自拟癌痛止痛贴膏联合盐酸羟考酮治疗难治性癌性疼痛的效果观察

杜莉; 许远; 张炼; 徐桂花; 王桂芬; 刘震杰

doi:10.16766/j.cnki.issn.1674-4152.002531

自拟癌痛止痛贴膏联合盐酸羟考酮治疗难治性癌性疼痛的效果观察

doi: 10.16766/j.cnki.issn.1674-4152.002531

杜莉^1, ,,
许远¹,
张炼¹,
徐桂花¹,
王桂芬¹,
刘震杰²

1.
衢州市中医医院肿瘤内科，浙江衢州 324002
2.
浙江大学医学院附属第二医院血管外科，浙江杭州 310000

基金项目:

国家自然科学基金项目 81970398

详细信息

通讯作者:
杜莉, E-mail: DULI116@126.com

中图分类号: R730.5 R244.9
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- 被引次数: 0
出版历程
- 收稿日期: 2021-10-29
- 网络出版日期: 2022-09-23

Effect of self-designed cancer pain analgesic plaster combined with oxycodone hydrochloride on refractory cancer pain

1.
Internal Medicine-Oncology, Quzhou Hospital of Traditional Chinese Medicine, Quzhou, Zhejiang 324002, China

摘要

摘要: 目的观察自拟外敷癌痛止痛贴膏联合盐酸羟考酮治疗难治性癌性疼痛的效果。方法选择2019年1月—2020年6月衢州市中医医院收治的102例难治性癌性疼痛患者，按照随机数字表法分为对照组和观察组，各51例。对照组给予盐酸羟考酮缓释片，观察组在对照组基础上给予自拟外敷癌痛止痛贴膏治疗，对比疼痛治疗效果、数字疼痛评分(NRS)、羟考酮应用剂量、爆发痛次数、疼痛缓解平均起始时间、Karnofsky功能状态(KPS)评分、焦虑自评量表(SAS)评分、每日睡眠时间，监测血清中相关致痛介质、免疫调节因子水平。结果观察组的总有效率为93.62%(44/47)，显著高于对照组的77.78%(35/45，P＜0.05)；治疗1 d、治疗1周同一时间点比较，观察组的疼痛NRS评分显著低于对照组(均P＜0.05)；治疗后，与对照组相比，观察组患者的羟考酮应用剂量减少，爆发痛次数更少，疼痛缓解平均起始时间显著缩短(均P＜0.05)；观察组患者的生活质量KPS评分显著升高，焦虑SAS评分更低，睡眠时间显著增加，血清中致痛介质P物质(SP)、前列腺素E₂(PGE₂)明显降低，β内啡肽(β-EP)含量明显升高(均P＜0.05)；治疗1 d、治疗1周同一时间点比较，观察组的血清中IL-2含量明显高于对照组(均P＜0.05)；2组患者的不良反应发生率比较，差异无统计学意义(P＞0.05)。结论自拟外敷癌痛止痛贴膏联合盐酸羟考酮治疗难治性癌性疼痛安全有效，其机制可能与调节血清中SP、PGE₂、β-EP、IL-2含量以镇痛、增强免疫功能有关。
- 难治性癌性疼痛 /
- 自拟外敷癌痛止痛贴膏 /
- 盐酸羟考酮
Abstract: Objective To observe the effect of self-designed external application of cancer pain analgesic plaster combined with oxycodone hydrochloride in the treatment of refractory cancer pain. Methods A total of 102 patients with refractory cancer pain admitted to Quzhou Hospital of Traditional Chinese Medicine from January 2019 to June 2020 were selected and divided into the control group and observation group, with 51 cases in each group. The control group was given oxycodone hydrochloride sustained-release tablets, and the observation group was treated with self-designed external application of cancer pain analgesic plaster on the basis of the control group. The clinical pain treatment effect, digital pain score (NRS), dosage of oxycodone, frequency of pain outbreak, average starting time of pain relief, Karnofsky functional status (KPS) score, self-rating anxiety scale (SAS) score and daily sleep time changes were compared. The serum levels of pain-causing mediators and immunoregulatory factors were monitored. Results The effective rate of observation group was 93.62%(44/47), which was significantly higher than that of the control group (77.78%, 35/45, P < 0.05). The NRS score of the observation group was significantly lower than that of the control group at 1 day and 1 week after treatment (all P < 0.05). After treatment, compared with the control group, the dose of oxycodone in the observation group was reduced, the number of pain bursts was less and the average time to start pain relief was significantly shortened (all P < 0.05). In the observation group, the KPS score of quality of life significantly increased, the anxiety SAS score was lower, sleep time was significantly increased, the serum pain transmitters SP and PGE₂ were significantly decreased and β-EP content significantly increased (all P < 0.05). The IL-2 level in the observation group was significantly higher than that in the control group (all P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion Self-designed external application of cancer pain analgesia plaster combined with oxycodone hydrochloride in the treatment of refractory cancer pain is safe and effective. Its mechanism may be related to the regulation of serum substance P(SP), prostaglandin E₂(PGE₂), β-EP and IL-2 levels to relieve pain and enhance immune function.
- Refractory cancer pain /
- Self-designed external application of cancer pain analgesic plaster /
- Oxycodone hydrochloride

