Department of Neuroscience & Cell Biology, The University of Texas Medical Branch, 301 University Blvd, Galveston, Texas 77555-1069, USA.
Mol Pain. 2011 May 19;7:38. doi: 10.1186/1744-8069-7-38.
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.
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.
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.
I 型代谢型谷氨酸受体（mGluR1/5）信号转导是杏仁核中与疼痛相关的可塑性的重要机制，在疼痛的情感-情感维度中起着关键作用。 Homer1a 是 Homer1 家族支架蛋白的短形式，可破坏 mGluR 信号复合物，并负调节脊髓突触的伤害性可塑性。使用在前脑中过表达 Homer1a 的转基因小鼠（H1a-小鼠），我们在关节炎疼痛模型中分析了外侧杏仁核（BLA）中的突触可塑性、疼痛行为和 mGluR1 功能。
与野生型小鼠相比，在膝关节诱导关节炎后，H1a-小鼠没有出现疼痛行为（脊髓反射和听觉和超声发声）增加。脑片全细胞膜片钳记录显示，BLA 到中央核（CeA）的兴奋性突触传递在关节炎的 H1a-小鼠中没有改变，但在关节炎的野生型小鼠中增加。选择性 mGluR1 拮抗剂（CPCCOEt）对关节炎 H1a-BLA 小鼠切片中增强的突触传递没有影响，但与我们之前在大鼠中的研究一样，抑制了关节炎野生型小鼠中的传递。
结果表明，在前脑神经元中表达的 Homer1a 可防止关节炎中疼痛敏感性的发展，并破坏杏仁核核突触中与疼痛相关的可塑性。此外，Homer1a 消除了 mGluR1 拮抗剂的作用，这与 Homer1a 对 mGluR1 信号的众所周知的破坏一致。这些发现强调了 mGluR1 在与疼痛相关的杏仁核可塑性中的重要作用，并为 Homer1 蛋白在前脑参与调制疼痛敏感性提供了证据。
