Intervention Review

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Pharmacotherapy for the prevention of chronic pain after surgery in adults

  1. Luis Enrique Chaparro1,
  2. Shane A Smith2,
  3. R Andrew Moore3,
  4. Philip J Wiffen3,
  5. Ian Gilron4,*

Editorial Group: Cochrane Pain, Palliative and Supportive Care Group

Published Online: 24 JUL 2013

Assessed as up-to-date: 17 JUL 2013

DOI: 10.1002/14651858.CD008307.pub2

How to Cite

Chaparro LE, Smith SA, Moore RA, Wiffen PJ, Gilron I. Pharmacotherapy for the prevention of chronic pain after surgery in adults. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD008307. DOI: 10.1002/14651858.CD008307.pub2.

Author Information

  1. 1

    Hospital Pablo Tobon Uribe, Anesthesiology Department, Medellin, Colombia

  2. 2

    Queen's University, Department of Anesthesiology & Perioperative Medicine, Kingston, Canada

  3. 3

    University of Oxford, Pain Research and Nuffield Department of Clinical Neurosciences, Oxford, Oxfordshire, UK

  4. 4

    Queen's University, Departments of Anesthesiology & Perioperative Medicine & Biomedical & Molecular Sciences, Kingston, Ontario, Canada

*Ian Gilron, Departments of Anesthesiology & Perioperative Medicine & Biomedical & Molecular Sciences, Queen's University, 76 Stuart Street, Victory 2 Pavillion, Kingston, Ontario, K7L 2V7, Canada.

