罗浮山风湿膏药通过抑制TLR4/TNF-α信号通路缓解小鼠神经病理性疼痛

doi:10.12122/j.issn.1673-4254.2025.11.01

南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (11): 2285-2296.doi: 10.12122/j.issn.1673-4254.2025.11.01

• • 下一篇

罗浮山风湿膏药通过抑制TLR4/TNF-α信号通路缓解小鼠神经病理性疼痛

傅玉芳¹(), 谭伟玲¹^,², 李小翠¹, 林荣钿³(), 刘叔文¹^,⁴^,⁵(), 叶玲¹^,⁵()

^1.南方医科大学，药学院，广东广州 510515
^2.南方医科大学，中医药学院，广东广州 510515
^3.广东罗浮山国药股份有限公司工程实验室（抗风湿中药），广东惠州 516100
^4.南方医科大学附属坪山医院药学部，广东深圳 518100
^5.广东省中西医结合防治情志病基础研究卓越中心，广东广州 510515

收稿日期:2025-08-03 接受日期:2025-09-30 出版日期:2025-11-20 发布日期:2025-12-03
通讯作者: 林荣钿,刘叔文,叶玲 E-mail:fyf2001021600@163.com;47415242@qq.com;liusw@smu.edu.cn;yeling@smu.edu.cn
作者简介:傅玉芳，在读硕士研究生，E-mail：fyf2001021600@163.com

LuoFuShan Rheumatism Plaster ameliorates neuropathic pain in mice by suppressing TLR4/TNF-α signaling

Yufang FU¹(), Weiling TAN¹^,², Xiaocui LI¹, Rongtian LIN³(), Shuwen LIU¹^,⁴^,⁵(), Ling YE¹^,⁵()

^1.School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
^2.School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China
^3.Guangdong Engineering Research Center for Anti-Rheumatic Traditional Chinese Medicine, R&D Center, Guangdong Luofushan Sinopharm Co. , Ltd. , Huizhou 516100, China
^4.Department of Pharmacy, Pingshan Hospital, Southern Medical University, Shenzhen 518100, China
^5.Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515, China

Received:2025-08-03 Accepted:2025-09-30 Online:2025-11-20 Published:2025-12-03
Contact: Rongtian LIN, Shuwen LIU, Ling YE E-mail:fyf2001021600@163.com;47415242@qq.com;liusw@smu.edu.cn;yeling@smu.edu.cn
Supported by:
Scientific Connotation of Efficacy of LuoFuShan Rheumatism Plaster Based on Clinical Orientation(K924319081);基于临床导向的罗浮山风湿膏功效科学内涵研究(K924319081);National Natural Science Foundation of China(82422077);国家自然科学基金(82422077);Natural Science Foundation of Guangdong Province(2024B1515020093);广东省自然科学基金(2024B1515020093)

摘要/Abstract

摘要：

目的探究罗浮山风湿膏药（LFS）对神经病理性疼痛（NP）的治疗效果与作用机制。方法构建坐骨神经慢性压迫性损伤（CCI）小鼠模型，分别以低、中、高剂量（2.2、4.4、8.8 cm²）的LFS连续干预14 d。通过检测机械刺激缩足反射阈值（MWT）和热刺激缩足反射潜伏期（PWL），血浆炎症因子IL-6、TNF-α水平，以及坐骨神经组织病理学分析评估其治疗效果；采用网络药理学与分子对接技术筛选LFS抗NP的关键靶点及通路；通过RT-qPCR和免疫组化验证相关靶点和通路；最后测定心脏、肝脏、肾脏脏器系数及功能损伤标志物评价安全性。结果与CCI模型组相比，LFS可剂量依赖性地升高MWT与PWL，降低血浆炎症因子IL-6、TNF-α水平，减轻坐骨神经炎症的损伤程度（P<0.05）。网络药理学分析显示，LFS含378种活性成分，可作用于279个NP相关基因，主要富集于TLR和TNF信号通路。分子对接结果表明，LFS关键成分槲皮素和熊果酸可与TLR4和TNF-α靶点稳定结合。与CCI 模型组相比，LFS 可剂量依赖性地下调脊髓组织中Tlr4 和Tnf-α的mRNA 表达水平，小鼠坐骨神经中TLR4和TNF-α蛋白的表达亦同步降低（P<0.05）。安全性评估显示，各剂量LFS组脏器系数及心肝肾损伤标志物与CCI组和假手术组差异无统计学意义（P>0.05）。结论 LFS通过抑制TLR4/TNF-α通路介导的神经炎症缓解NP，且具有良好的安全性。

