Electroacupuncture activates inhibitory neural circuits in the somatosensory cortex to relieve neuropathic pain

iScience, 2021 · DOI: https://doi.org/10.1016/j.isci.2021.102066 · Published: February 19, 2021

Alternative Medicine Neurology Pain Management

Simple Explanation

Electroacupuncture (EA) has been shown to alleviate neuropathic pain, but its effects on the brain's cortex are not well understood. This study investigates how EA affects neural circuits in the somatosensory cortex, a brain region involved in processing sensory information. The study found that EA treatment modulated the activity of neural circuits in the primary somatosensory cortex, suppressing excitatory neurons and enhancing inhibitory interneurons. This modulation was dependent on the activation of endocannabinoid receptor 1 (CB1R). These findings suggest that EA relieves neuropathic pain by modulating cortical circuits, specifically by activating the CB1R pathway, which leads to the suppression of excitatory neurons via inhibitory circuits.

Study Duration

14 days

Participants

Male C57BL/6 mice

Evidence Level

Not specified

Key Findings

1
EA treatment reduces both mechanical and thermal hypersensitivity in mice with neuropathic pain, indicating its analgesic effects.
2
EA treatment normalizes cortical inhibitory networks by suppressing VIP-INs, activating SST-INs, and subsequently inhibiting PNs.
3
The CB1R pathway is essential for EA-mediated pain relief and modulation of cortical circuits, as blocking CB1R abolishes the analgesic effects of EA.

Research Summary

This study provides in vivo evidence showing that repeated EA treatment modulates the cortical circuit to relieve neuropathic pain. The activation of CB1R by EA leads to presynaptic inhibition at GABAergic VIP axonal terminals, resulting in the disinhibition of SST-INs and the suppression of L5PNs, and eventually reducing mechanical or thermal hypersensitivity. The findings identify CB1R as the mediator in restoring cortical excitatory/inhibitory balance to ameliorate neuropathic pain after EA intervention, agreeing with previous reports of dysregulation of cortical GABAergic transmission under neuropathic pain. The established cortical neural circuit helps explain the effect of EA in reducing mechanical or thermal hypersensitivity under neuropathic pain, emphasizing the critical role of the sensory cortex in EA's analgesia.

Practical Implications

Clinical Pain Management

Acupuncture, specifically electroacupuncture, can be considered as a therapeutic intervention for managing neuropathic pain, providing a non-pharmacological approach to pain relief.

Targeted Therapies

The CB1R pathway could be a potential target for developing new analgesics or for enhancing the efficacy of acupuncture treatments.

Cortical Circuit Modulation

Understanding the cortical mechanisms of pain relief can guide the development of targeted interventions to modulate brain activity and alleviate chronic pain conditions.

Study Limitations

1
The study primarily focuses on the somatosensory cortex, leaving changes in the subcortical network unclear.
2
The data does not conclusively determine if CB1R mediates pain relief through other brain regions or peripheral nerves.
3
The study only described the modulation of local neural circuitry in the somatosensory cortex under EA intervention

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