加巴喷丁联合阿片类药物应用于癌痛的临床研究
摘要
目的:观察加巴喷丁联合阿片类药物治疗癌痛的临床效果以及对患者免疫功能的影响。方法:采取随机、双盲、对照实验方法, 35例晚期癌症伴疼痛的病人,年龄32-69岁,随机分为3组,即M组:吗啡组,11例;G组:加巴喷丁组,13例;MG组:加巴喷丁+吗啡组,11例;M组给予吗啡,G组给予加巴喷丁,MG组给予加巴喷丁+吗啡药物,达到疼痛缓解时(VAS评分≤3分)维持给药直至观察终点,比较治疗前后的疼痛缓解程度、吗啡日均消耗量、生活质量和副反应,并检测疼痛介质(5-HT、NE)和免疫功能各指标(IgA、IgM、IgG;CD4、CD8、NK细胞)的改变。结果:①疼痛程度的改变:与治疗前相比,3组患者的疼痛程度均有不同程度的缓解, MG组的患者疼痛减轻程度要大于M组(p<0.05)和G组(p<0.05);G组患者疼痛缓解程度最小,绝大多数不能达到3分以下;②吗啡消耗量:MG组的吗啡消耗量比M组少(p<0.05);③3组的疼痛介质在治疗后均低于治疗前(p<0.05);④副反应:MG组的副反应少于M组;⑤生活质量:MG组患者生活质量较M组和G组明显提高;⑥免疫功能指标:3组的各项免疫指标在治疗后高于治疗前(p<0.05)。结论:加巴喷丁联合吗啡有协同镇痛作用,能有效控制癌痛,可以减少吗啡的用量及其副反应,提高患者生活质量,改善患者免疫功能。
Objective: To investigate effective and safety of gabapentin combined morphine for cancer pain
Methods: Thirty-five patiens who suffered pain of cancer disease, VAS scores≥6, aged between 32 and 69yr old, were randomized to three groups:group M, group G and group MG. Group M was treated with morphine tablets ,Group G was treated with gabapentin caps and Group MG was treated with combination of gabapentin caps with morphine tablets, We recorded the pain score by VAS、dose consumption、side effect、quality of life, detected the mediators releated to pain and determine CD4、CD8、NK cell by flow cytometry,determine NE、5-HT、IgG、IgA、IgM by ELISA. Results: Pain relief was better in the group MG compared with the other groups(p<0.05); the morphine consumption of group MG was less more than group M(p<0.05),and gabapentin reduced opioid-related adverse effects; there were no statistical significance in the changes of index of immunity of all patients, and the mediators releated to pain of three groups after treatment were lower than before(p<0.05).
Conclusions: The synergistic effect of gabapentin and morphine can effectively reduce cancer pain, morphine consumption, and morphine-related adverse effects of patiens who suffer from cancer pain;and improved immune function of patients.
Objective: To investigate effective and safety of gabapentin combined morphine for cancer pain
Methods: Thirty-five patiens who suffered pain of cancer disease, VAS scores≥6, aged between 32 and 69yr old, were randomized to three groups:group M, group G and group MG. Group M was treated with morphine tablets ,Group G was treated with gabapentin caps and Group MG was treated with combination of gabapentin caps with morphine tablets, We recorded the pain score by VAS、dose consumption、side effect、quality of life, detected the mediators releated to pain and determine CD4、CD8、NK cell by flow cytometry,determine NE、5-HT、IgG、IgA、IgM by ELISA. Results: Pain relief was better in the group MG compared with the other groups(p<0.05); the morphine consumption of group MG was less more than group M(p<0.05),and gabapentin reduced opioid-related adverse effects; there were no statistical significance in the changes of index of immunity of all patients, and the mediators releated to pain of three groups after treatment were lower than before(p<0.05).
Conclusions: The synergistic effect of gabapentin and morphine can effectively reduce cancer pain, morphine consumption, and morphine-related adverse effects of patiens who suffer from cancer pain;and improved immune function of patients.
引文
[ 1 ] Joranson D,Cleeland C S,Weissman D E,et a1.Opioids for chronic cancer and noncan cer pain : a survey of state medical board members[J].Fed Bull June,1992,79(4):15-49.
[ 2 ] Winston C V . Cancer pain management : principals and practice[M].Parris:Reed educational and pmfessiorud publishing,1996:399-420.
