耳穴穴注缓解癌痛的临床观察及机制研究
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摘要
研究背景:癌症的发病率逐年上升,已成为全球头号杀手,绝大部分癌症病人伴有不同程度的疼痛,癌性疼痛(癌痛)是癌症患者最感痛苦和恐惧的症状之一,严重影响患者的生活质量,虽然WHO(世界卫生组织)推广的三阶梯止痛法能很大程度缓解癌痛,针对顽固性癌痛的侵入性治疗也迅速发展,但由于止痛药物强烈的副作用,病人对药物成瘾性、耐药性、个体差异及有创治疗的恐惧,“让癌症病人不痛”这一目标一直未能实现,寻找一种安全有效、副作用小、经济方便的止痛方法成为临床研究的重要内容。针灸具有较好的止痛作用,近年来用于癌痛治疗取得较好疗效,对针灸治疗癌痛的机制也有初步的探索,耳针及穴位注射是临床常用的针灸止痛方法,有较好的疗效,各地学者对耳针和穴位注射的研究较多,但高质量的、样本含量大的、随机对照的临床研究寥寥可数。
目的:本研究采用耳穴穴注野木瓜注射液(IS)治疗中重度癌痛患者,观察其临床疗效,通过记录治疗前后生活质量(QOL)的变化情况,突出其与西药相比镇痛的优势所在,通过检测治疗前及治疗结束后β-EP(β-内啡肽)、ET-1(内皮素-1)、PGE2(前列腺素E2)水平,初步探索耳穴穴注野木瓜注射液的作用机制。
方法:临床选取48例中重度癌痛患者,以疼痛程度分层并于层内随机分为耳穴穴注IS的治疗组23例,口服奥施康定对照组25例,7天为一个疗程。分别观察其镇痛起效时间、镇痛维持时间、总体有效率,进行组间比较,对两组患者治疗前及治疗结束后进行KPS评分(卡氏行为状态评分,附表2)、BPQ(简明疼痛调查表,附表4)调查、抽取静脉血检测β—EP、ET—1、PGE2含量,进行组内、组间比较。
结果:
1、耳穴穴注IS对癌痛有较好疗效:
①治疗组总缓解率为91.3%,中度以上缓解率为78.3%,与对照组相比总体缓解率和中度以上缓解率差异无统计学意义(P＞0.05);
②治疗组使用奥施康定总量为4620mg,中度疼痛为280mg,重度疼痛为4340mg;对照组为用药总量为11340mg,中度疼痛为1120mg,重度疼痛为10220mg;两者有明显差异,说明耳穴穴注IS有切实的镇痛作用;
③镇痛起效时间治疗组平均为17.65±6.91min,对照组平均为31.36±6.60min,两组比较差异有统计学意义(P＜0.01),耳穴穴注IS较对照组镇痛起效更快;
④镇痛维持时间治疗组平均为18.21±1.33h,对照组为11.76±0.99h,两组比较差异有统计学意义(P＜0.01),耳穴穴注IS较口服奥施康定镇痛维持时间更久;
2、耳穴穴注IS对癌痛患者的生活质量有较好的改善作用:
①KPS评分治疗组治疗前为63.04±7.029分,治疗后为70.87±7.332分,对照组治疗前KPS评分为64.00±9.129分,治疗后为70.80±7.594分,两组前后比较差异均有统计学意义(P＜0.01),说明两种镇痛方法均能改善患者的KPS评分;同时对治疗后两组间KPS评分进行比较,差异无统计学意义(P＞0.05),说明两种镇痛方法对改善患者行为状态作用相似。
②BPQ调查显示两组治疗后在日常生活、情绪、行走能力、睡眠、生活乐趣和QOL的总积分上均较治疗前明显改善,前后比较差异有统计学意义(P＜0.05);同时治疗后两组间比较治疗组在日常生活、情绪、睡眠、生活乐趣和QOL的总积分上较对照组改善更加明显,两组比较差异有统计学意义(P＜0.05),说明耳穴穴注IS在改善患者生活质量上与口服奥施康定相比有一定优势。
③治疗组23例患者中,研究中暂未发现耳穴穴注的不良反应;对照组便秘9例(36%),恶心、呕吐6例(24%),头晕3例(12%),其中有1例出现神志不清的吗啡中毒现象。
3、耳穴穴注IS缓解癌痛可能与提高体内β—EP含量和降低ET-1水平有关。
①两组治疗前β—EP含量较正常值偏高,治疗组治疗后β—EP明显升高达433.415±209.337pg/ml,前后比较差异有统计学意义(P＜0.01);而对照组治疗后β—EP含量有所降低,为227.626±170.651pg/ml,差异有统计学意义(P＜0.05);治疗后两组间比较显示治疗组β—EP含量明显较高,差异有统计学意义(P＜0.01)。
②两组治疗前ET-1水平较正常值偏高,治疗组治疗后ET-1含量下降达124.477±41.693pg/ml,前后比较差异有统计学意义(P＜0.01);对照组ET-1含量无明显变化(P＞0.05);两组间比较治疗后ET-1水平差异有统计学意义(P＜0.01)。
结论:耳穴穴注IS治疗癌痛有较好的临床疗效,治疗组与对照组临床疗效相当,而耳穴穴注IS镇痛起效时间更快、镇痛维持时间更长;耳穴穴注IS能更较好地改善患者的生活质量且基本无副作用;耳穴穴注IS缓解癌痛的机制可能与提高体内β—EP水平和降低ET-1水平有关。
Study Background:The frequency of cancer is rising year after year.Being the first reason of death of mankind in the world,most of patients with cancer suffer from different grades of cancer pain,it is one of the most distressed and most worried symptom for a cancer patient,and it seriously influences the patients' quality of life.Although The WHO Cancer Pain Relief Program such as three step analgesic ladder can relieve some pain of the patient,and the inserted remedy that can relieve intractable pain is developing rapidly,but because of the strong side-effect of the anodyne or afraid of drug addiction and drug-fast and so on,the target that "no pain of the cancer patient" can not be completed until now。