Publication History

  1. Publication Status: New
  2. Published Online: 24 JUL 2013



References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
Amr 2010 {published data only}
  • Amr YM, Yousef AA. Evaluation of efficacy of the perioperative administration of Venlafaxine or gabapentin on acute and chronic postmastectomy pain. The Clinical Journal of Pain 2010;26(5):381-5. [PUBMED: 20473044]
Bergeron 2009 {published data only}
  • Bergeron SG, Kardash KJ, Huk OL, Zukor DJ, Antoniou J. Perioperative dexamethasone does not affect functional outcome in total hip arthroplasty. Clinical Orthopaedics and Related Research 2009;467(6):1463-7. [PUBMED: 19224304]
Brogly 2008 {published data only}
  • Brogly N, Wattier JM, Andrieu G, Peres D, Robin E, Kipnis E, et al. Gabapentin attenuates late but not early postoperative pain after thyroidectomy with superficial cervical plexus block. Anesthesia and Analgesia 2008;107(5):1720-5. [PUBMED: 18931238]
Burke 2010 {published data only}
  • Burke SM, Shorten GD. Perioperative pregabalin improves pain and functional outcomes 3 months after lumbar discectomy. Anesthesia and Analgesia 2010;110(4):1180-5. [PUBMED: 20103545]
Buvanendran 2010 {published data only}
  • Buvanendran A, Kroin JS, Della Valle CJ, Kari M, Moric M, Tuman KJ. Perioperative oral pregabalin reduces chronic pain after total knee arthroplasty: a prospective, randomized, controlled trial. Anesthesia and Analgesia 2010;110(1):199-207. [PUBMED: 19910619]
Chan 2011 {published data only}
Chaparro 2010 {published data only}
  • Chaparro LE, Munoz Y, Gallo CA, Alvarez HA, Restrepo SM, Perez N, Restrepo L. Pain and Sensory Symptoms Following Augmentation Mammoplasty: A Long Term Follow-Up Study with Intraoperative Ketamine Use [Dolor y síntomas sensoriales después de mamoplastia estética de aumento: un estudio de seguimiento a largo plazo posterior al uso intraoperatorio de ketamina]. Revista Colombiana Anestesiologia 2010;38(2):204-12.
Clarke 2009 {published data only}
Crousier 2008 {published data only}
  • Crousier M, Cognet V, Khaled M, Gueugniaud PY, Piriou V. Effect of ketamine on prevention of postmastectomy chronic pain. A pilot study [Effet de la ketamine dans la prevention des douleurs chroniques post-mastectomies. Etude pilote]. Annales Francaises d'Anesthesie et de Reanimation 2008;27(12):987-93. [PUBMED: 19027263]
De Kock 2001 {published data only}
Duale 2009 {published data only}
Dullenkopf 2009 {published data only}
  • Dullenkopf A, Muller R, Dillmann F, Wiedemeier P, Hegi TR, Gautschi S. An intraoperative pre-incision single dose of intravenous ketamine does not have an effect on postoperative analgesic requirements under clinical conditions. Anaesthesia and Intensive Care 2009;37(5):753-7. [PUBMED: 19775039]
Eisenberg 2007 {published data only}
  • Eisenberg E, Pud D, Koltun L, Loven D. Effect of early administration of the N-methyl-d-aspartate receptor antagonist amantadine on the development of postmastectomy pain syndrome: a prospective pilot study. The Journal of Pain 2007;8(3):223-9. [PUBMED: 16996315]
Fassoulaki 2001 {published data only}
  • Fassoulaki A, Sarantopoulos C, Melemeni A, Hogan Q. Regional block and mexiletine: the effect on pain after cancer breast surgery. Regional Anesthesia and Pain Medicine 2001;26(3):223-8. [PUBMED: 11359221]
Fassoulaki 2002 {published data only}
  • Fassoulaki A, Patris K, Sarantopoulos C, Hogan Q. The analgesic effect of gabapentin and mexiletine after breast surgery for cancer. Anesthesia and Analgesia 2002;95(4):985-91, table of contents. [PUBMED: 12351281]
Fransen 2006 {published data only}
  • Fransen M, Anderson C, Douglas J, MacMahon S, Neal B, Norton R, et al. Safety and efficacy of routine postoperative ibuprofen for pain and disability related to ectopic bone formation after hip replacement surgery (HIPAID): randomised controlled trial. BMJ (Clinical research ed.) 2006;333(7567):519. [PUBMED: 16885182]
Gianesello 2012 {published data only}
  • Gianesello L, Pavoni V, Barboni E, Galeotti I, Nella A. Perioperative pregabalin for postoperative pain control and quality of life after major spinal surgery. Journal of Neurosurgical Anesthesiology 2012;24(2):121-6. [PUBMED: 22045156]
Grigoras 2012 {published data only}
  • Grigoras A, Lee P, Sattar F, Shorten G. Perioperative intravenous lidocaine decreases the incidence of persistent pain after breast surgery. The Clinical Journal of Pain 2012;28(7):567-72. [PUBMED: 22699129]
Hayes 2004 {published data only}
  • Hayes C, Armstrong-Brown A, Burstal R. Perioperative intravenous ketamine infusion for the prevention of persistent post-amputation pain: a randomized, controlled trial. Anaesthesia and Intensive Care 2004;32(3):330-8. [PUBMED: 15264726]
Ilkjaer 2000 {published data only}
  • Ilkjaer S, Bach LF, Nielsen PA, Wernberg M, Dahl JB. Effect of preoperative oral dextromethorphan on immediate and late postoperative pain and hyperalgesia after total abdominal hysterectomy. Pain 2000;86(1-2):19-24. [PUBMED: 10779656]
Karanikolas 2011 {published data only}
  • Karanikolas M, Aretha D, Tsolakis I, Monantera G, Kiekkas P, Papadoulas S, et al. Optimized perioperative analgesia reduces chronic phantom limb pain intensity, prevalence, and frequency: a prospective, randomized, clinical trial. Anesthesiology 2011;114(5):1144-54. [PUBMED: 21368651]