[ 3 ]李仲廉.临床疼痛治疗学[M].天津:天津科学技术出版社,1998:459-460.
[ 4 ]李同度.国内外癌症疼痛控制的过去、现在和未来[J].齐鲁肿瘤杂志,1997,4(3):161-163.
[ 5 ] [5] Li Y,Merrill JD,Mooney K,et a1.Morphine enhances HIV infection of neonatal macrophages.Pediatr Res,2003,54(2):282-288.
[ 6 ]谭冠先主编.疼痛诊疗学[M].第2版.人民卫生出版社.05-07.
[ 7 ]倪家骧.临床疼痛治疗技术[M].北京:科学技术文献出版社, 2003:489-490.
[ 8 ]贺西征,卢乐萍,尹富敏癌痛药物治疗现状的循症医学研Chinese Journal ofClinical Rebabilitation.August 2002.Vo1.6.No.16,2446-47.
[ 9 ] Ian Gilron, Joan M Bailey, Dongsheng Tu et al. Morphine, Gabapentin, orTheir Combination for Neuropathic Pain. The New England Journal of Medicine. Boston: Mar 31, 2005. Vol. 352, Iss. 1324-35.
[10] Twycross R G , Lack S A . Therapeutics in terminal cancer[M].Edinburgh:Churchill Livingstone,1984:11-16.
[11] [ 13 ] Goa KL , Sorkin EM. Gabapentin,A review of its pharmacological properties and clinical potential in epilepsy[J]. Drugs ,1993 ,46 :409-427.
[12] Tuck D,Vollmer KO,Bockbrader H,et al.Dose-linearity of the new anticonvulsant gabapentin after multiple oral doses[J].Eur J Clin Pharmcol,1989,36: 310-314.
[13] Eckhardt K,Amman s,Hofman V,et al. Gabapentio enhances the analgesic effect of morphine in healthy volunteers[J].Anesth Analg,2000,91:185-191.
[14] Jensen TS. Anticonvulsants in neuropathic pain: rationale and clinical evidence[J]. Pain,2003,6(suppl A):61-68.
[15] Rose MA,Kam PCA.Gabapenin:pharmacology and its use in pain management[J].Anaesthesia,2002,57:451-462.
[16]刘国凯,黄宇光,罗爱伦.加巴喷丁用于神经病理性疼痛治疗的研究进展[J].中国临床药理学与治疗学. 2003,Jun , 8(3) :241– 244.
[17] [19]Alparslan Turan, Beyhan Karamanlioglu, Dilek Memis, et al.The Analgesic Effects of Gabapentin After Total Abdominal Hysterectomy[J].Anesth-Analg. 2004,98: 1370-73.
[18] A. Turan, MD, P. F. White , et al.Gabapentin: An Alternative to the Cyclooxygenase-2 Inhibitors for Perioperative Pain Management[J]. Anesth-Analg. 2006 102: 175-181.
[19] A. Fassoulaki, A. Melemeni, A. Paraskeva, et al.Gabapentin attenuates the pressor response to direct laryngoscopy and tracheal intubation[J]. Anaesth., June 1, 2006, 96(6): 769-773.
[20] E. M. Tiippana, K. Hamunen, V. K. Kontinen, et al.Do Surgical Patients Benefit from Perioperative Gabapentin/Pregabalin? A Systematic Review of Efficacy and Safety[J].Anesth-Analg., June 1, 2007,104(6): 1545 - 56.
[21] A. Turan, P. F. White, B. Karamanlioglu, et al.Premedication with Gabapentin: The Effect on Tourniquet Pain and Quality of Intravenous Regional Anesthesia[J].Anesth-Analg, January 1, 2007,104(1): 97 - 101.
[22] A. Turan, G. Kaya, B. Karamanlioglu, et al.Effect of oral gabapentin on postoperative epidural analgesia[J]. Anaesth., February 1, 2006,96(2): 242 - 246.
[23] A. C. Van Elstraete, M. Tirault, T. Lebrun, et al.The Median Effective Dose of Preemptive Gabapentin on Postoperative Morphine Consumption After Posterior Lumbar Spinal Fusion[J].Anesth-Analg., January 1, 2008; 106(1): 305-308.
[24] Rachael K. Seib, MA ,James E. Paul, et al.Preoperative gabapentin for postoperative analgesia: a meta-analysis: [L’administration preoperatoirede gabapentine pour l’analgesie postoperatoire: une meta-analyse] [J]. Can J Anesth, May 1, 2006; 53(5): 461 - 469.
