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

doi:10.19852/j.cnki.jtcm.20221214.002

Journal of Traditional Chinese Medicine ›› 2023, Vol. 43 ›› Issue (4): 715-724.DOI: 10.19852/j.cnki.jtcm.20221214.002

• Original Articles • Previous Articles Next Articles

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

HUANG Hongye¹, WANG Bingqian⁴, CHEN Shuijin²^,³, FANG Jiayu¹, WANG Xiaohua¹, CHEN Lechun²^,³, JIANG Yu²^,³, ZHANG Huanzhen²^,³, CHEN Jincheng²^,³, LIN Zhigang²^,³()

1 College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
2 Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital, Fuzhou 350003, China
3 Fujian Provincial Key Laboratory of Rehabilitation Technology, Fuzhou 350003, China
4 Peking University International Hospital, Beijing 102206, China

Received:2022-02-23 Accepted:2022-07-08 Online:2022-12-14 Published:2022-12-14
Contact: LIN Zhigang
About author:Dr. LIN Zhigang, Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital, Fuzhou 350003, China. linzhigang@fjtcm.edu.cn. Telephone: +86-18159191681
Supported by:
Natural Science Foundation-funded Project: Study on the Mechanism of Tuina and Tuina in Regulating the Synaptic Plasticity of Spinal Dorsal Horn in Lumbar Disc Herniation Based on LncRNA-HOTAIR/miR-219 Mediated NMDAR Pathway(82174523);Natural Science Foundation of Fujian Province: Study on the Mechanism of Tuina Regulating the Synaptic Plasticity of Spinal Dorsal Horn in Lumbar Disc Herniation based on NMDAR-CAMK2-CREB Pathway(2020J01757);Study on Analgesic Mechanism of Tuina on Neuropathic Pain in Spinal Dorsal Horn/ACC Brain Region based on PKA-NMDA-NR2B Pathway(2020J01758);Fujian Health Science and Technology Program: Study on the Analgesic Mechanism of Tuina Manipulation On Lumbar Disc Herniation from the Efficacy of miR-219/NR2B Mediated Synaptic Transmission(2020GGA070);Effects of Tuina Point Press on AMPA/NMDA Receptor Scaffold Protein and Synaptic Plasticity in Spinal Dorsal Horn of Rats with Neuropathic Pain(2020CXA052)

Abstract

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 N-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 (P < 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.

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

HUANG Hongye, WANG Bingqian, CHEN Shuijin, FANG Jiayu, WANG Xiaohua, CHEN Lechun, JIANG Yu, ZHANG Huanzhen, CHEN Jincheng, LIN Zhigang. 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]. Journal of Traditional Chinese Medicine, 2023, 43(4): 715-724.

Figures/Tables 9

Figure 1 Experimental process Inclined-plate test and Von Frey test were performed on days 4, 11, 14, 18 after CCI surgery; acetone spray test was performed on days 5, 12, 15, 19 after CCI surgery; spinal cord dorsal horn was isolated on day 19; CCI + MK-801 and CCI + MK-801 + Tuina group received intrathecal injection of MK-801 once daily from days 4-19 after CCI surgery, CCI + Tuina and CCI + MK-801 + Tuina group received Tuina treatment once daily from day 4-19 after CCI surgery. Tuina started half an hour after receiving intrathecal injection. DRG: dorsal root ganglia; CCI: chronic constriction injury; BL40: bladder meridian 40.

Figure 2 Tuina manipulation emulator with micro pressure sensor simulates the effect of Tuina manipulation on the body surface of rats A: photograph of Tuina manipulation emulator equipped with a pressure sensor and demonstration of rat fixation; B: control board can display and collect real-time mechanical information through corresponding software which can be immediately transmitted to a computer; C: real-time force display in a 15 s interval included pressing and circular rubbing manipulation (5 ± 1N).