Katz 2004a {published data only}
  • Katz J, Schmid R, Snijdelaar DG, Coderre TJ, McCartney CJ, Wowk A. Pre-emptive analgesia using intravenous fentanyl plus low-dose ketamine for radical prostatectomy under general anesthesia does not produce short-term or long-term reductions in pain or analgesic use. Pain 2004;110(3):707-18. [PUBMED: 15288412]
Kim 2010 {published data only}
  • Kim SY, Jeong JJ, Chung WY, Kim HJ, Nam KH, Shim YH. Perioperative administration of pregabalin for pain after robot-assisted endoscopic thyroidectomy: a randomized clinical trial. Surgical Endoscopy 2010;24(11):2776-81. [PUBMED: 20376496]
Kinney 2011 {published data only}
Lakdja 1997 {published data only}
  • Lakdja F, Dixmerias F, Bussieres E, Fonrouge JM, Lobera A. Preventive analgesic effect of intraoperative administration of ibuprofen-arginine on postmastectomy pain syndrome [Effet analgesique preventif d'une administration perioperatoire d'ibuprofene-arginine sur le syndrome douloureux postmastectomie]. Bulletin du Cancer 1997;84(3):259-63. [PUBMED: 9207871]
Malek 2006 {published data only}
  • Malek J, Kurzova A, Bendova M, Noskova P, Strunova M, Vedral T. The prospective study on the effect of a preemptive long-term postoperative administration of a low-dose ketamine on the incidence of chronic post-mastectomy pain. [Efekt perioperacniho podavani ketaminu na potlaceni vzniku chronicke bolesti po operaci prsu - prospektivni studie]. Anesteziologie a Intenzivni Medicina 2006;17(1):34-37.
Moore 2011 {published data only}
  • Moore A, Costello J, Wieczorek P, Shah V, Taddio A, Carvalho JC. Gabapentin improves postcesarean delivery pain management: a randomized, placebo-controlled trial. Anesthesia and Analgesia 2011;112(1):167-73. [PUBMED: 21081764]
Nikolajsen 2006 {published data only}
  • Nikolajsen L, Finnerup NB, Kramp S, Vimtrup AS, Keller J, Jensen TS. A randomized study of the effects of gabapentin on postamputation pain. Anesthesiology 2006;105(5):1008-15. [PUBMED: 17065896]
Perrin 2009 {published data only}
  • Perrin SB, Purcell AN. Intraoperative ketamine may influence persistent pain following knee arthroplasty under combined general and spinal anaesthesia: a pilot study. Anaesthesia and Intensive Care 2009;37(2):248-53. [PUBMED: 19400488]
Pesonen 2011 {published data only}
  • Pesonen A, Suojaranta-Ylinen R, Hammaren E, Kontinen VK, Raivio P, Tarkkila P, et al. Pregabalin has an opioid-sparing effect in elderly patients after cardiac surgery: a randomized placebo-controlled trial. British Journal of Anaesthesia 2011;106(6):873-81. [PUBMED: 21474474]
Remerand 2009 {published data only}
  • Remerand F, Le Tendre C, Baud A, Couvret C, Pourrat X, Favard L, et al. The early and delayed analgesic effects of ketamine after total hip arthroplasty: a prospective, randomized, controlled, double-blind study. Anesthesia and Analgesia 2009;109(6):1963-71. [PUBMED: 19923527]
Romundstad 2006 {published data only}
  • Romundstad L, Breivik H, Roald H, Skolleborg K, Romundstad PR, Stubhaug A. Chronic pain and sensory changes after augmentation mammoplasty: long term effects of preincisional administration of methylprednisolone. Pain 2006;124(1-2):92-9. [PUBMED: 16650580]
Schley 2007 {published data only}
Sen 2009 {published data only}
  • Sen H, Sizlan A, Yanarates O, Senol MG, Inangil G, Sucullu I, et al. The effects of gabapentin on acute and chronic pain after inguinal herniorrhaphy. European Journal of Anaesthesiology 2009;26(9):772-6. [PUBMED: 19424073]
Sen 2009a {published data only}
  • Sen H, Sizlan A, Yanarates O, Emirkadi H, Ozkan S, Dagli G, et al. A comparison of gabapentin and ketamine in acute and chronic pain after hysterectomy. Anesthesia and Analgesia 2009;109(5):1645-50. [PUBMED: 19843803]
Spreng 2010 {published data only}
  • Spreng AJ, Dahl V, Raeder J. Effects of perioperative S (+) ketamine infusion added to multimodal analgesia inpatients undergoing ambulatory haemorrhoidectomy. Scandinavian Journal of Pain 2010;1(2):100-5.
Suzuki 2006 {published data only}
  • Suzuki M, Haraguti S, Sugimoto K, Kikutani T, Shimada Y, Sakamoto A. Low-dose intravenous ketamine potentiates epidural analgesia after thoracotomy. Anesthesiology 2006;105(1):111-9. [PUBMED: 16810002]
Sveticic 2008 {published data only}
  • Sveticic G, Farzanegan F, Zmoos P, Zmoos S, Eichenberger U, Curatolo M. Is the combination of morphine with ketamine better than morphine alone for postoperative intravenous patient-controlled analgesia?. Anesthesia and Analgesia 2008;106(1):287-93, table of contents. [PUBMED: 18165592]
Ucak 2011 {published data only}
  • Ucak A, Onan B, Sen H, Selcuk I, Turan A, Yilmaz AT. The effects of gabapentin on acute and chronic postoperative pain after coronary artery bypass graft surgery. Journal of Cardiothoracic and Vascular Anesthesia 2011;25(5):824-9. [PUBMED: 21232979]
Weis 2006 {published data only}
  • Weis F, Kilger E, Roozendaal B, de Quervain DJ, Lamm P, Schmidt M, et al. Stress doses of hydrocortisone reduce chronic stress symptoms and improve health-related quality of life in high-risk patients after cardiac surgery: a randomized study. The Journal of Thoracic and Cardiovascular Surgery 2006;131(2):277-82. [PUBMED: 16434254]

