Tuina Inhibits Synaptic Plasticity Through the Astrocytic NDRG2/GLT-1 Pathway to Alleviate Neuropathic Pain

Area of Science:

• Neuroscience
• Pain Research
• Integrative Medicine

Background:

• Neuropathic pain (NP) following nerve injury is debilitating.
• The molecular mechanisms of NP, particularly involving spinal dorsal horn (SDH) synaptic plasticity and astrocytes, are not fully understood.
• Tuina, a traditional therapy, shows promise for NP, but its mechanisms require elucidation.

Purpose of the Study:

• To investigate whether Tuina regulates synaptic plasticity via astrocytes to alleviate NP.
• To explore the role of N-myc downstream-regulated gene 2 (NDRG2) and glutamate transporter 1 (GLT-1) in Tuina's analgesic effects.
• To identify potential therapeutic targets for NP.

Main Methods:

• An in vivo rat model of chronic constriction injury (CCI)-induced NP was used.
• Tuina or astrocytic inhibitor fluorocitrate was administered for 14 days.
• NDRG2 overexpression via AAV was employed to assess its impact on Tuina's efficacy.

Main Results:

• Tuina significantly reduced pain hypersensitivity, structural damage, and astrocytic activation in CCI rats.
• Tuina suppressed glutamate accumulation and normalized synaptic plasticity proteins in the SDH.
• These effects were linked to NDRG2 inhibition and GLT-1 upregulation; NDRG2 overexpression counteracted Tuina's benefits.

Conclusions:

• Tuina alleviates NP by modulating the astrocytic NDRG2/GLT-1 pathway.
• This modulation reduces synaptic glutamate levels and normalizes synaptic plasticity.
• The NDRG2/GLT-1 pathway represents a potential therapeutic target for neuropathic pain.