Therefore,the focus of current research is to find an analgesia,which is safe,active,minimal side-effects,economic and convenience.Acupuncture is a good way to relieve pain,evenmore,previous reports showed that acupuncture was a very effctive treatment used in cancer patients for relieving pain,some researches were refered to the mechanisms of the acupuncture used in cancer pain reliveing。Ear acupuncture and injection ad acumen are the frequent used and effective treatments to relieve cancer pain in clinic,there were more studies about ear acupuncture and injection ad acumen than other acupuncture means,but little of those researches were high-quailty,randomly compared or with large samples.
Objective:First to observe the analgesic effect of the treatment--the ear acupoints injection with stauntoniae in management of the moderate and severe cancer pain.Second through investing the QOL of the patients to explain the ear acupoints injection is better than western medicine in some way.Moreover to study the mechanism of the ear acupoints injection with stauntoniae to relieve cancer pain.
Methods:In the clinical study,48 patients with moderate or severe cancer pain were observed,stratified the patients by different pain degrees,and then randomly divided into two groups,23 in the treating group were treated by ear acupoints injection with stauntoniae and 25 in the control group took Oxycodon tablets orally to relieve cancer pain,time of the therapy was 7 days.Evaluated outcomes included analgesic effective rate,time for onset of analgesic effect,duration of analgesic effect,KPS,BPQ andβ-EP、ET-1、PGE2 contents in peripheral blood were determined.
Results:
1、Ear acupoints injection with stauntoniae was effective to relieve cancer pain.
①In the treating group the total effective rate was 91.3%,the obvious remission rate was 78.3%,compared with the control group,the result showed there wasn't statistical significant difference in total effective rate and obvious remission rate(P＞0.05).
②The total dosage of oxycontin in the treating group was 4620mg,moderate pain 280mg and severe cancer pain 4340mg;while in the control group total dosage was 11340mg,moderate pain 1120mg and severe pain 10220mg.The result showed significant difference between them,therefore Ear acupoints injection with stauntoniae was surely effective in relieving cancer pain.
③Mean time for onset of analgesic was 17.65±6.91min in the treating group,but 31.36±6.60min in the control group,there was statistical difference in mean time for onset of analgesic(P＜0.01).Ear acupoints injection with stauntoniae worked more quickly.
