来源：风湿病与关节炎,2019,8（3）:33-37.

补骨颗粒治疗骨关节炎慢性疼痛的机制研究（临床研究）

余光书¹，乐立盛²，卓　杰²，林焱斌¹，熊国胜¹

　　【摘　要】目的：通过观察补骨颗粒对骨关节炎患者慢性疼痛及缓激肽（BK）、降钙素基因相关肽（CGRP）、转化受体电位阳离子通道亚家族A成员1（TRPA1）的影响，探讨补肾活血中药对骨关节炎慢性疼痛的影响机制，为临床防治骨关节炎慢性疼痛提供依据。方法：选取40例膝关节疼痛的骨科门诊患者，按照美国风湿病学会（ACR）标准诊断为单侧或双侧膝骨关节炎，中医诊断符合《中医病证诊断疗效标准》中骨痹（肾虚血瘀型），患者每日严格按时口服补骨颗粒，并在口服中药第0，7，14天时采用视觉模拟评分法（VAS）评估患者膝关节静息痛，同时抽取3～4 mL静脉血行TRPA1、CGRP及BK检测，所有检测值记录于预先设置好的表格内，使用SPSS 20.0软件进行统计分析。结果：共有32例患者按照试验方案服药，所纳入患者在口服中药前的静息痛VAS评分为54.38分，治疗7 d（44.69分）及14 d（32.81分）后患者的平均静息痛均明显缓解（F = 44.323，P = 0.000）；治疗前患者BK值为7.72 ng·mL^-1，治疗7 d后（6.61 ng·mL^-1）与14 d后（5.98 ng·mL^-1）均明显降低（F = 30.025，P = 0.000）；治疗后CGRP下降，但多重比较发现，治疗前与治疗7，14 d比较，差异有统计学意义（P = 0.015，P = 0.002），而治疗7 d与14 d差异无统计学意义（P = 0.469）；治疗后TRPA1值下降，多重比较发现，治疗前与治疗7 d差异无统计学意义（P = 0.243），治疗前与治疗14 d差异有统计学意义（P = 0.000），治疗7 d与14 d差异有统计学意义（P = 0.000）。结论：补骨颗粒能够有效缓解骨关节炎患者慢性疼痛，这可能通过抑制TRPA1、CGRP及BK的表达或分泌，从而起到抑制外周感受器敏化及中枢敏化的作用。

　　【关键词】　骨关节炎，膝；补骨颗粒；慢性疼痛；TRPA1；中枢敏化；临床研究

On the Mechanism of Bugu Keli（补骨颗粒）in Treating Chronic Pain of Osteoarthritis

YU Guang-shu,LE Li-sheng,ZHUO Jie,LIN Yan-bin,XIONG Guo-sheng

　　【ABSTRACT】Objective:By observing the effects of Bugu Keli（补骨颗粒）on chronic pain,BK,CGRP and TRPA1 in patients with osteoarthritis,to explore the its mechanism,so as to provide evidence for clinical prevention and treatment.Methods:Forty patients with knee joint pain were recruited and diagnosed as unilateral or bilateral knee osteoarthritis according to the criteria of American Rheumatology Society.Then they were diagnosed as bone bi（of kidney deficiency and blood stasis type）in terms of The Criteria of Diagnosis and Curative Effect of Osteoarthritis.The patients were given Chinese medicine for tonifying kidney and activating blood circulation strictly and on time.Before taking medicine,the seventh day and the fourteenth day after that,VAS was used to assess the rest pain of knee joint.At the same time,3～4 mL venous blood samples were taken for TRPA1,CGRP and BK detection.All the detection values were recorded in the pre-set tables and statistically analyzed with software SPSS 20.0.Results:A total of 32 patients were treated with Chinese medicine.The VAS score of rest pain before oral administration was 54.38.The average resting pain of patients after 7 days（44.69 points）and 14 days（32.81 points）was significantly relieved（F = 44.323,P = 0.000）.The BK value of patients before treatment was 7.72 ng·mL^-1,and after 7 days（6.61 ng·mL^-1）and 14 days（5.98 ng·mL^-1）decreased significantly（F = 30.025,P = 0.000）.CGRP decreased after treatment,but multiple comparisons showed that there were significant differences between pre-treatment and 7 days’ treatment（P = 0.015）,between pre-treatment and 14 days’ treatment（P = 0.002）,while there was no significant difference between 7 days’ and 14 days’ treatments（P = 0.469）.TRPA1 decreased after treatment,and multiple comparisons showed no difference between pre-treatment and 7 days’ treatment（P = 0.243）,significant statistical significance between pre-treatment and 14 day’ of treatment（P = 0.000）,between 7 days’ and 14 days’ treatments（P = 0.000）.Conclusion:Bugu Keli can effectively relieve chronic pain in patients with osteoarthritis,which may inhibit peripheral sensitization and central sensitization by inhibiting the expression or secretion of TRPA1,CGRP and BK.

　　【Keywords】 osteoarthritis,knee;Bugu Keli（补骨颗粒）;chronic pain;TRPA1;central sensitization;clinical research