Chinese Tuina remodels the synaptic structure in neuropathic pain rats by downregulating the expression of N-methyl D-aspartate receptor subtype 2B and postsynaptic density protein-95 in the spinal cord dorsal horn

J Tradit Chin Med. 2023 Aug;43(4):715-724. doi: 10.19852/j.cnki.jtcm.20221214.002.

Abstract

Objective: To investigate whether the Chinese massage system, Tuina, exerts analgesic effects in a rat model of chronic constriction injury (CCI) by remodeling the synaptic structure in the spinal cord dorsal horn (SCDH).

Methods: Sixty-nine male Sprague-Dawley rats were randomly and evenly divided into the normal group, sham group, CCI group, CCI + Tuina group, CCI + MK-801 [an -methyl D-aspartate receptor subtype 2B (NR2B) antagonist] group, and CCI + MK-801 + Tuina group. The neuropathic pain model was established using CCI with right sciatic nerve ligation. Tuina was administered 4 d after CCI surgery, using pressing manipulation for 10 min, once daily. Motor function was observed with the inclined plate test, and pain behaviors were observed by the Von Frey test and acetone spray test. At 19 d after surgery, the L3-L5 spinal cord segments were removed. Glutamate, interleukin 1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of NR2B and postsynaptic density protein-95 (PSD-95) were detected by Western blot, and the synaptic structure was observed by transmission electron microscopy (TEM).

Results: CCI reduced motor function and caused mechanical and cold allodynia in rats, increased glutamate concentration and TNF-α and IL-1β levels, and increased expression of synapse-related proteins NR2B and PSD-95 in the SCDH. TEM revealed that the synaptic structure of SCDH neurons was altered. Most of these disease-induced changes were reversed by Tuina and intrathecal injection of MK-801 ( < 0.05 or < 0.01). For the majority of experiments, no significant differences were found between the CCI + MK-801 and CCI + MK-801 + Tuina groups.

Conclusions: Chinese Tuina can alleviate pain by remodeling the synaptic structure, and NR2B and PSD-95 receptors in the SCDH may be among its targets.

Keywords: Chinese Tuina; disks large homolog 4 protein; neuralgia; neuronal plasticity; receptors, N-Methyl-D-aspartate; spinal cord dorsal horn.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disks Large Homolog 4 Protein* / genetics
  • Disks Large Homolog 4 Protein* / metabolism
  • Dizocilpine Maleate / pharmacology
  • Glutamates / metabolism
  • Male
  • Massage* / methods
  • Neuralgia* / drug therapy
  • Neuralgia* / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate* / genetics
  • Receptors, N-Methyl-D-Aspartate* / metabolism
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord Dorsal Horn / metabolism
  • Spinal Cord Dorsal Horn / pathology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Disks Large Homolog 4 Protein
  • Dizocilpine Maleate
  • Glutamates
  • postsynaptic density proteins
  • Tumor Necrosis Factor-alpha
  • NR2B NMDA receptor
  • Dlg4 protein, rat
  • Receptors, N-Methyl-D-Aspartate