关键词: 罗浮山风湿膏药, 神经病理性疼痛, TLR4/TNF-α通路, 安全性评价

Abstract:

Objective To explore the therapeutic effect of LuoFuShan Rheumatism Plaster (LFS) on neuropathic pain (NP) and its molecular mechanism. Methods Mouse models of sciatic nerve chronic constriction injury (CCI) were treated with low, medium, and high doses (2.2, 4.4, and 8.8 cm², respectively) of LFS by topical application for 14 consecutive days. The therapeutic effects were assessed by evaluating the mechanical withdrawal threshold (MWT), paw withdrawal latency (PWL), plasma IL-6 and TNF-α levels, and histopathology of the sciatic nerve. Network pharmacology and molecular docking were used to identify the key targets and signaling pathways. The key targets were verified by RT-qPCR and immunohistochemistry. The biosafety of LFS was evaluated by measuring the organ indices and damage indicators of the heart, liver, and kidneys. Results Compared with the CCI group, LFS dose-dependently increased MWT and PWL, reduced plasma IL-6 and TNF-α levels, and alleviated sciatic nerve inflammation in the mouse models. Network pharmacology identified 378 bioactive compounds targeting 279 NP-associated genes enriched in TLR and TNF signaling. Molecular docking showed that quercetin and ursolic acid in LFS could stably bind to TLR4 and TNF‑α. In the mouse models of sciatic nerve CCI, LFS significantly downregulated the mRNA expression levels of Tlr4 and Tnf-α in the spinal cord in a dose-dependent manner and lowered the protein expressions of TLR4 and TNF-α in the sciatic nerve. LFS treatment did not cause significant changes in the organ indices or damage indicators of the heart, liver and kidneys as compared with those in the CCI model group and sham-operated group. Conclusion LFS alleviates NP in mice by suppression of TLR4/TNF-α-mediated neuroinflammation with a good safety profile.

Key words: LuoFuShan Rheumatism Plaster, neuropathic pain, TLR4/TNF-α signaling, Safety evaluation

傅玉芳, 谭伟玲, 李小翠, 林荣钿, 刘叔文, 叶玲. 罗浮山风湿膏药通过抑制TLR4/TNF-α信号通路缓解小鼠神经病理性疼痛[J]. 南方医科大学学报, 2025, 45(11): 2285-2296.

Yufang FU, Weiling TAN, Xiaocui LI, Rongtian LIN, Shuwen LIU, Ling YE. LuoFuShan Rheumatism Plaster ameliorates neuropathic pain in mice by suppressing TLR4/TNF-α signaling[J]. Journal of Southern Medical University, 2025, 45(11): 2285-2296.

图/表 7

Fig.1 LFS ameliorates CCI-induced NP in mice. A: Schematic illustration of the experimental design. B: Timeline of measuring mechanical pain threshold and thermal pain threshold in mice. C, D: Results of mechanical withdrawal threshold test and paw withdrawal latency test (n=8). E, F: Levels of IL-6 and TNF-α in plasma (n=8). G: HE staining of the sciatic nerve and histological scores (Original magnification: ×100, n=3). LFSL: Low-dose (2.2 cm2/back) LFS group; LFSM: Medium-dose (4.4 cm2/back) LFS group; LFSH: High-dose (8.8 cm2/back) group. Data are presented as Mean±SE. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