④The mean duration of analgesic effect was 18.21±1.33h in the treating group,11.76±0.99h in the control group,compared the tow groups,there was statistical significant difference(p＜0.01),the analgesic effect of ear acupoints injection with stauntoniae could maintain longer time.
2、Ear acupoints injection with stauntoniae showed better effect on the improvement of QOL for cancer pain patients.
①Mean KPS of the treating group was 63.04±7.029 before the treatment,70.87±7.332 after the treatment,and in the control group it was 64.00±9.129 before the treatment,70.80±7.594 after the treatment,both of the two groups there were statistical significant differences fore-and-aft(P＜0.01),both of the treatments could improve the patients' KPS.But compared the two groups after treatment,there wasn't statistical difference(P＞0.05);
②Both of the two treatments promoted the daily life,emotion,walking ability,sleeping,life joy and total integral through investigating the BPQ, compared with those after treatment,there were statistical differences pro-and-aft(P＜0.05);While daily life,emotion,sleeping,life joy and total integral of the treating group were better than the control group after treatment,there were statistical significant differences(P＜0.05);Ear acupoints injection with stauntoniae was better to improve patients' QOL.
③There were 23 cancer pain patients in the treating group,none of the side effect was observed in the research;while in the control group 9 patients had the symptom of constipation,6 patients with nausea and vomiting,3 patients with dizziness,even 1 patient had the symptom of morphine poisoning. 3、One of the mechanisms of ear acupoints injection with stauntoniae maybe relate to rise the level ofβ-EP and decrease the level of ET-1.
①The levels ofβ-EP was higher than normal value in both of the two groups before treatment,then in the treating group the level ofβ-EP rised to 433.415±209.337pg/ml after treatment,there was statistical significant difference in pre and post treatment(P＜0.01).While in the control group the level ofβ-EP decreased,showed statistical difference(P＜0.05);compared with the levels ofβ-EP post treatment between the two groups,it showed statistical difference(P＜0.01) too.
②The levels of ET-1 were higher than normal value also in both of the groups pre-treatment,post treatment the level of ET-1 dropped to 124.477±41.693pg/ml,there was statistical significant difference in pre and post treatment(P＜0.01);However in the control group the level showed no change(P＞0.05);The levels of the two groups were statistical difference after treatment(P＜0.01).
Conclusion:Ear acupoints injection with stauntoniae was effective to relieve cancer pain,the treating group had similar effect with the control group,but ear acupoints injection worked more quickly and longly;ear acupoints injection with stauntoniae improved the QOL better than the Oxycontin,and had slight side effect;the mechanism of ear acupoints injection with stauntoniae maybe relate to rise the level ofβ-EP and decrease the level of ET-1 in the body of the patients.
目的:本研究采用耳穴穴注野木瓜注射液(IS)治疗中重度癌痛患者,观察其临床疗效,通过记录治疗前后生活质量(QOL)的变化情况,突出其与西药相比镇痛的优势所在,通过检测治疗前及治疗结束后β-EP(β-内啡肽)、ET-1(内皮素-1)、PGE2(前列腺素E2)水平,初步探索耳穴穴注野木瓜注射液的作用机制。