[25] Fassoulak A,Patris K,Sarantopoulos C,et al.The analgesic effect of gabapentin and mexiletine after breast surgery for cancer[J].Anesth-Anale,2002,95:985-991.
[26] Ak?n Takmaz S, Kaymak C, Sare Pehlivan B, et al.Effect of preoperative 900 and 1200 mg single oral dose of gabapentin on postoperative pain relief and tramadol consumption in open cholecystectomy surgery[J] .Agri. 2007 Jul;19(3):32-38.
[27] C. Menigaux, F. Adam, B. Guignard, , et al.Preoperative Gabapentin Decreases Anxiety and Improves Early Functional Recovery from Knee Surgery[J].Anesth-Analg, May 1, 2005,100(5): 1394-99.
[28]瞿慧,王春光,徐建国等.术前服用加巴喷丁对胃癌患者术后曲马多镇痛的影响[J].临床麻醉学杂志.09,2007, 23(9):725-727.
[29] Caraceni A. Gabapentin as an adjuvant to opioid analgesia for neuropathic cancer pain [J ] . J Pain Symptom Manage , 1999 ,17 :441– 445.
[30] Augusto Caraceni, Ernesto Zecca, Cesare Bonezzi,et al Gabapentin for Neuropathic Cancer Pain:A Randomized Controlled Trial From the Gabapentin Cancer Pain Study Group[J] Journal of clinical oncology.2004 JULY ,22(15) 2909-17.
[31] Kader Keskinbora, Pekel AF, Aydinli I.et al.Gabapentin and an opioidcombination versus opioid alone for the management of neuropathic cancer pain: a randomized open trial[J].J Pain Symptom Manage. 2007 Aug;34(2):183-189.
[32] Devulder J . Gabapentin for pain control in cancer patients wound dressing care [J] . J Pain Symptom Manage , 2001 ,22 :622-626.
[33]陈慰峰主编.医学免疫学[M].北京:人民卫生出版社.2001,42-44.
[34]丁桃,胡中,周博凤.慢性疼痛的评估和心理特征[J]. Chinese Medical Research& Clinical,Decembert,2003,Vo1.No.12:50-51.
[35] SpamtSehwable E.Born J.et al.IL-6 Stimulat the HPA axis in man[J].J ChinaEndocrinol matab.1994:19(4)1212-14.
[36] Haubeck HD.Analysis of T suppressor cellmediated tumor escape mechanisms is facilitated by the selective in vitro activation of tumor-specific Ts cells.Hamatol Bluttransfus,1989,32(3):260-264.
[37]孙燕.癌症疼痛的药物治疗[J].齐鲁肿瘤杂志,1997,4(3):164-l65.
[38] Anon.Practice guidelines for cancer pain management.A repo by the American Society of Anesthesiaogists Task Force on Pain Management,Cancer Pain Section[J].Anesthesiology,1996,84(5):l243-57.
[39]刘志民,顾慰萍,周伟华,等.中国癌症疼痛现状调查报告[J].中国肿瘤.1999,8(2):57-60.
[40]郑莹,李德禄,许德风,等.上海市医师对癌症疼痛治疗认识的调查[J].中国肿瘤,2001,l0(7):393-395.
[41] Sinkovics JG.Cytotoxic lymphocytes.Ann Clin Lab Sci,1986,16(6):488-401.
[42]马自力,范士怀,葛来增等.癌症疼痛与机体免疫水平关系的临床研究中国疼痛医学杂志。1999 6(2):133-135.
[43] Kenog A.Supematan t derived from a human hepatocellular Calcinoma cell depresses natural killer cell activity.Can cerImmunol Immunother,1983,15(2):183-186.
1 Goa KL , Sorkin EM. Gabapentin. A review of its pharmacological properties and clinical potential in epilepsy[J]. Drugs ,1993 ,46 :409-427
2 Tuck D,Vollmer KO,Bockbrader H,et al.Dose-linearity of the new anticonvulsant gabapentin after multiple oral doses[J].Eur J Clin Pharmcol,1989,36:A310.
3 Eckhardt K,Amman s,Hofman V,et al. Gabapentio enhances the analgesic effect of morphine in healthy volunteers[J].Anesth Analg,2000,91:185-191.