Table 1 Inclined plate test results at different intervention times ($\bar{x}±s$)

Group	n	Baseline	Day 4	Day 11	Day 14	Day 18
Normal	5	53.7±2.2	52.7±1.9	53.3±1.7	54.0±2.8	53.3±1.7
Sham	5	51.7±1.2	45.3±1.8^a	45.7±1.9^a	50.7±2.8	50.7±3.0
CCI	5	51.7±2.0	32.7±0.9^ab	32.3±1.5^ab	34.0±1.9^ab	38.0±4.0^ab
CCI+Tuina	5	52.0±0.7	33.7±1.8	37.3±1.9^c	40.3±1.8^c	43.4±1.7
CCI+MK-801	4	51.2±0.8	34.6±1.6	36.2±1.6	41.7±1.4^c	41.2±3.5
CCI+MK-801+Tuina	5	53.0±1.4	33.0±1.4	36.0±2.2	44.0±1.5^c	45.7±3.8^d

Table 2 Time-course changes of PWTs in the hind paw of rats (g, $\bar{x}±s$)

Group	n	Baseline	Day 4	Day 11	Day 14	Day 18
Normal	5	12.0±2.7	11.6±3.2	13.0±2.7	12.0±1.2	14.0±2.2
Sham	8	11.9±2.6	11.2±2.3	12.2±3.0	11.9±2.6	13.1±2.6
CCI	8	13.1±2.6	5.0±2.4^ab	3.7±2.0^ab	3.2±1.0^ab	2.2±0.7^ab
CCI+Tuina	8	11.9±2.9	4.7±1.5	7.0±1.8^c	8.0±1.1^d	9.0±1.1^d
CCI+MK-801	8	14.2±5.6	5.5±2.1	9.0±1.1^d	9.2±1.0^d	12.5±2.7^d
CCI+MK-801+Tuina	8	14.5±5.3	4.7±2.1	9.0±1.1^d	9.4±1.6^d	11.9±2.6^d

Table 3 Time-course changes of cold spray scores in the hind paw of rats ($\bar{x}±s$)

Group	n	Baseline	Day 5	Day 12	Day 15	Day 19
Normal	5	0.80±0.14	0.76±0.17	0.60±0.14	0.62±0.06	0.48±0.23
Sham	8	0.83±0.13	0.78±0.27	0.83±0.20	0.75±0.21	0.70±0.15
CCI	8	0.88±0.15	2.73±0.15^ab	2.85±0.09^ab	2.85±0.03^ab	2.90±0.17^ab
CCI+Tuina	8	0.83±0.23	2.72±0.10	2.40±0.17	2.15±0.18^c	1.75±0.09^c
CCI+MK-801	8	0.95±0.09	1.93±0.15^c	1.45±0.14^c	1.30±0.17^c	1.13±0.10^c
CCI+MK-801+Tuina	8	0.93±0.10	1.40±0.11^cd	1.40±0.16^c	1.18±0.20^c	1.05±0.09^c

Table 4 Glutamate concentrations, TNF-α and IL-1β levels in the SCDH

Group	n	Glutamate concentrations (ng/mL)	TNF-α level (pg/100 μg)	IL-1β level (pg/100 μg)
Sham	4	726.7±34.5	16.4±1.8	186.8±11.7
CCI	4	1061.6±85.7^a	26.3±5.6^a	342.7±19.4^a
CCI+Tuina	4	807.6±14.2^b	16.3±2.0^b	227.1±7.4^b
CCI+MK-801	4	865.7±72.8^c	20.1±2.1	229.0±8.5^b
CCI+MK-801+Tuina	4	617.1±22.5^bd	18.3±2.9^c	212.5±11.3^b

Figure 3 NR2B and PSD-95 protein expression levels in the SCDH A-C: protein expression of NR2B and PSD-95 in the SCDH from rats detected by Western blot. Rats in the sham group were performed with sham surgery without knotting; the CCI group were received chronic constriction injury surgery; the CCI + Tuina group were treat with Tuina manipulation once daily; the CCI + MK-801 group were given intrathecal injection of MK-801 once daily; the CCI + MK-801 + Tuina group, the above two treatments were given once daily. Each group was treated for 14 d. CCI: chronic constriction injury; NR2B: N-methyl D-aspartate receptor subtype 2B; PSD-95: postsynaptic density protein-95; SCDH: spinal cord dorsal horn. Data were expressed as the mean ± standard error of the mean (n = 5). aP < 0.01 compared with the sham group; bP < 0.01 compared with the CCI group.