方法:临床选取48例中重度癌痛患者,以疼痛程度分层并于层内随机分为耳穴穴注IS的治疗组23例,口服奥施康定对照组25例,7天为一个疗程。分别观察其镇痛起效时间、镇痛维持时间、总体有效率,进行组间比较,对两组患者治疗前及治疗结束后进行KPS评分(卡氏行为状态评分,附表2)、BPQ(简明疼痛调查表,附表4)调查、抽取静脉血检测β—EP、ET—1、PGE2含量,进行组内、组间比较。
结果:
1、耳穴穴注IS对癌痛有较好疗效:
①治疗组总缓解率为91.3%,中度以上缓解率为78.3%,与对照组相比总体缓解率和中度以上缓解率差异无统计学意义(P＞0.05);
②治疗组使用奥施康定总量为4620mg,中度疼痛为280mg,重度疼痛为4340mg;对照组为用药总量为11340mg,中度疼痛为1120mg,重度疼痛为10220mg;两者有明显差异,说明耳穴穴注IS有切实的镇痛作用;
③镇痛起效时间治疗组平均为17.65±6.91min,对照组平均为31.36±6.60min,两组比较差异有统计学意义(P＜0.01),耳穴穴注IS较对照组镇痛起效更快;
④镇痛维持时间治疗组平均为18.21±1.33h,对照组为11.76±0.99h,两组比较差异有统计学意义(P＜0.01),耳穴穴注IS较口服奥施康定镇痛维持时间更久;
2、耳穴穴注IS对癌痛患者的生活质量有较好的改善作用:
①KPS评分治疗组治疗前为63.04±7.029分,治疗后为70.87±7.332分,对照组治疗前KPS评分为64.00±9.129分,治疗后为70.80±7.594分,两组前后比较差异均有统计学意义(P＜0.01),说明两种镇痛方法均能改善患者的KPS评分;同时对治疗后两组间KPS评分进行比较,差异无统计学意义(P＞0.05),说明两种镇痛方法对改善患者行为状态作用相似。
②BPQ调查显示两组治疗后在日常生活、情绪、行走能力、睡眠、生活乐趣和QOL的总积分上均较治疗前明显改善,前后比较差异有统计学意义(P＜0.05);同时治疗后两组间比较治疗组在日常生活、情绪、睡眠、生活乐趣和QOL的总积分上较对照组改善更加明显,两组比较差异有统计学意义(P＜0.05),说明耳穴穴注IS在改善患者生活质量上与口服奥施康定相比有一定优势。
③治疗组23例患者中,研究中暂未发现耳穴穴注的不良反应;对照组便秘9例(36%),恶心、呕吐6例(24%),头晕3例(12%),其中有1例出现神志不清的吗啡中毒现象。
3、耳穴穴注IS缓解癌痛可能与提高体内β—EP含量和降低ET-1水平有关。
①两组治疗前β—EP含量较正常值偏高,治疗组治疗后β—EP明显升高达433.415±209.337pg/ml,前后比较差异有统计学意义(P＜0.01);而对照组治疗后β—EP含量有所降低,为227.626±170.651pg/ml,差异有统计学意义(P＜0.05);治疗后两组间比较显示治疗组β—EP含量明显较高,差异有统计学意义(P＜0.01)。
②两组治疗前ET-1水平较正常值偏高,治疗组治疗后ET-1含量下降达124.477±41.693pg/ml,前后比较差异有统计学意义(P＜0.01);对照组ET-1含量无明显变化(P＞0.05);两组间比较治疗后ET-1水平差异有统计学意义(P＜0.01)。
结论:耳穴穴注IS治疗癌痛有较好的临床疗效,治疗组与对照组临床疗效相当,而耳穴穴注IS镇痛起效时间更快、镇痛维持时间更长;耳穴穴注IS能更较好地改善患者的生活质量且基本无副作用;耳穴穴注IS缓解癌痛的机制可能与提高体内β—EP水平和降低ET-1水平有关。
Study Background:The frequency of cancer is rising year after year.Being the first reason of death of mankind in the world,most of patients with cancer suffer from different grades of cancer pain,it is one of the most distressed and most worried symptom for a cancer patient,and it seriously influences the patients' quality of life.Although The WHO Cancer Pain Relief Program such as three step analgesic ladder can relieve some pain of the patient,and the inserted remedy that can relieve intractable pain is developing rapidly,but because of the strong side-effect of the anodyne or afraid of drug addiction and drug-fast and so on,the target that "no pain of the cancer patient" can not be completed until now。Therefore,the focus of current research is to find an analgesia,which is safe,active,minimal side-effects,economic and convenience.Acupuncture is a good way to relieve pain,evenmore,previous reports showed that acupuncture was a very effctive treatment used in cancer patients for relieving pain,some researches were refered to the mechanisms of the acupuncture used in cancer pain reliveing。Ear acupuncture and injection ad acumen are the frequent used and effective treatments to relieve cancer pain in clinic,there were more studies about ear acupuncture and injection ad acumen than other acupuncture means,but little of those researches were high-quailty,randomly compared or with large samples.
Objective:First to observe the analgesic effect of the treatment--the ear acupoints injection with stauntoniae in management of the moderate and severe cancer pain.Second through investing the QOL of the patients to explain the ear acupoints injection is better than western medicine in some way.Moreover to study the mechanism of the ear acupoints injection with stauntoniae to relieve cancer pain.
