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<p><sup>AMPA receptors (AMPARs) are key molecular mediators of fast excitatory neurotransmission and synaptic plasticity in the central nervous system. Increasing evidence indicates that maladaptive regulation of AMPAR trafficking, subunit composition, and phosphorylation contributes to central sensitization underlying chronic pain. Experimental models demonstrate that inflammation or nerve injury induces GluA2 internalization and insertion of calcium-permeable AMPARs in the spinal dorsal horn and supraspinal regions, such as the anterior cingulate cortex, insula, amygdala, and nucleus accumbens. These alterations enhance excitatory transmission and sustain pain perception. Translational advances in molecular neuroimaging have enabled visualization of such mechanisms in vivo. The positron emission tomography (PET) radioligand [11C]K-2 allows quantitative mapping of AMPAR density in the human brain, while FDG-PET captures pain-related metabolic abnormalities within the pain matrix, including the anterior cingulate, insula, and thalamus. Integrating AMPAR-PET with MRI provides a multiscale framework linking molecular receptor dynamics with network-level reorganization. Furthermore, longitudinal PET and MRI studies demonstrate partial reversibility of structural and functional brain alterations following effective treatments, suggesting that pain-related neuroplasticity is modifiable. These insights highlight the potential of AMPAR-targeted imaging biomarkers to objectively characterize chronic pain mechanisms, guide therapeutic stratification, and evaluate treatment response. Establishing standardized multimodal imaging protocols and large collaborative databases will be essential to translate these discoveries into mechanism-based diagnostics and interventions for chronic pain</sup><sup>.</sup></p>

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AMPA receptor, neuroimaging, and chronic pain

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月11日

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  • Yu Sakai,
  • Morihiko Kawate,
  • Kenta Wakaizumi,
  • Tomoyuki Miyazaki

摘要

AMPA receptors (AMPARs) are key molecular mediators of fast excitatory neurotransmission and synaptic plasticity in the central nervous system. Increasing evidence indicates that maladaptive regulation of AMPAR trafficking, subunit composition, and phosphorylation contributes to central sensitization underlying chronic pain. Experimental models demonstrate that inflammation or nerve injury induces GluA2 internalization and insertion of calcium-permeable AMPARs in the spinal dorsal horn and supraspinal regions, such as the anterior cingulate cortex, insula, amygdala, and nucleus accumbens. These alterations enhance excitatory transmission and sustain pain perception. Translational advances in molecular neuroimaging have enabled visualization of such mechanisms in vivo. The positron emission tomography (PET) radioligand [11C]K-2 allows quantitative mapping of AMPAR density in the human brain, while FDG-PET captures pain-related metabolic abnormalities within the pain matrix, including the anterior cingulate, insula, and thalamus. Integrating AMPAR-PET with MRI provides a multiscale framework linking molecular receptor dynamics with network-level reorganization. Furthermore, longitudinal PET and MRI studies demonstrate partial reversibility of structural and functional brain alterations following effective treatments, suggesting that pain-related neuroplasticity is modifiable. These insights highlight the potential of AMPAR-targeted imaging biomarkers to objectively characterize chronic pain mechanisms, guide therapeutic stratification, and evaluate treatment response. Establishing standardized multimodal imaging protocols and large collaborative databases will be essential to translate these discoveries into mechanism-based diagnostics and interventions for chronic pain.