Tab.1 Key chemical components of LFS in treating NP

Name of Chinese medicine	Quantity of active ingredients
Angelica sinensis	67
Zanthoxylum nitidum	22
Drynaria fortunei	20
Carthamus tinctorius	18
Rubia cordifolia	17
Litsea cubeba	17
Saposhnikovia divaricata	15
Leonurus japonicus	14
Ephedra sinica	11
Datura metel	10
Stephania tetrandra	9
Achyranthes bidentata	8
Notopterygium incisum	7
Dictamnus dasycarpus	6
Aconitum kusnezoffii	6
oxicodendron vernicifluum	6
Angelica pubescens	5
Entada phaseoloides	5
Viscum coloratum	5
Schizonepeta tenuifolia	5
Strophanthus divaricatus	5
Eleutherococcus gracilistylus	5
Abrus cantoniensis	4
Dipsacus asperoides	4
Panax notoginseng	3
Aconitum carmichaelii	2
Erycibe obtusifolia	2
Bungarus multicinctus	2
Laggera alata	2
Chaenomeles speciosa	2
Schefflera arboricola	2
Pseudolarix amabilis	2
Semiliquidambar cathayensis	1
Ricinus communis	1
Dioscorea hypoglauca	1
Tinospora sinensis	1
Adenosma glutinosum	1
Clematis chinensis	1
Ardisia crenata	1
Cynanchum paniculatum	1
Pinus tabuliformis	1
Component shared by multiple drugs	61
Total	378

Fig. 2 Network pharmacology reveals multi-target mechanisms of LFS against NP. A: Diagram of Venn analysis of the intersection targets between LFS and NP. B: PPI network of the targets regulated by LFS. C, D: PPI network of NP and LFS intersection targets and key targets. E, F: GO functional enrichment analysis and KEGG pathway analysis of LFS in the treatment of NP.

Tab.2 Top 10 active ingredients in LFS and the topological parameters

ID	Name	Degree	DL	Source
MOL000098	Quercetin	26	0.28	multiDrug
MOL000511	Ursolic acid	17	0.75	multiDrug
MOL000006	Luteolin	12	0.25	multiDrug
MOL011865	Rosmarinic	9	0.35	multiDrug
MOL000422	Kaempferol	9	0.24	multiDrug
MOL000008	Apigenin	9	0.21	multiDrug
MOL002714	Baicalein	8	0.21	multiDrug
MOL001439	Arachidonic acid	8	0.20	multiDrug
MOL000472	Emodin	8	0.24	jigucao
MOL013179	Fisetin	7	0.24	qishugen

Fig. 3 Molecular docking validates TLR4/TNF‑α interactions with LFS components. A, B: Docking results of TLR4 with quercetin and ursolic acid. C, D: Docking results of TNF-α with quercetin and ursolic acid.

Fig.4 LFS suppress TLR4/TNF-α signaling in the spinal cord and sciatic nerve. A, B: mRNA expression of Tlr4 and Tnf-α in the spinal cord (n=5). C, D: Protein expression of TLR4 and TNF‑α in the sciatic nerve of mice by immunohistochemical staining (n=3). Data are presented as Mean±SE. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

Fig. 5 Biosafety of LFS in the treatment of NP. A-C: Organ index of the heart, liver, and kidneys (n=8). D-I: Plasma levels of LDH, CK, AST, ALT, BUN and Scr in mice (n=8). Data are presented as Mean±SE.

