阿片药物耐受病人疼痛阈值变化的临床研究
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摘要
目的:通过观察阿片药物耐受的癌痛病人疼痛程度、疼痛阈值的变化以及其神经病理性疼痛的发生情况,揭示阿片药物导致癌痛病人痛觉敏化的临床现象。方法:采用前瞻性队列研究,将2016年9月至2017年9月疼痛科就诊的41例中、重度癌痛病人按照每日阿片药物摄入剂量进行分组(不同阿片药物按照镇痛作用等效剂量进行换算),每日阿片药物摄入剂量相当于口服吗啡剂量<60 mg者为阿片未耐受组,每日阿片类药物摄入剂量相当于口服吗啡量≥60 mg且维持该剂量超过1周者为阿片耐受组。比较两组癌痛病人的疼痛程度、疼痛阈值以及神经病理性疼痛的发生率。结果:阿片耐受组纳入病人19例,阿片未耐受组纳入病人22例。两组癌痛病人的视觉模拟评分(visual analogue scale, VAS)分别为8.2±1.3(阿片耐受组)和7.6±2.2(阿片未耐受组),两组无显著差异(P> 0.05);阿片耐受组病人的疼痛阈值为97.7±25.6 g,与阿片未耐受组158.7±57.4 g相比,明显降低(P <0.05);且阿片耐受组癌痛病人的神经病理性疼痛发生率高于阿片未耐受组(27.2%vs. 19.2%)。结论:虽然阿片药物耐受的癌痛病人与阿片药物未耐受的癌痛病人疼痛程度相同,但是阿片药物耐受的癌痛病人疼痛阈值明显降低,更易发生痛觉敏化。
Objective:To study opioid-induced hyperalgesia in cancer pain patients with opioid tolerance by investigating the pain intensity, the change of pain thresholds and the incidence of neuropathic pain. Methods: A prospective cohort study was performed. Patients diagnosed with moderate to severe cancer pain in pain department from September 2016 to September 2017 were divided into two groups based on the dosage use of oral morphine group one was with less than 60 mg of morphine daily and group two with 60 mg or more daily for a week or longer. VAS was used to examine pain intensity, pain thresholds were measured by von Frey and the incidence of neuropathic pain was evaluated by DN4. Results: A total of 41 patients were included, 19 in group one and 22 in group two. VAS was 8.2±1.3 in group one and 7.6±2.2 in group two, and there was no significant difference in pain intensity between the two groups(P > 0.05). Compared with group one, pain thresholds was significantly decreased in group two(97.7±25.6g vs. 158.7±57.4 g, P < 0.05). Incidence of neuropathic pain in group two was higher than that in Group one(27.2% vs. 19.2%). Conclusion: Although there was no difference in pain intensity between opioid tolerance patients and opioid na?ve patients, the pain threshold of opioid tolerance patients was lower than opioid na?ve patients and opioid tolerance patients are more likely to experience hyperalgesia.
Objective:To study opioid-induced hyperalgesia in cancer pain patients with opioid tolerance by investigating the pain intensity, the change of pain thresholds and the incidence of neuropathic pain. Methods: A prospective cohort study was performed. Patients diagnosed with moderate to severe cancer pain in pain department from September 2016 to September 2017 were divided into two groups based on the dosage use of oral morphine group one was with less than 60 mg of morphine daily and group two with 60 mg or more daily for a week or longer. VAS was used to examine pain intensity, pain thresholds were measured by von Frey and the incidence of neuropathic pain was evaluated by DN4. Results: A total of 41 patients were included, 19 in group one and 22 in group two. VAS was 8.2±1.3 in group one and 7.6±2.2 in group two, and there was no significant difference in pain intensity between the two groups(P > 0.05). Compared with group one, pain thresholds was significantly decreased in group two(97.7±25.6g vs. 158.7±57.4 g, P < 0.05). Incidence of neuropathic pain in group two was higher than that in Group one(27.2% vs. 19.2%). Conclusion: Although there was no difference in pain intensity between opioid tolerance patients and opioid na?ve patients, the pain threshold of opioid tolerance patients was lower than opioid na?ve patients and opioid tolerance patients are more likely to experience hyperalgesia.
引文
[1]Coleman MP.Cancer survival:global surveillance will stimulate health policy and improve equity[J].Lancet,2014,383:568-573.
[2]宋莉,吴超然,刘慧,等.关于华西医院肿瘤中心住院患者癌痛情况的调查分析[J].中国疼痛医学杂志,2014,20(8):630-634.
[3]Roeckel LA,Le CG,Gavériaux-Ruff C,et al.Opioid-induced hyperalgesia.Cellular and molecular mechanisms[J].Neuroscience,2016,338:160-182.
[4]Swarm RA,Abernethy AP,Anghelescu DL,et al.Adult cancer pain[J].J Natl Compr Canc Netw,2013,11:992.
[5]谭冠先,疼痛诊疗学[M].第二版.北京:人民卫生出版社,2005,10-11.
[6]Dougherty PM,Cata JP,Cordella JV,et al.Taxolinduced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients[J].Pain,2004,109:132-142.
[7]Bouhassira D,Attal N,Alchaar H,et al.Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire(DN4)[J].Pain,2005,114:29-36.
[8]张金,李润芝,牛小媛.中文版DN4神经病理性疼痛量表的制定与评估[J].中国疼痛医学杂志,2016,22(8):628-631.
[9]Rossbach MJ.Ueber die Gew?hnung an Gifte[J].Archiv Für Die Gesamte Physiologie Des Menschen Und Der Tiere,1970,21:213-225.
[10]李小梅,董艳娟,李慧莉,等.阿片耐受与慢性癌痛的阿片类药物治疗[J].中国疼痛医学杂志,2012,18(8):561-565.
