# Top-down descending modulation of dorsal spinal excitatory transmission from the insular cortex

**Authors:** Qi-Yu Chen, Ren-Hao Liu, Shiwen Xue, Min Zhuo

PMC · DOI: 10.1177/17448069261428918 · 2026-02-20

## TL;DR

This study explores how the insular cortex influences spinal cord activity, finding mixed effects on excitatory transmission.

## Contribution

The study identifies a direct projection from the insular cortex to the spinal cord and reveals non-uniform modulation effects.

## Key findings

- IC stimulation delayed inhibition of spontaneous excitatory transmission in some spinal neurons.
- IC activation did not significantly alter the spinal nociceptive tail-flick reflex.
- The IC's top-down modulation differs from the consistently facilitatory ACC-spinal cord projection.

## Abstract

The insular cortex (IC), a critical hub for nociception, emotion, and cognition processing, has emerged as a key role in the descending modulation of spinal cord excitability. Although previous studies have suggested that IC may influence spinal nociceptive reflexes through direct or indirect top-down pathways, the specific effects of IC stimulation on spinal nociceptive transmission remain unclear. In this study, by combining in vivo whole-cell patch-clamp, behavioral and morphological approaches, we identified a direct projection from the IC to the contralateral dorsal spinal cord. To determine whether IC activation affect the spinal nociceptive reflex, we measured the spinal nociceptive tail-flick (TF) reflex during IC stimulation. We found that activating the IC by electric stimulation did not significantly alter the spinal TF reflex. Furthermore, in vivo whole-cell patch-clamp recordings from spinal dorsal horn neurons revealed that IC stimulation produced delayed inhibition of spontaneous excitatory transmission in some neurons, while exciting or having no significant effect on others. These results indicate that the top-down modulation from the IC to the spinal cord is not uniformly facilitatory, distinguishing it from the consistently facilitatory effects observed in the anterior cingulate cortex (ACC)–spinal cord projection.

## Full-text entities

- **Genes:** Sds (serine dehydratase) [NCBI Gene 25044] {aka RATSDHE1, SDH2, Sdh, Sdhe1, TDH}, RIC8B (RIC8 guanine nucleotide exchange factor B) [NCBI Gene 55188] {aka RIC8, hSyn}
- **Diseases:** pain (MESH:D010146), chronic pain (MESH:D059350), neuropsychiatric disorders (MESH:D001523), ORCID iDs (MESH:C535742), anxiety (MESH:D001007), nociceptive hypersensitivity (MESH:D004342), hyperalgesia (MESH:D006930), ACC (MESH:D017034), analgesia (MESH:D000699), depression (MESH:D003866), tissue injury (MESH:D017695)
- **Chemicals:** halothane (MESH:D006221), DAPI (MESH:C007293), MgCl2 (MESH:D015636), CO2 (MESH:D002245), NaHCO3 (MESH:D017693), KOH (MESH:C029943), ATP (MESH:D000255), CaCl2 (MESH:D002122), biotin (MESH:D001710), NaCl (MESH:D012965), glucose (MESH:D005947), HEPES (MESH:D006531), Mg (MESH:D008274), EGTA (MESH:D004533), isoflurane (MESH:D007530), GABA (MESH:D005680), Ca2+ (-), urethane (MESH:D014520), glutamate (MESH:D018698), KCl (MESH:D011189)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13009838/full.md

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Source: https://tomesphere.com/paper/PMC13009838