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表 1 2组难治性癌性疼痛患者治疗疼痛的总有效率比较

Table 1. Comparison of the total effective rate of pain treatment between two groups of patients with refractory cancer pain

组别	例数	完全缓解(例)	部分缓解(例)	轻度缓解(例)	无效(例)	总有效率(%)
观察组	47	11	24	9	3	93.62(44/47)
对照组	45	6	17	12	10	77.78(35/45)
注：2组总有效率比较，χ²=4.753，P=0.029。

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表 2 2组难治性癌性疼痛患者治疗前后疼痛NRS评分比较(x±s，分)

Table 2. Comparison of pain NRS scores between the two groups before and after treatment (x±s, points)

组别	例数	治疗前	治疗1 d	治疗1周	F值	P值
观察组	47	6.23±0.34	2.68±0.25^a	1.73±0.11^ab	27.054	＜0.001
对照组	45	6.19±0.35	4.10±0.37^a	3.28±0.29^ab	11.390	＜0.001
t值		-0.556	-21.653	-34.171
P值		0.580	＜0.001	＜0.001
注：与同组治疗前比较，^aP＜0.05；与同组治疗1 d比较，^bP＜0.05。

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表 3 2组难治性癌性疼痛患者羟考酮应用剂量、爆发痛次数、疼痛缓解平均起始时间比较(x±s)

Table 3. Comparison of oxycodone dose, frequency of pain outbreak and average onset time of pain relief between the two groups (x±s)

组别	例数	羟考酮应用剂量(mg/周)	爆发痛次数(次/周)	疼痛缓解平均起始时间(min)
观察组	47	58.12±3.59	2.11±0.09	26.15±5.78
对照组	45	64.47±5.29	3.75±0.74	52.36±9.07
t值		-6.763	-15.081	-16.603
P值		＜0.001	＜0.001	＜0.001

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表 4 2组难治性癌性疼痛患者生活质量KPS评分、焦虑SAS评分、睡眠时间比较(x±s)

Table 4. Comparison of KPS score of quality of life, SAS score of anxiety and sleep time between the two groups (x±s)

组别	例数	KPS评分(分)		焦虑SAS评分(分)		睡眠时间(h/d)
组别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
观察组	47	56.20±2.74	77.12±3.30	71.28±5.34	42.41±4.28	5.83±0.49	7.24±1.32
对照组	45	56.23±2.68	63.29±2.86	70.73±5.40	52.50±7.08	5.78±0.47	6.03±0.77
t值		-0.053	21.441	0.491	-8.313	0.499	5.340
P值		0.958	＜0.001	0.625	＜0.001	0.619	＜0.001

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表 5 2组难治性癌性疼痛患者血清中疼痛递质水平比较(x±s)

Table 5. Comparison of serum levels of pain transmitters between the two groups (x±s)

组别	例数	SP(ng/mL)		PGE₂(ng/L)		β-EP(ng/L)
组别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
观察组	47	21.75±3.56	7.20±0.05	210.52±15.75	23.64±4.40	153.34±25.19	252.70±31.58
对照组	45	21.63±3.77	16.20±1.42	211.93±14.93	75.50±7.85	155.02±25.33	210.57±27.87
t值		0.157	-22.276	-0.440	-39.305	-0.319	6.773
P值		0.876	＜0.001	0.661	＜0.001	0.751	＜0.001

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表 6 2组难治性癌性疼痛患者治疗前后免疫调节相关因子IL-2含量比较(x±s, pg/mL)

Table 6. Comparison of IL-2 content of immunomodulatory factor before and after treatment between the two groups (x±s, pg/mL)

组别	例数	治疗前	治疗1 d	治疗1周	F值	P值
观察组	47	28.78±4.54	47.67±6.21^a	62.27±7.80^ab	34.570	＜0.001
对照组	45	28.65±4.73	36.17±4.87^a	43.42±5.93^ab	21.048	＜0.001
t值		0.135	9.855	13.006
P值		0.893	＜0.001	＜0.001
注：与同组治疗前比较，^aP＜0.05；与同组治疗1 d比较，^bP＜0.05。

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表 7 2组难治性癌性疼痛患者不良反应发生情况比较

Table 7. Comparison of adverse reactions between the two groups of patients with refractory cancer pain

