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

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.

• Authors: Anke Tappe-Theodor, Yu Fu, Rohini Kuner, Volker Neugebauer
• Journal: Molecular pain (Mol Pain) Vol. 7 Pg. 38 (May 19 2011) ISSN: 1744-8069 [Electronic] United States
• PMID: 21595930 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Homer Scaffolding Proteins
• Homer1 protein, mouse
• Homer1 protein, rat
• Receptors, Metabotropic Glutamate
• metabotropic glutamate receptor type 1

Topics

• Amygdala (metabolism, physiopathology)
• Animals
• Behavior, Animal (physiology)
• Carrier Proteins (metabolism)
• Homer Scaffolding Proteins
• Mice
• Mice, Transgenic
• Neuronal Plasticity (physiology)
• Pain (metabolism, physiopathology)
• Rats
• Receptors, Metabotropic Glutamate (metabolism)
• Synapses (physiology)
• Synaptic Transmission (physiology)