Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Cells  

Highlights: What are the main findings? Descending neuronal signaling from the primary somatosensory (S1) cortex to the spinal dorsal horn (SDH) directly contributes to Aβ fiber-derived neuropathic allodynia in male rats. Superficial SDH neurons receiving direct projections from S1 cortical neurons integrate excitatory inputs from Aβ fibers and inhibitory inputs from SDH interneurons; loss of this inhibition unmasks their excitatory influence on spinal circuits, leading to allodynia. What are the implications of the main findings? This study demonstrates that an aberrant brain–spinal cord circuit involving the S1→SDH pathway underlies the pathological conversion of innocuous touch into pain. Targeting this corticospinal pathway may represent a promising therapeutic strategy for neuropathic allodynia. 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.

DOI： 10.3390/cells14231870

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Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：Research paper (other academic)   Publisher：(一社)日本小児麻酔学会  

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本ペインクリニック学会  

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本ペインクリニック学会  

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本ペインクリニック学会