4 Rose MA,Kam PCA.Gabapenin:pharmacology and its use in pain management[J].Anaesthesia,2002,57:451-462.
5赵欣,于布为.疼痛机制的研究进展[J].上海医学.2007,06:462-465.
6何睿林,蒋宗滨.老年人慢性疼痛的研究进展.中华麻醉在线http://www.csaol.cn 2007,9.
7谭冠先主编.疼痛诊疗学[M].第2版.人民卫生出版社.05-07.
8 Rorarius MGF,Mennander S,Suominen P,et al.Gabapentin for the prevention of postoperative pain after vaginal hysterectomy [J].Pain,2004,111:175-181.
9 Myung Ha Yoon ,Tony L, Yaksh.The Effect of Intrathecal Gabapentin on Pain Behavior and Hemodynamics on the Formalin Test in the Rat[J].Anesth. Analg. 1999,89: 434-437.
10 BennettM I, Simp son KH. Gabapenetin in the treatment of neuropathic pain[J]. PalliatMed,1998, 810 (122) : 93-99.
11 Partridge BJ, Chap lan SR, Sakamoto E, et al. Characterization of the effects of gabapentin and 32isobutyl-gamma-aminobutyric acid on substance P induced thermal hyperalgesia[J]. Anesthesiology 1998, 88 (1) : 196-205.
12 FieldMJ,McCleary S, Hughes J, et al. Gabapentin and p regabalin, but mot morphine and amitrip tyline, block both static and dynamic components of mechanical allodynia induced by strep tozocin in the rat[J]. Pain,1999, 80 (122) : 391-398.
13刘国凯,黄宇光,罗爱伦.加巴喷丁用于神经病理性疼痛治疗的研究进展[J].中国临床药理学与治疗学. 2003,Jun , 8(3) :241– 244
14丁桃,胡中,周博凤.慢性疼痛的评估和心理特征[J]. Chinese Medical Research& Clinical,Decembert,2003,Vo1.No.12:50-551
15 Caraceni A.Gabapentin as an adjuvant to opioid analgesia for neuropathic cancer pain[J].J Pain Symptom Manage,1999,17:441-442
16 Devulder J.Gabapentin for pain control in cancer patients wound dressing care[J]. J Pain Symptom Manage,2001,22:622-626.
17 Wiffen P. Anticonvulsant drugs for acute and chronic pain[DB/CD] . Cochrane Database System Review , 2000 ;3 :001133
18 Dallochio C.Gabapentin vs Amitriptyline in painful diabetic neuropathy.An open-label pilot study [J].J Pain Symptom Manage , 2000 ;20 :280– 285
19 Rowbotham M.Gabapentin for the treatment of postherpetic neuralgia:a randomized controlled trial [J] . J AmMedl Assoc ,1998 ;280 :1837– 1842
20 Solaro C. Low2dose gabapentin combined with either lamotrigine or carbemazepine can be useful therapies for trigeminal neuralgia in multiple sclerosis[J] . Eur J Neurol , 2000 ;44 :45– 48
21 Khan OA. Gabapentin relieves trigeminal neuralgia in multiple sclerosis patients[J] . Neurology , 1998 ;51 :611 - 614
22 Houtchens MK. Open label treatment for pain in multiple scle2rosis[J] . Multi Sclerosis , 1997 ;3 :250– 253、
23 Wheeler DS. Use of gabapentin in the treatment of childhood reflex sympathetic dystrophy[J] . Pediatr Neurol , 2000 ;22 :220- 223
24 Di Trapantin G. Gabapentin in the prophylaxis of migraine : a double2blind randomized placebo2controlled study[J] . La Clin Ther , 2000 ; 145– 149
25 Alparslan Turan, Beyhan Karamanlioglu, Dilek Memis, et al. The Analgesic Effects of Gabapentin After Total Abdominal Hysterectomy Anesth&Analg. 2004 98: 1370-1373.
26 A. Turan, G. Kaya, B. Karamanlioglu, et al. Effect of oral gabapentin on postoperative epidural analgesia.Anaesth., February 1, 2006; 96(2): 242 - 246.
27 Mclean MJ . Safety and tolerability of gabapentin as adjunctive therapy in a large , multicenter study[J ] . Epilepsia , 1999 ;40 :965 - 972
[ 2 ] Winston C V . Cancer pain management : principals and practice[M].Parris:Reed educational and pmfessiorud publishing,1996:399-420.