Methods:In the clinical study,48 patients with moderate or severe cancer pain were observed,stratified the patients by different pain degrees,and then randomly divided into two groups,23 in the treating group were treated by ear acupoints injection with stauntoniae and 25 in the control group took Oxycodon tablets orally to relieve cancer pain,time of the therapy was 7 days.Evaluated outcomes included analgesic effective rate,time for onset of analgesic effect,duration of analgesic effect,KPS,BPQ andβ-EP、ET-1、PGE2 contents in peripheral blood were determined.
Results:
1、Ear acupoints injection with stauntoniae was effective to relieve cancer pain.
①In the treating group the total effective rate was 91.3%,the obvious remission rate was 78.3%,compared with the control group,the result showed there wasn't statistical significant difference in total effective rate and obvious remission rate(P＞0.05).
②The total dosage of oxycontin in the treating group was 4620mg,moderate pain 280mg and severe cancer pain 4340mg;while in the control group total dosage was 11340mg,moderate pain 1120mg and severe pain 10220mg.The result showed significant difference between them,therefore Ear acupoints injection with stauntoniae was surely effective in relieving cancer pain.
③Mean time for onset of analgesic was 17.65±6.91min in the treating group,but 31.36±6.60min in the control group,there was statistical difference in mean time for onset of analgesic(P＜0.01).Ear acupoints injection with stauntoniae worked more quickly.
④The mean duration of analgesic effect was 18.21±1.33h in the treating group,11.76±0.99h in the control group,compared the tow groups,there was statistical significant difference(p＜0.01),the analgesic effect of ear acupoints injection with stauntoniae could maintain longer time.
2、Ear acupoints injection with stauntoniae showed better effect on the improvement of QOL for cancer pain patients.
①Mean KPS of the treating group was 63.04±7.029 before the treatment,70.87±7.332 after the treatment,and in the control group it was 64.00±9.129 before the treatment,70.80±7.594 after the treatment,both of the two groups there were statistical significant differences fore-and-aft(P＜0.01),both of the treatments could improve the patients' KPS.But compared the two groups after treatment,there wasn't statistical difference(P＞0.05);
②Both of the two treatments promoted the daily life,emotion,walking ability,sleeping,life joy and total integral through investigating the BPQ, compared with those after treatment,there were statistical differences pro-and-aft(P＜0.05);While daily life,emotion,sleeping,life joy and total integral of the treating group were better than the control group after treatment,there were statistical significant differences(P＜0.05);Ear acupoints injection with stauntoniae was better to improve patients' QOL.
③There were 23 cancer pain patients in the treating group,none of the side effect was observed in the research;while in the control group 9 patients had the symptom of constipation,6 patients with nausea and vomiting,3 patients with dizziness,even 1 patient had the symptom of morphine poisoning. 3、One of the mechanisms of ear acupoints injection with stauntoniae maybe relate to rise the level ofβ-EP and decrease the level of ET-1.
①The levels ofβ-EP was higher than normal value in both of the two groups before treatment,then in the treating group the level ofβ-EP rised to 433.415±209.337pg/ml after treatment,there was statistical significant difference in pre and post treatment(P＜0.01).While in the control group the level ofβ-EP decreased,showed statistical difference(P＜0.05);compared with the levels ofβ-EP post treatment between the two groups,it showed statistical difference(P＜0.01) too.
②The levels of ET-1 were higher than normal value also in both of the groups pre-treatment,post treatment the level of ET-1 dropped to 124.477±41.693pg/ml,there was statistical significant difference in pre and post treatment(P＜0.01);However in the control group the level showed no change(P＞0.05);The levels of the two groups were statistical difference after treatment(P＜0.01).
Conclusion:Ear acupoints injection with stauntoniae was effective to relieve cancer pain,the treating group had similar effect with the control group,but ear acupoints injection worked more quickly and longly;ear acupoints injection with stauntoniae improved the QOL better than the Oxycontin,and had slight side effect;the mechanism of ear acupoints injection with stauntoniae maybe relate to rise the level ofβ-EP and decrease the level of ET-1 in the body of the patients.
引文
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