参考文献 42

[1]	Attal N, Bouhassira D, Colvin L. Advances and challenges in neuropathic pain: a narrative review and future directions [J]. Br J Anaesth, 2023, 131(1): 79-92. doi：10.1016/j.bja.2023.04.021
[2]	Cohen SP, Mao J. Neuropathic pain: mechanisms and their clinical implications [J]. BMJ, 2014, 348: f7656. doi：10.1136/bmj.f7656
[3]	Ahmadi R, Kuner R, Weidner N, et al. The Diagnosis and treatment of neuropathic pain [J]. Dtsch Arztebl Int, 2024, 121(25): 825-32.
[4]	Ji RR, Chamessian A, Zhang YQ. Pain regulation by non-neuronal cells and inflammation [J]. Science, 2016, 354(6312): 572-7. doi：10.1126/science.aaf8924
[5]	Bannister K, Sachau J, Baron R, et al. Neuropathic pain: mechanism-based therapeutics [J]. Annu Rev Pharmacol Toxicol, 2020, 60: 257-74. doi：10.1146/annurev-pharmtox-010818-021524
[6]	Si W, Li X, Jing B, et al. Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF-κB pathway to alleviate neuropathic pain [J]. Phytother Res, 2024, 38(1): 265-79. doi：10.1002/ptr.8039
[7]	Qindeel M, Ullah MH, Fakhar UD, et al. Recent trends, challenges and future outlook of transdermal drug delivery systems for rheumatoid arthritis therapy [J]. J Control Release, 2020, 327: 595-615. doi：10.1016/j.jconrel.2020.09.016
[8]	Wu TF, Deng J, Wang X, et al. Textual research on Bungarus Parvus [J]. Chin J Chin Mater Med, 2023, 48(22): 6234-48.
[9]	Chawla R, Kumar S, Sharma A. The genus Clematis (Ranunculaceae): chemical and pharmacological perspectives [J]. J Ethnopharmacol, 2012, 143(1): 116-50. doi：10.1016/j.jep.2012.06.014
[10]	Wang LL, Kang ML, Liu CW, et al. Panax notoginseng saponins activate nuclear factor erythroid 2-related factor 2 to inhibit ferroptosis and attenuate inflammatory injury in cerebral ischemia-reperfusion [J]. Am J Chin Med, 2024, 52(3): 821-39. doi：10.1142/s0192415x24500332
[11]	Chen Y, Duan JA, Qian D, et al. Assessment and comparison of immunoregulatory activity of four hydrosoluble fractions of Angelica sinensis in vitro on the peritoneal macrophages in ICR mice [J]. Int Immunopharmacol, 2010, 10(4): 422-30. doi：10.1016/j.intimp.2010.01.004
[12]	Zhao WH. The clinical effect observation of luofushan rheumatism plaster intreatment of sciatica [J]. Chin J Clin Rational Drug Use, 2018, 11(19): 30-31.
[13]	HANBALI O A AL, KHAN HMS, Sarfraz M, et al. Transdermal patches: design and current approaches to painless drug delivery [J]. Acta Pharm, 2019, 69(2): 197-215. doi：10.2478/acph-2019-0016
[14]	Borgonetti V, Governa P, Biagi M, et al. Zingiber officinale Roscoe rhizome extract alleviates neuropathic pain by inhibiting neuroinflammation in mice [J]. Phytomedicine, 2020, 78: 153307. doi：10.1016/j.phymed.2020.153307
[15]	Feng X, Ju P, Chen Y, et al. Analgesic alkaloids from Urticae Fissae Herba [J]. Chin Herb Med, 2022, 14(1): 125-9. doi：10.1016/j.chmed.2021.09.008
[16]	Ayik B, Ortadeveci A, Bakilan F, et al. Comparison of the effects of perineural and intraperitoneal ozone therapy on nerve healing in an experimental sciatic nerve injury model [J]. Medicina (Kaunas), 2024, 60(12): 2097. doi：10.3390/medicina60122097
[17]	Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets [J]. Nat Commun, 2019, 10(1): 1523. doi：10.1038/s41467-019-09234-6
[18]	Wang ZY, Han QQ, Deng MY, et al. Lemairamin, isolated from the Zanthoxylum plants, alleviates pain hypersensitivity via spinal α7 nicotinic acetylcholine receptors [J]. Biochem Biophys Res Commun, 2020, 525(4): 1087-94. doi：10.1016/j.bbrc.2020.03.023
[19]	Kumar N, Goel R, Ansari MN, et al. Formulation of phytosomes containing Rubia cordifolia extract for neuropathic pain: in vitro and in vivo evaluation [J]. ACS Omega, 2024, 9(23): 25381-9. doi：10.1021/acsomega.4c03774
[20]	Li L, Sun L, Qiu Y, et al. Protective effect of stachydrine against cerebral ischemia-reperfusion injury by reducing inflammation and apoptosis through P65 and JAK2/STAT3 signaling pathway [J]. Front Pharmacol, 2020, 11: 64. doi：10.3389/fphar.2020.00064
[21]	Tanimura Y, Yoshida M, Ishiuchi K, et al. Neoline is the active ingredient of processed aconite root against murine peripheral neuropathic pain model, and its pharmacokinetics in rats [J]. J Ethnopharmacol, 2019, 241: 111859. doi：10.1016/j.jep.2019.111859
[22]	Liu M, Qiang QH, Ling Q, et al. Effects of Danggui Sini decoction on neuropathic pain: experimental studies and clinical pharmacological significance of inhibiting glial activation and proinflammatory cytokines in the spinal cord [J]. Int J Clin Pharmacol Ther, 2017, 55(5): 453-64. doi：10.5414/cp202613