Figure 4 Synaptic ultrastructure changes and quantitative summary of synaptic ultrastructure in the SCDH (Transmission electronic microscopy staining method, × 20 000) The red arrow indicates the synapse. A: sham group; B: CCI group; C: CCI + Tuina group; D: CCI + MK-801 group; E: CCI + MK-801 + Tuina group; F: synaptic active zone length of rats in each group; G: mean PSD thickness of rats in each group; H: synaptic cleft width of rats in each group. Rats in the sham group were performed with sham surgery without knotting; the CCI group were received chronic constriction injury surgery; the CCI + Tuina group were treat with Tuina manipulation once daily; the CCI + MK-801 group were given intrathecal injection of MK-801 once daily; the CCI + MK-801 + Tuina group, the above two treatments were given once daily. Each group was treated for 14 d. SCDH: spinal cord dorsal horn; CCI: chronic constriction injury; PSD: postsynaptic density. Data were expressed as the mean ± standard error of the mean (n = 3). aP < 0.01 compared with the sham group; bP < 0.01 compared with the CCI group; cP < 0.05 compared with the CCI + MK-801 group.

Table 5 Quantitative summary of synaptic ultrastructure in the SCDH (nm)

Group	n	Active zone length	PSD thickness	Synaptic cleft
Sham	3	177.7±45.1	22.0±5.4	26.1±1.7
CCI	3	541.0±98.9^a	77.9±21.4^a	18.2±4.1^a
CCI+Tuina	3	232.5±48.1^b	25.0±6.6^b	23.8±0.7^b
CCI+MK-801	3	273.5±20.2^b	19.7±3.0^b	23.4±1.8^b
CCI+MK-801+Tuina	3	205.8±61.2^b	24.5±6.2^b	27.9±2.7^bc

References 50.