组别	例数	恶心(例)	嗜睡(例)	便秘(例)	纳少(例)	不良反应发生率(%)
观察组	47	1	2	5	2	21.28(10/47)
对照组	45	3	5	6	3	37.78(17/45)
注：2组患者不良反应发生率比较，χ²=3.019，P=0.082。

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参考文献(22)

[1]	HUNG G, LIU G, ZHOU Z G, et al. Successful treatment of refractory cancer pain and depression with continuous intrathecal administration of dexmedetomidine and morphine: A case report[J]. Pain Ther, 2020, 9(2): 797-804. doi: 10.1007/s40122-020-00183-3
[2]	CHEUNG K W A, CHAN P C, LO S H. The use of ketamine in the management of refractory cancer pain in a palliative care unit[J]. Ann Palliat Med, 2020, 9(6): 4478-4489. doi: 10.21037/apm.2019.09.09
[3]	RABIA S A, DHARMA N, JESSICA G, et al. A multi-centered case series highlighting the clinical use and dosing of lidocaine and mexiletine for refractory cancer pain[J]. Palliat Care, 2020, 34(2): 90-98.
[4]	王凯文, 蒯仂, 金燊懿, 等. 基于中医传承辅助平台的癌痛外敷方用药规律分析[J]. 中国中医基础医学杂志, 2020, 26(2): 254-257. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYJC202002033.htm WANG K W, QUAI L, JIN Q Y, et al. External application of cancer pain based on traditional Chinese medicine inheritance auxiliary platform[J]. Chinese journal of basic medicine of traditional Chinese medicine, 2020, 26(2): 254-257. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYJC202002033.htm
[5]	胡陵静, 郭婷婷, 叶海英, 等. 中医外治四联梯级疗法治疗癌性疼痛的探讨与应用[J]. 中国中医急症, 2021, 30(1): 105-108. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYJZ202101029.htm HU L J, GUO T T, YE H Y, et al. Discussion and application of quadruple cascade therapy in the treatment of cancer pain[J]. Chinese Medical emergenc, 2021, 30(1): 105-108. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYJZ202101029.htm
[6]	王昆, 金毅. 难治性癌痛专家共识(2017年版)[J]. 中国肿瘤临床, 2017, 44(16): 787-793. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZL201716001.htm WANG K, JIN Y. Expert Consensus on Refractory Cancer Pain (2017 edition)[J]. Chinese Journal of Clinical Oncology, 2017, 44(16): 787-793. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZL201716001.htm
[7]	谭冠先, 罗健, 屠伟峰. 癌痛治疗学[M]. 郑州: 河南科学技术出版社, 2019: 201-202. TAN G X, LUO J, TU W F. Cancer pain therapy[M]. Zhengzhou: Henan Science and Technology Press, 2019: 201-202.
[8]	ZHOU N B, WANG K G, FU Z J. Effect of morphine and a low dose of ketamine on the T cells of patients with refractory cancer pain in vitro[J]. Oncol lett, 2019, 18(4): 4230-4236.
[9]	ASHWIN V, ADITYA V, KENNETH R, et al. Minimally invasive cordotomy for refractory cancer pain: A randomized controlled trial[J]. Oncologist, 2019, 24(7): 590-596. doi: 10.1634/theoncologist.2018-0570
[10]	陈雨, 林青, 刘传波, 等. 癌性疼痛的中医治疗进展[J]. 医学综述, 2020, 26(20): 4112-4116. doi: 10.3969/j.issn.1006-2084.2020.20.030 CHEN Y, LIN Q, LIU C B, et al. Progress of traditional Chinese medicine in the treatment of cancer pain[J]. Medical review, 2020, 26(20): 4112-4116. doi: 10.3969/j.issn.1006-2084.2020.20.030
[11]	彭筱娴, 张培彤. 从叶天士络病理论探析癌性疼痛治法[J]. 中医学报, 2021, 36(3): 465-468. https://www.cnki.com.cn/Article/CJFDTOTAL-HNZK202103004.htm PENG X X, ZHANG P T. Research on the treatment of cancer pain from the theory of ye tianshilu disease[J]. Journal of traditional Chinese medicine, 2021, 36(3): 465-468. https://www.cnki.com.cn/Article/CJFDTOTAL-HNZK202103004.htm
[12]	蔡昀方, 刘春喜, 刘信毅, 等. 奥施康定联合氟比洛芬酯治疗中重度肿瘤骨转移患者疼痛的临床观察[J]. 中华全科医学, 2020, 18(7): 1122-1124. doi: 10.16766/j.cnki.issn.1674-4152.001444 CAI Y F, LIU C X, LIU X Y, et al. Clinical observation of oxyContin combined with flurbiprofen axetil in the treatment of pain in patients with moderate to severe tumor bone metastases[J]. Chinese Journal of General Practice, 2020, 18(7): 1122-1124. doi: 10.16766/j.cnki.issn.1674-4152.001444