[23]	Shoaib RM, Ahsan MZ, Akhtar U, et al. Ginsenoside Rb1, a principal effective ingredient of Panax notoginseng, produces pain antihypersensitivity by spinal microglial dynorphin A expression [J]. Neurosci Res, 2023, 188: 75-87. doi：10.1016/j.neures.2022.11.003
[24]	Mustafa S, Evans S, Barry B, et al. Toll-Like Receptor 4 in pain: bridging molecules-to-cells-to-systems [J]. Handb Exp Pharmacol, 2022, 276: 239-73. doi：10.1007/164_2022_587
[25]	Mengge S, Quan J, Juan J, et al. A multicenter randomized double-blind controlled clinical study of Luofushan rheumatism Plaster in the treatment of rheumatoid arthritis carpal arthritis [J]. J Beijing Univ Chin Med, 2023, 46(10): 1431-42.
[26]	Tange FY, Nutile-Mcmenemy N, Deleo JA. The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy [J]. Proc Natl Acad Sci U S A, 2005, 102(16): 5856-61. doi：10.1073/pnas.0501634102
[27]	Svensson CI, Sshäfers M, Jones TL, et al. Spinal blockade of TNF blocks spinal nerve ligation-induced increases in spinal P-p38 [J]. Neurosci Lett, 2005, 379(3): 209-13. doi：10.1016/j.neulet.2004.12.064
[28]	Liu C, Liu DQ, Tian YK, et al. The emerging role of quercetin in the treatment of chronic pain [J]. Curr Neuropharmacol, 2022, 20(12): 2346-53. doi：10.2174/1570159x20666220812122437
[29]	Bhat RA, Lingaraju MC, Pathak NN, et al. Effect of ursolic acid in attenuating chronic constriction injury-induced neuropathic pain in rats [J]. Fundam Clin Pharmacol, 2016, 30(6): 517-28. doi：10.1111/fcp.12223
[30]	Wu X, Liu A, Lv X, et al. Network pharmacology and experimental study of Angelica sinensis and Astragalus membranaceus capsules in treating heart failure [J]. Heliyon, 2024, 10(20): e38851. doi：10.1016/j.heliyon.2024.e38851
[31]	Wang W, Yang C, Xia J, et al. Novel insights into the role of quercetin and kaempferol from Carthamus tinctorius L. in the management of nonalcoholic fatty liver disease via NR1H4-mediated pathways [J]. Int Immunopharmacol, 2024, 143(Pt 1): 113035. doi：10.1016/j.intimp.2024.113035
[32]	Han J, Hou J, Liu Y, et al. Using network pharmacology to explore the mechanism of Panax notoginseng in the treatment of myocardial fibrosis [J]. J Diabetes Res, 2022, 2022: 8895950. doi：10.1155/2022/8895950
[33]	Zhang L, Feng Y, Ding A. The research on the chemical components of Schizonepeta tenuifolia Briq [J]. Chin Tradit Herb Drugs, 2001, 24(3): 183-4.
[34]	Hou W, Wei B, Liu HS. The Protective effect of Panax notoginseng mixture on hepatic ischemia/reperfusion injury in mice via regulating NR3C2, SRC, and GAPDH [J]. Front Pharmacol, 2021, 12: 756259. doi：10.3389/fphar.2021.756259
[35]	Bhat RA, Lingaraju MC, Pathak NN, et al. Effect of ursolic acid in attenuating chronic constriction injury-induced neuropathic pain in rats. Fundam Clin Pharmacol. 2016, 30(6):517-28. doi：10.1111/fcp.12223
[36]	Muto N, Matsuoka Y, Arakawa K, al et, Quercetin attenuates neuropathic pain in rats with spared nerve injury [J]. Acta Med Okayama, 2018,72(5): 457-65.
[37]	Okselni T, Septama AW, Juliadmi D, et al. Quercetin as a therapeutic agent for skin problems: a systematic review and meta-analysis on antioxidant effects, oxidative stress, inflammation, wound healing, hyperpigmentation, aging, and skin cancer [J]. Naunyn-Schmiedeberg's Arch Pharmacol, 2025, 398: 5011-55. doi：10.1007/s00210-024-03722-3
[38]	Jamal M, Imam SS, Aqil M, et al. Transdermal potential and anti-arthritic efficacy of ursolic acid from niosomal gel systems [J]. Int Immunopharmacol, 2015, 29(2): 361-9. doi：10.1016/j.intimp.2015.10.029
[39]	Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited [J]. FASEB J, 2008, 22(3): 659-61. doi：10.1096/fj.07-9574lsf
[40]	Gopalsamy B, Sambasevam Y, Zulazmi NA, et al. Experimental characterization of the chronic constriction injury-induced neuropathic pain model in mice [J]. Neurochem Res, 2019, 44(9): 2123-38. doi：10.1007/s11064-019-02850-0
[41]	Starowicz K, Przewlocka B. Modulation of neuropathic-pain-related behaviour by the spinal endocannabinoid/endovanilloid system [J]. Philos Trans R Soc Lond B Biol Sci, 2012, 367(1607): 3286-99. doi：10.1098/rstb.2011.0392
[42]	Colleoni M, Sacerdote P. Murine models of human neuropathic pain [J]. Biochim Biophys Acta, 2010, 1802(10): 924-33. doi：10.1016/j.bbadis.2009.10.012