1.	Yu TY. Anmo Tuina Xue. 3rd ed. Beijing: Peking Union Medical College Press, 2012: 3-4.
2.	Wu Z, Kong L, Zhu Q, et al. Efficacy of Tuina in patients with chronic neck pain: study protocol for a randomized controlled trial. Trials 2019; 20: 1-10. DOI
3.	Zhang S, Kong L, Zhu Q, et al. Efficacy of Tuina in patients with chronic low back pain: study protocol for a randomized controlled trial. Trials 2020; 21: 1-9. DOI
4.	Ai J, Dong Y, Tian Q, et al. Tuina for periarthritis of shoulder: a systematic review protocol. Medicine 2020; 99: e19332. DOI URL
5.	Smith BH, Hébert HL, Veluchamy A. Neuropathic pain in the community: prevalence, impact, and risk factors. Pain 2020; 161: S127-37.
6.	Yan X, Weng HR. Endogenous interleukin-1β in neuropathic rats enhances glutamate release from the primary afferents in the spinal dorsal horn through coupling with presynaptic N-methyl-D-aspartic acid receptors. J Biol Chem 2013; 288: 30544-57.
7.	Liao WT, Tseng CC, Chia WT, et al. High-frequency spinal cord stimulation treatment attenuates the increase in spinal glutamate release and spinal miniature excitatory postsynaptic currents in rats with spared nerve injury-induced neuropathic pain. Brain Res Bull 2020; 164: 307-13. DOI URL
8.	Alomar SY, Gheit RE, Enan ET, et al. Novel mechanism for memantine in attenuating diabetic neuropathic pain in mice via downregulating the spinal HMGB1/TRL4/NF-kB inflammatory axis. Pharmaceuticals 2021; 14: 307. DOI URL
9.	Duarte RV, Nevitt S, McNicol E, et al. Systematic review and Meta-analysis of placebo/sham controlled randomised trials of spinal cord stimulation for neuropathic pain. Pain 2020; 161: 24-35.
10.	Berger JV, Knaepen L, Janssen SPM, et al. Cellular and molecular insights into neuropathy-induced pain hypersensitivity for mechanism-based treatment approaches. Brain Res Rev 2011; 67: 282-310. DOI PMID
11.	Peterson CD, Kitto KF, Verma H, et al. Agmatine requires GluN2B-containing NMDA receptors to inhibit the development of neuropathic pain. Mol Pain 2021; 17: 17448069211029171.
12.	Kuner R, Flor H. Structural plasticity and reorganisation in chronic pain. Nat Rev Neurosci 2017; 18: 20-30. DOI
13.	Bittar A, Jun J, La JH, et al. Reactive oxygen species affect spinal cell type-specific synaptic plasticity in a model of neuropathic pain. Pain 2017; 158: 2137-46.
14.	Liang F, Liu M, Fu X, et al. Dexmedetomidine attenuates neuropathic pain in chronic constriction injury by suppressing NR2B, NF-κB, and iNOS activation. Saudi Pharm J 2017; 25: 649-54.
15.	Lu L, Pan C, Chen L, et al. AMPK activation by peri-sciatic nerve administration of ozone attenuates CCI-induced neuropathic pain in rats. J Mol Cell Biol 2017; 9: 132-43. DOI PMID
16.	Loftis JM, Janowsky A. The N-methyl-D-aspartate receptor subunit NR2B: localization, functional properties, regulation, and clinical implications. Pharmacol Ther 2003; 97: 55-85. DOI URL
17.	Li S, Cao J, Yang X, et al. NR2B phosphorylation at tyrosine 1472 in spinal dorsal horn contributed to N‐methyl‐D‐aspartate‐induced pain hypersensitivity in mice. J Neurosci Res 2011; 89: 1869-76. DOI URL
18.	Wang XY, Zhou HR, Wang S, et al. NR2B-Tyr phosphorylation regulates synaptic plasticity in central sensitization in a chronic migraine rat model. J Headache Pain 2018; 19: 1-15.
19.	Qu XX, Cai J, Li MJ, et al. Role of the spinal cord NR2B-containing NMDA receptors in the development of neuropathic pain. Exp Neurol 2009; 215: 298-307. DOI URL
20.	Wang J, Qiao Y, Yang RS, et al. The synergistic effect of treatment with triptolide and MK-801 in the rat neuropathic pain model. Mol Pain 2017; 13: 1744806917746564.
21.	Xu F, Zhao X, Liu L, et al. Perturbing NR2B-PSD-95 interaction relieves neuropathic pain by inactivating CaMKII-CREB signaling. Neuroreport 2017; 28: 856-63. DOI PMID
22.	Wang Z, Chen Z, Yang J, et al. Treatment of secondary brain injury by perturbing postsynaptic density protein-95-NMDA receptor interaction after intracerebral hemorrhage in rats. J Cereb Blood Flow Metab 2019; 39: 1588-601. DOI URL
23.	Borja BB, Shroff H, Upadhyay H, et al. Probing synaptic signaling with optogenetic stimulation and genetically encoded calcium reporters. Methods Mol Biol 2021; 2191: 109-34. DOI PMID
24.	Huang LE, Guo SH, Thitiseranee L, et al. N-methyl D-aspartate receptor subtype 2B antagonist, Ro 25-6981, attenuates neuropathic pain by inhibiting postsynaptic density 95 expression. Sci Rep 2018; 8: 1-9.
25.	Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988; 33: 87-107.