[ 3 ]李仲廉.临床疼痛治疗学[M].天津:天津科学技术出版社,1998:459-460.
[ 4 ]李同度.国内外癌症疼痛控制的过去、现在和未来[J].齐鲁肿瘤杂志,1997,4(3):161-163.
[ 5 ] [5] Li Y,Merrill JD,Mooney K,et a1.Morphine enhances HIV infection of neonatal macrophages.Pediatr Res,2003,54(2):282-288.
[ 6 ]谭冠先主编.疼痛诊疗学[M].第2版.人民卫生出版社.05-07.
[ 7 ]倪家骧.临床疼痛治疗技术[M].北京:科学技术文献出版社, 2003:489-490.
[ 8 ]贺西征,卢乐萍,尹富敏癌痛药物治疗现状的循症医学研Chinese Journal ofClinical Rebabilitation.August 2002.Vo1.6.No.16,2446-47.
[ 9 ] Ian Gilron, Joan M Bailey, Dongsheng Tu et al. Morphine, Gabapentin, orTheir Combination for Neuropathic Pain. The New England Journal of Medicine. Boston: Mar 31, 2005. Vol. 352, Iss. 1324-35.
[10] Twycross R G , Lack S A . Therapeutics in terminal cancer[M].Edinburgh:Churchill Livingstone,1984:11-16.
[11] [ 13 ] Goa KL , Sorkin EM. Gabapentin,A review of its pharmacological properties and clinical potential in epilepsy[J]. Drugs ,1993 ,46 :409-427.
[12] Tuck D,Vollmer KO,Bockbrader H,et al.Dose-linearity of the new anticonvulsant gabapentin after multiple oral doses[J].Eur J Clin Pharmcol,1989,36: 310-314.
[13] Eckhardt K,Amman s,Hofman V,et al. Gabapentio enhances the analgesic effect of morphine in healthy volunteers[J].Anesth Analg,2000,91:185-191.
[14] Jensen TS. Anticonvulsants in neuropathic pain: rationale and clinical evidence[J]. Pain,2003,6(suppl A):61-68.
[15] Rose MA,Kam PCA.Gabapenin:pharmacology and its use in pain management[J].Anaesthesia,2002,57:451-462.
[16]刘国凯,黄宇光,罗爱伦.加巴喷丁用于神经病理性疼痛治疗的研究进展[J].中国临床药理学与治疗学. 2003,Jun , 8(3) :241– 244.
[17] [19]Alparslan Turan, Beyhan Karamanlioglu, Dilek Memis, et al.The Analgesic Effects of Gabapentin After Total Abdominal Hysterectomy[J].Anesth-Analg. 2004,98: 1370-73.
[18] A. Turan, MD, P. F. White , et al.Gabapentin: An Alternative to the Cyclooxygenase-2 Inhibitors for Perioperative Pain Management[J]. Anesth-Analg. 2006 102: 175-181.
[19] A. Fassoulaki, A. Melemeni, A. Paraskeva, et al.Gabapentin attenuates the pressor response to direct laryngoscopy and tracheal intubation[J]. Anaesth., June 1, 2006, 96(6): 769-773.
[20] E. M. Tiippana, K. Hamunen, V. K. Kontinen, et al.Do Surgical Patients Benefit from Perioperative Gabapentin/Pregabalin? A Systematic Review of Efficacy and Safety[J].Anesth-Analg., June 1, 2007,104(6): 1545 - 56.
[21] A. Turan, P. F. White, B. Karamanlioglu, et al.Premedication with Gabapentin: The Effect on Tourniquet Pain and Quality of Intravenous Regional Anesthesia[J].Anesth-Analg, January 1, 2007,104(1): 97 - 101.
[22] A. Turan, G. Kaya, B. Karamanlioglu, et al.Effect of oral gabapentin on postoperative epidural analgesia[J]. Anaesth., February 1, 2006,96(2): 242 - 246.
[23] A. C. Van Elstraete, M. Tirault, T. Lebrun, et al.The Median Effective Dose of Preemptive Gabapentin on Postoperative Morphine Consumption After Posterior Lumbar Spinal Fusion[J].Anesth-Analg., January 1, 2008; 106(1): 305-308.
