Transcranial Ultrasound Stimulation of the Anterior Cingulate Cortex Reduces Neuropathic Pain in Mice.

Xiangjun Feng,Shasha Yi,Wei Zhou,Lili Niu,Moxian Chen,Kaixuan Luo,Xiaowei Huang,Zhengrong Lin,Meng Long,Lijuan Ao,Feng Zhang

doi:10.1155/2021/6510383

Abstract

Focused ultrasound (FUS) is a potential tool for treating chronic pain by modulating the central nervous system. Herein, we aimed to determine whether transcranial FUS stimulation of the anterior cingulate cortex (ACC) effectively improved chronic pain in the chronic compress injury mice model at different stages of neuropathic pain. The mechanical threshold of pain was recorded in the nociceptive tests. We found FUS stimulation elevated the mechanical threshold of pain in both short-term (p < 0.01) and long-term (p < 0.05) experiments. Furthermore, we determined protein expression differences in ACC between the control group, the intervention group, and the Sham group to analyze the underlying mechanism of FUS stimulation in improving neuropathic pain. Additionally, the results showed FUS stimulation led to alterations in differential proteins in long-term experiments, including cellular processes, cellular signaling, and information storage and processing. Our findings indicate FUS may effectively alleviate mechanical neuropathic pain via the ACC's stimulation, especially in the chronic state.

Highlights

Chronic pain is a severe condition that considerably interferes with daily functioning [1], and the estimated prevalence of chronic pain ranges from 8.7% to 64.4% [2, 3]
Transcranial focused ultrasound (FUS) Stimulation Slowly Improved the Mechanical Withdraw reshold in the Short-Term Experiment. e results showed an increase in the mechanical withdraw threshold of the operation side following the end of the FUS2 stimulation period (FUS1 group, 0.06 ± 0.01 g; FUS2 group, 0.32 ± 0.09 g; Sham group, 0.04 ± 0.01 g; p < 0.01 (p 0.003)), indicating that the pain tolerance of mice on the surgical side had improved
Our findings indicated that ultrasound stimulation of the anterior cingulate cortex (ACC) increased the mechanical withdraw threshold in the chronic compress injury (CCI) mice model in both the short- and long-term experiments

Summary

Introduction

Chronic pain is a severe condition that considerably interferes with daily functioning [1], and the estimated prevalence of chronic pain ranges from 8.7% to 64.4% [2, 3]. E use of the S-size ultrasound probe in pulsed mode stimulation over a skin incision has been reported to improve the mechanical and thermal retraction threshold of the NP model [7]. Erefore, focused ultrasound (FUS) may be a nonpharmacological nonablative neuromodulatory technique that improves peripheral nerve injury or NP. Hameroff et al stimulated individuals with chronic pain using transcranial ultrasound and Evidence-Based Complementary and Alternative Medicine reported an unexpected analgesic effect [9]. Spooner et al reported that deep brain stimulation over the bilateral cingulate by 130 Hz high-frequency electricity resulted in pain relief in a patient with severe drug-resistant pain syndrome following a complete spinal cord injury [10]. There has been increasing interest in modulating the central nervous system (CNS) for chronic pain treatment

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