Simultaneous brain-spinal fMRI reveals neural mechanisms of TENS-induced analgesia.

Authors

Zhaoxing Wei, Yunyun Duan, Yupu Zhu, Xiaomin Lin, Leiyao Zhang, Ming Zhang, Jonathan C W Brooks, Yaou Liu, Li Hu, Yazhuo Kong

Published in

Journal of advanced research. Oct 28, 2026. Epub Oct 28, 2026.

Abstract

Transcutaneous electrical nerve stimulation (TENS) can produce analgesia, but its associated cortical, brainstem, and spinal response patterns in humans remain incompletely understood.
To compare the analgesic effects and associated brain-spinal response patterns of two TENS protocols: high-frequency/low-intensity and low-frequency/high-intensity stimulation.
Ninety-two healthy adults were randomized to high-frequency TENS, low-frequency TENS, or sham stimulation. Bilateral heat-pain responses were assessed using simultaneous brain-spinal functional magnetic resonance imaging (fMRI) before and after a 30-min intervention. Pain ratings, regional activation, and periaqueductal gray (PAG)-centered functional connectivity were analyzed using linear mixed-effects models with correction for multiple comparisons.
The two TENS protocols produced different spatial profiles of analgesia. High-frequency/low-intensity TENS produced treated-side analgesia relative to sham for pain intensity (β = -2.57, 95 % confidence interval [CI] [-3.26, -1.87]) and unpleasantness (β = -2.53, 95 % CI [-3.51, -1.55]). Treated-side analgesia was accompanied by reduced heat-evoked activity in the secondary somatosensory cortex (S2), PAG, rostral ventromedial medulla (RVM), and C6 spinal cord, increased ventromedial prefrontal cortex (vmPFC) activity, and altered PAG-spinal connectivity. Low-frequency/high-intensity TENS produced bilateral analgesia, reducing pain intensity on the treated and untreated sides (β = -2.07 and -1.75, respectively) and unpleasantness (β = -1.98 and -1.70, respectively). This bilateral effect was accompanied by reduced activity in primary somatosensory cortex (S1)/dorsal anterior cingulate cortex (dACC)/supplementary motor area (SMA), S2, and spinal cord, together with PAG-S1 and PAG-spinal connectivity changes.
TENS analgesia was associated with protocol-specific brain-spinal response patterns. High-frequency/low-intensity TENS produced localized analgesia with neural changes consistent with spinal and supraspinal modulation, whereas low-frequency/high-intensity TENS produced bilateral analgesia with broader PAG-sensorimotor-spinal involvement.

PMID:
42951204
Bibliographic data and abstract were imported from PubMed on 29 Oct 2026.

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