[24] Rachael K. Seib, MA ,James E. Paul, et al.Preoperative gabapentin for postoperative analgesia: a meta-analysis: [L’administration preoperatoirede gabapentine pour l’analgesie postoperatoire: une meta-analyse] [J]. Can J Anesth, May 1, 2006; 53(5): 461 - 469.
[25] Fassoulak A,Patris K,Sarantopoulos C,et al.The analgesic effect of gabapentin and mexiletine after breast surgery for cancer[J].Anesth-Anale,2002,95:985-991.
[26] Ak?n Takmaz S, Kaymak C, Sare Pehlivan B, et al.Effect of preoperative 900 and 1200 mg single oral dose of gabapentin on postoperative pain relief and tramadol consumption in open cholecystectomy surgery[J] .Agri. 2007 Jul;19(3):32-38.
[27] C. Menigaux, F. Adam, B. Guignard, , et al.Preoperative Gabapentin Decreases Anxiety and Improves Early Functional Recovery from Knee Surgery[J].Anesth-Analg, May 1, 2005,100(5): 1394-99.
[28]瞿慧,王春光,徐建国等.术前服用加巴喷丁对胃癌患者术后曲马多镇痛的影响[J].临床麻醉学杂志.09,2007, 23(9):725-727.
[29] Caraceni A. Gabapentin as an adjuvant to opioid analgesia for neuropathic cancer pain [J ] . J Pain Symptom Manage , 1999 ,17 :441– 445.
[30] Augusto Caraceni, Ernesto Zecca, Cesare Bonezzi,et al Gabapentin for Neuropathic Cancer Pain:A Randomized Controlled Trial From the Gabapentin Cancer Pain Study Group[J] Journal of clinical oncology.2004 JULY ,22(15) 2909-17.
[31] Kader Keskinbora, Pekel AF, Aydinli I.et al.Gabapentin and an opioidcombination versus opioid alone for the management of neuropathic cancer pain: a randomized open trial[J].J Pain Symptom Manage. 2007 Aug;34(2):183-189.
[32] Devulder J . Gabapentin for pain control in cancer patients wound dressing care [J] . J Pain Symptom Manage , 2001 ,22 :622-626.
[33]陈慰峰主编.医学免疫学[M].北京:人民卫生出版社.2001,42-44.
[34]丁桃,胡中,周博凤.慢性疼痛的评估和心理特征[J]. Chinese Medical Research& Clinical,Decembert,2003,Vo1.No.12:50-51.
[35] SpamtSehwable E.Born J.et al.IL-6 Stimulat the HPA axis in man[J].J ChinaEndocrinol matab.1994:19(4)1212-14.
[36] Haubeck HD.Analysis of T suppressor cellmediated tumor escape mechanisms is facilitated by the selective in vitro activation of tumor-specific Ts cells.Hamatol Bluttransfus,1989,32(3):260-264.
[37]孙燕.癌症疼痛的药物治疗[J].齐鲁肿瘤杂志,1997,4(3):164-l65.
[38] Anon.Practice guidelines for cancer pain management.A repo by the American Society of Anesthesiaogists Task Force on Pain Management,Cancer Pain Section[J].Anesthesiology,1996,84(5):l243-57.
[39]刘志民,顾慰萍,周伟华,等.中国癌症疼痛现状调查报告[J].中国肿瘤.1999,8(2):57-60.
[40]郑莹,李德禄,许德风,等.上海市医师对癌症疼痛治疗认识的调查[J].中国肿瘤,2001,l0(7):393-395.
[41] Sinkovics JG.Cytotoxic lymphocytes.Ann Clin Lab Sci,1986,16(6):488-401.
[42]马自力,范士怀,葛来增等.癌症疼痛与机体免疫水平关系的临床研究中国疼痛医学杂志。1999 6(2):133-135.
[43] Kenog A.Supematan t derived from a human hepatocellular Calcinoma cell depresses natural killer cell activity.Can cerImmunol Immunother,1983,15(2):183-186.
1 Goa KL , Sorkin EM. Gabapentin. A review of its pharmacological properties and clinical potential in epilepsy[J]. Drugs ,1993 ,46 :409-427
2 Tuck D,Vollmer KO,Bockbrader H,et al.Dose-linearity of the new anticonvulsant gabapentin after multiple oral doses[J].Eur J Clin Pharmcol,1989,36:A310.
3 Eckhardt K,Amman s,Hofman V,et al. Gabapentio enhances the analgesic effect of morphine in healthy volunteers[J].Anesth Analg,2000,91:185-191.
