Simultaneous brain-spinal fMRI reveals neural mechanisms of TENS-induced analgesia
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Updated: Oct 30, 2026
Monitoring Acupuncture Effects on Human Brain by fMRI
Published on: April 8, 2010
Zhaoxing Wei1, Yunyun Duan2, Yupu Zhu3
1State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China; Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA.
Introduction:
Transcutaneous electrical nerve stimulation (TENS) can produce analgesia, but its associated cortical, brainstem, and spinal response patterns in humans remain incompletely understood.
Objectives:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
