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

Sep 30, 2026

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Tuina shows clinical efficacy for neuropathic pain caused by peripheral nerve injury, yet the molecular mechanisms are not fully understood. Synaptic plasticity in the spinal dorsal horn drives pain processing and astrocytes are central regulators. This study tested whether Tuina modulates astrocytic NDRG2 and GLT-1 to suppress aberrant synaptic plasticity. In a chronic constriction injury rat model, Tuina or fluorocitrate reduced pain hypersensitivity, astrocytic activation, glutamate accumulation, and synaptic plasticity-related protein alterations. Effects depended on inhibition of astrocytic NDRG2 and increased GLT-1 expression; NDRG2 overexpression impaired Tuina’s glutamate transport and analgesic benefit.

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CategoryHealthcare

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Abstract

Introduction

Journal of Cellular and Molecular Medicine ORIGINAL ARTICLE OPEN ACCESS Tuina Inhibits Synaptic Plasticity Through the Astrocytic NDRG2/GLT-1 Pathway to Alleviate Neuropathic Pain Huanzhen Zhang1,2 | Lechun Chen1,2 | Jingjing Jiang1 | Limei Huang1 | Hongye Huang1,2 | Lanting Huang3 | Shuijin Chen1,2 | Zhigang Lin1,2 1Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, China | 2Fujian Key Laboratory of Rehabilitation Technology, Fuzhou, China | 3Fujian University of Traditional Chinese Medicine, Fuzhou, China Correspondence: Shuijin Chen ([fujiantuina@126.com](fujiantuina@126.com)) | Zhigang Lin ([drlzg2014@126.com](drlzg2014@126.com)) Received: 8 October 2025 | Revised: 13 December 2025 | Accepted: 23 December 2025 Keywords: astrocytes | NDRG2/GLT-1 | neuropathic pain | synaptic plasticity | Tuina ABSTRACT While Tuina has demonstrated clinical efficacy in alleviating neuropathic pain (NP) induced by peripheral nerve injury, the underlying molecular mechanisms remain unclear. Synaptic plasticity in the spinal dorsal horn (SDH) is a key regulator of pain processing, wherein astrocytes play a central role. Regulation of N-myc downstream-regulated gene 2 (NDRG2) and glutamate transporter 1 (GLT-1) is particularly important in NP modulation. Accumulating evidence suggests that Tuina exerts analgesic effects by inhibiting aberrant synaptic plasticity. This study explored whether Tuina regulates synaptic plasticity through astrocytes to attenuate NP. Using an in vivo model, Tuina or the astrocytic inhibitor fluorocitrate was administered to a chronic constriction injury (CCI)-induced NP rat model for 14 days. Tuina significantly alleviated pain hypersensitivity in CCI rats, improved structural damage, suppressed astrocytic activation, reduced glutamate accumulation and restored the SDH's expression of proteins linked to synaptic plasticity. These effects were associated with inhibition of astrocytic NDRG2 and upregulation of GLT-1. Conversely, NDRG2 overexpression through AAV impaired Tuina's ability to promote glutamate transport, leading to glutamate accumulation, enhanced excitatory transmission and reduced analgesic efficacy. In conclusion, Tuina alleviates NP by modulating the astrocytic NDRG2/GLT-1 pathway, reducing synaptic glutamate levels and normalising synaptic plasticity. These findings provide new mechanistic insights into Tuina's analgesic action and have identified NDRG2/GLT-1 as a possible therapeutic target for NP treatment. 1 | Introduction Neuropathic pain (NP), which usually presents as a chronic, recurrent and refractory illness, is characterised by spontaneous pain, hyperalgesia, and allodynia [1] . Epidemiological data suggest that NP affects 7%–10% of the population and constitutes 20%–25% of chronic pain cases. Its high prevalence, coupled with limited treatment efficacy, presents a major public health challenge [2] . First-line pharmacological options, such as gabapentin and tricyclic antidepressants, often provide only partial relief and are limited by adverse central nervous system effects. This has spurred the need for safer and more effective alternatives. Among these, physical therapies such as thermotherapy for analgesia and relaxation, electromagnetic therapies for neuromodulation and photobiomodulation for tissue repair, alongside mechanical interventions such as traction, have been integrated into clinical practice with demonstrated benefits for some patients [3] . Nonetheless, their effectiveness varies substantially across individuals, which restricts broad applicability. Therefore, developing more comprehensive and multidimensional approaches to NP management remains crucial. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2026 The Author(s). Journal of Cellular and

FAQs

What is the main question this study investigates about Tuina?

Whether Tuina regulates synaptic plasticity through astrocytes to attenuate neuropathic pain.

How was Tuina tested in the experiment?

Tuina (or the astrocytic inhibitor fluorocitrate) was administered for 14 days in a chronic constriction injury (CCI)-induced neuropathic pain rat model.

What role do NDRG2 and GLT-1 play in the proposed mechanism?

Tuina reduces neuropathic pain by inhibiting astrocytic NDRG2 and upregulating GLT-1, which restores synaptic plasticity and lowers synaptic glutamate levels.

Sep 30, 2026

Uploaded by Patrick