4 Rose MA,Kam PCA.Gabapenin:pharmacology and its use in pain management[J].Anaesthesia,2002,57:451-462.
5赵欣,于布为.疼痛机制的研究进展[J].上海医学.2007,06:462-465.
6何睿林,蒋宗滨.老年人慢性疼痛的研究进展.中华麻醉在线http://www.csaol.cn 2007,9.
7谭冠先主编.疼痛诊疗学[M].第2版.人民卫生出版社.05-07.
8 Rorarius MGF,Mennander S,Suominen P,et al.Gabapentin for the prevention of postoperative pain after vaginal hysterectomy [J].Pain,2004,111:175-181.
9 Myung Ha Yoon ,Tony L, Yaksh.The Effect of Intrathecal Gabapentin on Pain Behavior and Hemodynamics on the Formalin Test in the Rat[J].Anesth. Analg. 1999,89: 434-437.
10 BennettM I, Simp son KH. Gabapenetin in the treatment of neuropathic pain[J]. PalliatMed,1998, 810 (122) : 93-99.
11 Partridge BJ, Chap lan SR, Sakamoto E, et al. Characterization of the effects of gabapentin and 32isobutyl-gamma-aminobutyric acid on substance P induced thermal hyperalgesia[J]. Anesthesiology 1998, 88 (1) : 196-205.
12 FieldMJ,McCleary S, Hughes J, et al. Gabapentin and p regabalin, but mot morphine and amitrip tyline, block both static and dynamic components of mechanical allodynia induced by strep tozocin in the rat[J]. Pain,1999, 80 (122) : 391-398.
13刘国凯,黄宇光,罗爱伦.加巴喷丁用于神经病理性疼痛治疗的研究进展[J].中国临床药理学与治疗学. 2003,Jun , 8(3) :241– 244
14丁桃,胡中,周博凤.慢性疼痛的评估和心理特征[J]. Chinese Medical Research& Clinical,Decembert,2003,Vo1.No.12:50-551
15 Caraceni A.Gabapentin as an adjuvant to opioid analgesia for neuropathic cancer pain[J].J Pain Symptom Manage,1999,17:441-442
16 Devulder J.Gabapentin for pain control in cancer patients wound dressing care[J]. J Pain Symptom Manage,2001,22:622-626.
17 Wiffen P. Anticonvulsant drugs for acute and chronic pain[DB/CD] . Cochrane Database System Review , 2000 ;3 :001133
18 Dallochio C.Gabapentin vs Amitriptyline in painful diabetic neuropathy.An open-label pilot study [J].J Pain Symptom Manage , 2000 ;20 :280– 285
19 Rowbotham M.Gabapentin for the treatment of postherpetic neuralgia:a randomized controlled trial [J] . J AmMedl Assoc ,1998 ;280 :1837– 1842
20 Solaro C. Low2dose gabapentin combined with either lamotrigine or carbemazepine can be useful therapies for trigeminal neuralgia in multiple sclerosis[J] . Eur J Neurol , 2000 ;44 :45– 48
21 Khan OA. Gabapentin relieves trigeminal neuralgia in multiple sclerosis patients[J] . Neurology , 1998 ;51 :611 - 614
22 Houtchens MK. Open label treatment for pain in multiple scle2rosis[J] . Multi Sclerosis , 1997 ;3 :250– 253、
23 Wheeler DS. Use of gabapentin in the treatment of childhood reflex sympathetic dystrophy[J] . Pediatr Neurol , 2000 ;22 :220- 223
24 Di Trapantin G. Gabapentin in the prophylaxis of migraine : a double2blind randomized placebo2controlled study[J] . La Clin Ther , 2000 ; 145– 149
25 Alparslan Turan, Beyhan Karamanlioglu, Dilek Memis, et al. The Analgesic Effects of Gabapentin After Total Abdominal Hysterectomy Anesth&Analg. 2004 98: 1370-1373.
26 A. Turan, G. Kaya, B. Karamanlioglu, et al. Effect of oral gabapentin on postoperative epidural analgesia.Anaesth., February 1, 2006; 96(2): 242 - 246.
27 Mclean MJ . Safety and tolerability of gabapentin as adjunctive therapy in a large , multicenter study[J ] . Epilepsia , 1999 ;40 :965 - 972