[11]Silverman SM.Opioid induced hyperalgesia:clinical implications for the pain practitioner[J].Pain Physician,2009,12:679.
[12]宋莉,杨邦祥,银燕,等.慢性吗啡注射对幼年大鼠痛行为学的影响[J].四川大学学报(医学版),2013,44:209-212.
[13]Campillo A,Gonzálezcuello A,Caba?ero D,et al.Increased spinal dynorphin levels and phosphoextracellular signal-regulated kinases 1 and 2 and cFos immunoreactivity after surgery under remifentanil anesthesia in mice[J].Mol Pharmacol,2010,77:185-194.
[14]Virk MS,Williams JT.Agonist-specific regulation of mu-opioid receptor desensitization and recovery from desensitization[J].Mol Pharmacol,2008,73:1301-1308.
[15]Wang S,Tian Y,Song L,et al.Exacerbated Mechanical Hyperalgesia in Rats with Genetically Predisposed Depressive Behavior:Role of Melatonin and NMDAReceptors[J].Pain?,2012,153:2448-2457.
[16]Ramasubbu C,Gupta A.Pharmacological treatment of opioid-induced hyperalgesia:a review of the evidence[J].J Pain Palliat Care Pharmacother,2011,25:219.
[17]Song L,Wu C,Zuo Y.Melatonin prevents morphineinduced hyperalgesia and tolerance in rats:role of protein kinase C and N-methyl-D-aspartate receptors[J].BMC Anesthesiol,2015,15:12.
[18]Fan L,Li S,Tian XM,et al.Current Status of Malignant Neuropathic Pain in Chinese Patients with Cancer:Report of a Hospital-based Investigation of Prevalence,Etiology,Assessment,and Treatment[J].Pain Pract,2017,17:88.
[19]郑碧鑫,宋莉,刘慧.阿片类药物诱导痛觉过敏的诊断及防治研究进展[J].中国疼痛医学杂志,2016,22(10):777-780.
[20]Mao J.Clinical Diagnosis of Opioid-Induced Hyperalgesia[J].Region Anesth Pain Med,2015,40:663.
[2]宋莉,吴超然,刘慧,等.关于华西医院肿瘤中心住院患者癌痛情况的调查分析[J].中国疼痛医学杂志,2014,20(8):630-634.
[3]Roeckel LA,Le CG,Gavériaux-Ruff C,et al.Opioid-induced hyperalgesia.Cellular and molecular mechanisms[J].Neuroscience,2016,338:160-182.
[4]Swarm RA,Abernethy AP,Anghelescu DL,et al.Adult cancer pain[J].J Natl Compr Canc Netw,2013,11:992.
[5]谭冠先,疼痛诊疗学[M].第二版.北京:人民卫生出版社,2005,10-11.
[6]Dougherty PM,Cata JP,Cordella JV,et al.Taxolinduced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients[J].Pain,2004,109:132-142.
[7]Bouhassira D,Attal N,Alchaar H,et al.Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire(DN4)[J].Pain,2005,114:29-36.
[8]张金,李润芝,牛小媛.中文版DN4神经病理性疼痛量表的制定与评估[J].中国疼痛医学杂志,2016,22(8):628-631.
[9]Rossbach MJ.Ueber die Gew?hnung an Gifte[J].Archiv Für Die Gesamte Physiologie Des Menschen Und Der Tiere,1970,21:213-225.
[10]李小梅,董艳娟,李慧莉,等.阿片耐受与慢性癌痛的阿片类药物治疗[J].中国疼痛医学杂志,2012,18(8):561-565.
[11]Silverman SM.Opioid induced hyperalgesia:clinical implications for the pain practitioner[J].Pain Physician,2009,12:679.
[12]宋莉,杨邦祥,银燕,等.慢性吗啡注射对幼年大鼠痛行为学的影响[J].四川大学学报(医学版),2013,44:209-212.
[13]Campillo A,Gonzálezcuello A,Caba?ero D,et al.Increased spinal dynorphin levels and phosphoextracellular signal-regulated kinases 1 and 2 and cFos immunoreactivity after surgery under remifentanil anesthesia in mice[J].Mol Pharmacol,2010,77:185-194.
[14]Virk MS,Williams JT.Agonist-specific regulation of mu-opioid receptor desensitization and recovery from desensitization[J].Mol Pharmacol,2008,73:1301-1308.
[15]Wang S,Tian Y,Song L,et al.Exacerbated Mechanical Hyperalgesia in Rats with Genetically Predisposed Depressive Behavior:Role of Melatonin and NMDAReceptors[J].Pain?,2012,153:2448-2457.
[16]Ramasubbu C,Gupta A.Pharmacological treatment of opioid-induced hyperalgesia:a review of the evidence[J].J Pain Palliat Care Pharmacother,2011,25:219.
[17]Song L,Wu C,Zuo Y.Melatonin prevents morphineinduced hyperalgesia and tolerance in rats:role of protein kinase C and N-methyl-D-aspartate receptors[J].BMC Anesthesiol,2015,15:12.
[18]Fan L,Li S,Tian XM,et al.Current Status of Malignant Neuropathic Pain in Chinese Patients with Cancer:Report of a Hospital-based Investigation of Prevalence,Etiology,Assessment,and Treatment[J].Pain Pract,2017,17:88.
[19]郑碧鑫,宋莉,刘慧.阿片类药物诱导痛觉过敏的诊断及防治研究进展[J].中国疼痛医学杂志,2016,22(10):777-780.
[20]Mao J.Clinical Diagnosis of Opioid-Induced Hyperalgesia[J].Region Anesth Pain Med,2015,40:663.