26.	Gui X, Wang H, Wu L, et al. Botulinum toxin type A promotes microglial M2 polarization and suppresses chronic constriction injury-induced neuropathic pain through the P2X7 receptor. Cell Biosci 2020; 10: 1-10. DOI
27.	Jiang H, Yu X, Ren X, et al. Electroacupuncture alters pain-related behaviors and expression of spinal prostaglandin E_2 in a rat model of neuropathic pain. J Tradit Chin Med 2016; 36: 85-91. DOI URL
28.	Roh DH, Yoon SY, Seo HS, et al. Intrathecal injection of carbenoxolone, a gap junction decoupler, attenuates the induction of below-level neuropathic pain after spinal cord injury in rats. Exp Neurol 2010; 224: 123-32. DOI URL
29.	Rivlin AS, Tator CH. Objective clinical assessment of motor function after experimental spinal cord injury in the rat. J Neurosurg 1977; 47: 577-81.
30.	Li MJ, Liu LY, Chen L, et al. Chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala. Pain 2017; 158: 717-39.
31.	Chaplan SR, Bach FW, Pogrel JW, et al. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 1994; 53: 55-63.
32.	Vissers K, Meert T. A behavioral and pharmacological validation of the acetone spray test in gerbils with a chronic constriction injury. Anesth Analg 2005; 101: 457-64. DOI PMID
33.	Chen J, Joshi SK, DiDomenico S, et al. Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation. Pain 2011; 152: 1165-72.
34.	Park CH, Kim HW, Rhyu IJ, et al. How to get well-preserved samples for transmission electron microscopy. J Vis Exp 2016; 46: 188-92.
35.	Güldner FH, Ingham CA. Increase in postsynaptic density material in optic target neurons of the rat suprachiasmatic nucleus after bilateral enucleation. Neurosci Lett 1980; 17: 27-31. DOI PMID
36.	Jones DG, Devon RM. An ultrastructural study into the effects of pentobarbitone on synaptic organization. Brain Res 1978; 147: 47-63. PMID
37.	Wu Q, Yue J, Lin L, et al. Electroacupuncture may alleviate neuropathic pain via suppressing P2X7R expression. Mol Pain 2021; 17: 1744806921997654.
38.	Peng B, Lin J, Shang Y, et al. Plasticity in the synaptic number associated with neuropathic pain in the rat spinal dorsal horn: a stereological study. Neurosci Lett 2010; 486: 24-8. DOI PMID
39.	Xu Q, Liu T, Chen S, et al. The cumulative analgesic effect of repeated electroacupuncture involves synaptic remodeling in the hippocampal CA 3 region. Neural Regen Res 2012; 7: 1378-85.
40.	Luo H, Li Y, Shi X, et al. Ginsenoside Rd improves behavioral impairment of rats with acute plateau status by modulating synaptic plasticity. Chin Herb Med 2019; 11: 438-41.
41.	Chen LC, Lin ZG, Chen SQ, et al. Effect of Dianan massage on expression of PKC and P2X3 in dorsal root ganglion of CCI rats. Fu Jian Yi Ke Da Xue Xue Bao 2020; 54: 291-4.
42.	Lin ZG, Wang JZ, Zhao D, et al. Effects of kneading manipulation method of massage on gait and gastrocnemius of rats with chronic constriction injury of the sciatic nerve. Zhong Hua Zhong Yi Yao Za Zhi 2020; 35: 927-31.
43.	Osikowicz M, Mika J, Przewlocka B. The glutamatergic system as a target for neuropathic pain relief. Exp Physiol 2013; 98: 372-84. DOI PMID
44.	Sung B, Lim G, Mao J. Altered expression and uptake activity of spinal glutamate transporters after nerve injury contribute to the pathogenesis of neuropathic pain in rats. J Neurosci 2003; 23: 2899-910. PMID
45.	Kawasaki Y, Zhang L, Cheng JK, et al. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1β, interleukin-6, and tumor necrosis factor-α in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci 2008; 28: 5189-94.
46.	Guo W, Wang H, Watanabe M, et al. Glial-cytokine-neuronal interactions underlying the mechanisms of persistent pain. J Neurosci 2007; 27: 6006-18. PMID
47.	Deng M, Chen SR, Pan HL. Presynaptic NMDA receptors control nociceptive transmission at the spinal cord level in neuropathic pain. Cell Mol Life Sci 2019; 76: 1889-99. DOI PMID
48.	Gao YH, Chen SP, Wang JY, et al. Effects of electroacupuncture at different acupoints on the pain behavior and NMDA receptor 2 B subunit mRNA and protein expression and phosphorylation level in the cervical spinal cord in rats with thyroid regional pain. Zhen Ci Yan Jiu 2009; 34: 376-82.
49.	D'Mello R, Marchand F, Pezet S, et al. Perturbing PSD-95 interactions with NR2B-subtype receptors attenuates spinal nociceptive plasticity and neuropathic pain. Mol Ther 2011; 19: 1780-92. DOI PMID
50.	Lin TB, Lai CY, Hsieh MC, et al. Neuropathic allodynia involves spinal neurexin-1β-dependent neuroligin-1/postsynaptic density-95/NR2B cascade in rats. Anesthesiology 2015; 123: 909-26.

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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

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