| RRC ID |
86393
|
| 著者 |
Shinotsuka S, I E, Sueto D, Fujimori K, Yamaura K, Tsuda M.
|
| タイトル |
Spinal Dorsal Horn Neurons Receiving Descending Input from the Primary Somatosensory Cortex Contribute to Aβ Fiber-Induced Neuropathic Allodynia in Male Rats.
|
| ジャーナル |
Cells
|
| Abstract |
Mechanical allodynia is the predominant symptom of neuropathic pain following peripheral nerve injury (PNI) and is characterized by pain evoked by innocuous sensory signals transmitted through low-threshold mechanoreceptive primary afferents, including Aβ fibers. However, the underlying neural mechanisms remain insufficiently understood. Previous studies have suggested that the pathological conversion of tactile input into nociceptive signals involves maladaptive alterations in neural circuits and function within the spinal dorsal horn (SDH). Somatosensory processing and transmission in the SDH are regulated not only by local neuronal circuits but also by descending inputs from the brainstem and higher cortical regions. In this study, we show that chemogenetic silencing of descending neurons projecting directly from the primary somatosensory (S1) cortex to the SDH (S1→SDH neurons) suppresses both PNI-induced allodynia-like behavior and c-FOS expression in the superficial SDH observed in male rats where touch-sensing Aβ fibers were optogenetically activated. S1→SDH neurons were excitatory and preferentially targeted excitatory SDH neurons (S1→SDH neurons) broadly distributed across laminae I-V. S1→SDH neurons in the superficial laminae also received excitatory inputs from both Aβ fibers and inhibitory inputs from neuropeptide Y promoter active SDH neurons (NpyP+ neurons). Furthermore, loss of inhibition from NpyP+ neurons induced Aβ fiber-derived allodynia, which was attenuated by suppressing descending signaling from S1→SDH neurons to the SDH. Moreover, silencing S1→SDH neurons alleviated neuropathic allodynia. These findings identify a new corticospinal mechanism that contributes to Aβ fiber-mediated neuropathic allodynia and highlight the S1→SDH pathway as a potential therapeutic target.
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| 巻・号 |
14(23)
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| 公開日 |
2025-11-26
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| DOI |
10.3390/cells14231870
|
| PII |
cells14231870
|
| PMID |
41369359
|
| PMC |
PMC12691292
|
| MeSH |
Animals
Hyperalgesia* / pathology
Hyperalgesia* / physiopathology
Male
Nerve Fibers* / metabolism
Neuralgia* / metabolism
Neuralgia* / pathology
Neuralgia* / physiopathology
Posterior Horn Cells* / metabolism
Posterior Horn Cells* / pathology
Rats
Rats, Sprague-Dawley
Somatosensory Cortex* / pathology
Somatosensory Cortex* / physiopathology
Spinal Cord Dorsal Horn*
|
| IF |
4.366
|
| リソース情報 |
| ラット |
W-Tg(Thy1-COP4/YFP*)4Jfhy (StrainID=1072) |
