 7(2011), Artikel-ID 38, Seite 1-6
• ISSN Quelle: 1744-8069
• DOI: doi:10.1186/1744-8069-7-38
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1819535835

Abstract

Background:Group I metabotropic glutamate receptor (mGluR1/5) signaling is an important mechanism of pain-related plasticity in the amygdala that plays a key role in the emotional-affective dimension of pain. Homer1a, the short form of the Homer1 family of scaffolding proteins, disrupts the mGluR-signaling complex and negatively regulates nociceptive plasticity at spinal synapses. Using transgenic mice overexpressing Homer1a in the forebrain (H1a-mice), we analyzed synaptic plasticity, pain behavior and mGluR1 function in the basolateral amygdala (BLA) in a model of arthritis pain.Findings:In contrast to wild-type mice, H1a-mice mice did not develop increased pain behaviors (spinal reflexes and audible and ultrasonic vocalizations) after induction of arthritis in the knee joint. Whole-cell patch-clamp recordings in brain slices showed that excitatory synaptic transmission from the BLA to the central nucleus (CeA) did not change in arthritic H1a-mice but increased in arthritic wild-type mice. A selective mGluR1 antagonist (CPCCOEt) had no effect on enhanced synaptic transmission in slices from H1a-BLA mice with arthritis but inhibited transmission in wild-type mice with arthritis as in our previous studies in rats.Conclusions:The results show that Homer1a expressed in forebrain neurons, prevents the development of pain hypersensitivity in arthritis and disrupts pain-related plasticity at synapses in amygdaloid nuclei. Furthermore, Homer1a eliminates the effect of an mGluR1 antagonist, which is consistent with the well-documented disruption of mGluR1 signaling by Homer1a. These findings emphasize the important role of mGluR1 in pain-related amygdala plasticity and provide evidence for the involvement of Homer1 proteins in the forebrain in the modulation of pain hypersensitivity.