罗浮山风湿膏药通过抑制TLR4/TNF-α信号通路缓解小鼠神经病理性疼痛

LuoFuShan Rheumatism Plaster ameliorates neuropathic pain in mice by suppressing TLR4/TNF-α signaling

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 7

参考文献 42

相关文章 9

编辑推荐

Metrics

本文评价

[1]	苏炳森, 操龙斌, 郑介婷, 张琳, 张子康, 邱峰. 健康妇女生殖道内格氏乳杆菌的分离鉴定与安全性评价[J]. 南方医科大学学报, 2021, 41(12): 1809-1815.
[2]	闫芳, 陈东泰, 谢敬敦, 曾维安, 李强. 七叶皂苷通过诱导自噬缓解化疗引起的外周神经病理性疼痛[J]. 南方医科大学学报, 2020, 40(11): 1634-1638.
[3]	王琛，陈鹏，林东升，陈弋，吴智兵，林兴栋. 不同结扎材料对慢性压迫性损伤模型胶质细胞活化的影响[J]. 南方医科大学学报, 2020, 40(08): 1207-1212.
[4]	欧阳碧函，唐朝辉，侯新冉，陈旦，郭曲练，翁莹琪. 曲古菌素A抑制神经病理性痛大鼠脊髓HDAC4上调并逆转差异表达的miRNAs[J]. 南方医科大学学报, 2019, 39(12): 1421-1426.
[5]	盛恒炜，磨凯. ZHX2在调控背根神经节m阿片受体表达致神经病理性痛中的作用[J]. 南方医科大学学报, 2019, 39(08): 917-.
[6]	李双凤，欧阳碧山，赵鑫，王亚平. 右美托咪定对奥沙利铂致神经性疼痛的镇痛作用及机制[J]. 南方医科大学学报, 2018, 38(07): 836-.
[7]	徐华丽，徐世元，磨凯. 蛋白精氨酸甲基化酶在小鼠外周神经损伤后背根神经节中的转录表达[J]. 南方医科大学学报, 2017, 37(12): 1620-.
[8]	游霁月，高进，陈萍，孙琳，杨晓秋. 碱性成纤维细胞生长因子在大鼠坐骨神经分支选择性损伤后的动态变化[J]. 南方医科大学学报, 2013, 33(04): 563-.
[9]	周国斌，李红英，吉锦泉，于卫，马薇涛. COX抑制剂对神经病理性疼痛大鼠镇痛效果及机制[J]. 南方医科大学学报, 2011, 31(10): 1764-.