[13]	齐宏亮, 曲迎春, 尹诗航. 盐酸羟考酮缓释片在老年癌痛患者中的应用效果分析[J]. 癌症进展, 2021, 19(3): 283-285. https://www.cnki.com.cn/Article/CJFDTOTAL-AZJZ202103018.htm QI H L, QU Y C, YIN S H. Effect of oxycodone hydrochloride sustained-release tablets in elderly patients with cancer pai[J]. Cancer Progression, 2021, 19(3): 283-285. https://www.cnki.com.cn/Article/CJFDTOTAL-AZJZ202103018.htm
[14]	RAGHU S T, RAGHAVENDRA R, ARIF A, et al. Indian Society for Study of Pain, Cancer Pain Special Interest Group guidelines on pharmacological management of cancer pain (part Ⅱ)[J]. Indian J Palliat Care, 2020, 26(2): 180-190. doi: 10.4103/0973-1075.285693
[15]	WANG K Y, GU Y, LIAO Y H, et al. PD-1 blockade inhibits osteoclast formation and murine bone cancer pain[J]. J Clin Invest, 2020, 130(7): 3603-3620. doi: 10.1172/JCI133334
[16]	YOGESH R, GANGA S, BHAWNA W. Role of intravenous ketamine as adjuvant to opioids in refractory cancer pain: Case report[J]. Nepal J Cancer, 2019, 3(1): 49-53. doi: 10.3126/njc.v3i1.25916
[17]	王淑美, 王维, 李配富, 等. 郁消散外敷对癌痛患者β内啡肽和P物质的影响[J]. 中国肿瘤临床与康复, 2018, 25(5): 560-562. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZK201805013.htm WANG S M, WANG W, LI P F, et al. Effect of external application of stagnation dissipation on β-endorphin and substance P in patients with cancer pain[J]. Oncology Clinic and Rehabilitation in China, 2018, 25(5): 560-562. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZK201805013.htm
[18]	CHONG D, SHAO L, YANG Y, et al. Correlations of cancer pain degree with levels of β-EP, CGRP and PGE₂ and the effects of oxycontin on them[J]. J BUON, 2018, 23(5): 1552-1557.
[19]	吴盛, 宋益青, 张建军, 等. 补肾祛瘀针刺疗法加穴位注射治疗肺癌骨转移重度癌痛对5-HT、PGE₂和ET-1水平的影响[J]. 针灸临床杂志, 2020, 36(11): 5-9. https://www.cnki.com.cn/Article/CJFDTOTAL-ZJLC202011003.htm WU S, SONG Y Q, ZHANG J J, et al. Effect of Bushen Quyu acupuncture combined with acupoint injection on the levels of 5-HT, PGE2 and ET-1 in the treatment of severe cancer pain in lung cancer with bone metastases[J]Journal of Acupuncture and Moxibustion, 2020, 36(11): 5-9. https://www.cnki.com.cn/Article/CJFDTOTAL-ZJLC202011003.htm
[20]	侯公瑾, 柏正平, 曾普华, 等. 蟾龙镇痛膏对骨转移性癌痛模型大鼠疼痛阈值及血清PGE₂、TNF-α、IL-6、β-EP的影响[J]. 中药新药与临床药理, 2019, 30(10): 1222-1227. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYXY201910012.htm HOU G J, BAI Z P, ZENG P H, et al. Effects of Bufalin analgesic ointment on pain threshold and serum PGE2, TNF-α, IL-6, β-EP in a rat model of bone metastatic cancer pain[J]. Chinese Journal of New Drugs and Clinical Pharmacology, 2019, 30(10): 1222-1227. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYXY201910012.htm
[21]	徐菊娣, 姜峰, 廖志军, 等. 癌痛患者外周血中致痛因子表达与癌痛的关系[J]. 中国优生与遗传杂志, 2020, 28(12): 1432-1437. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYYA202012004.htm XU J D, JIANG F, LIAO Z J, et al. Relationship between the expression of pain-inducing factors in peripheral blood of patients with cancer pain and cancer pain[J]. Chinese Journal of Eugenics and Genetics, 2020, 28(12): 1432-1437. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYYA202012004.htm
[22]	王佛有, 赵岩, 周禹辰, 等. 消癌止痛散对小鼠镇痛作用及对血清β-内啡肽、前列腺素E₂水平的影响[J]. 中国药物经济学, 2021, 16(3): 115-119. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYWA202103030.htm WANG F Y, ZHAO Y, ZHOU Y C, et al. Effects of Xiaoaizhitong Powder on analgesia and serum β-endorphin and prostaglandin E_2 levels in mice[J]. Chinese Journal of Pharmacoeconomics, 2021, 16(3): 115-119. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYWA202103030.htm