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
Arcioni 2007 {published data only}
  • Arcioni R, Palmisani S, Tigano S, Santorsola C, Sauli V, Romano S, et al. Combined intrathecal and epidural magnesium sulfate supplementation of spinal anesthesia to reduce post-operative analgesic requirements: a prospective, randomized, double-blind, controlled trial in patients undergoing major orthopedic surgery. Acta Anaesthesiologica Scandinavica 2007;51(4):482-9. [PUBMED: 17378788]
Bell 2001 {published data only}
Biyik 2009 {published data only}
  • Biyik I, Gulculer M, Karabiga M, Ergene O, Tayyar N. Efficacy of gabapentin versus diclofenac in the treatment of chest pain and paresthesia in patients with sternotomy. Anadolu Kardiyoloji Dergisi 2009;9(5):390-6. [PUBMED: 19819790]
Bone 2002 {published data only}
  • Bone M, Critchley P, Buggy DJ. Gabapentin in postamputation phantom limb pain: a randomized, double-blind, placebo-controlled, cross-over study. Regional Anesthesia and Pain Medicine 2002;27(5):481-6. [PUBMED: 12373695]
Buvanendran 2003 {published data only}
  • Buvanendran A, Kroin JS, Tuman KJ, Lubenow TR, Elmofty D, Moric M, et al. Effects of perioperative administration of a selective cyclooxygenase 2 inhibitor on pain management and recovery of function after knee replacement: a randomized controlled trial. JAMA 2003;290(18):2411-8. [PUBMED: 14612477]
Camilleri 2001 {published data only}
  • Camilleri M, Chey WY, Mayer EA, Northcutt AR, Heath A, Dukes GE, et al. A randomized controlled clinical trial of the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome. Archives of Internal Medicine 2001;161(14):1733-40. [PUBMED: 11485506]
Capdevila 1999 {published data only}
  • Capdevila X, Barthelet Y, Biboulet P, Ryckwaert Y, Rubenovitch J, d'Athis F. Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology 1999;91(1):8-15. [PUBMED: 10422923]
Chiu 2008 {published data only}
  • Chiu KM, Wu CC, Wang MJ, Lu CW, Shieh JS, Lin TY, et al. Local infusion of bupivacaine combined with intravenous patient-controlled analgesia provides better pain relief than intravenous patient-controlled analgesia alone in patients undergoing minimally invasive cardiac surgery. The Journal of Thoracic and Cardiovascular Surgery 2008;135(6):1348-52. [PUBMED: 18544384]
Clarke 2010 {published data only}
  • Clarke H, Kay J, Mitsakakis N, Katz J. Acute pain after total hip arthroplasty does not predict the development of chronic postsurgical pain 6 months later. Journal of Anesthesia 2010 Aug;24(4):537-43.
Cobellis 2004 {published data only}
  • Cobellis L, Razzi S, De Simone S, Sartini A, Fava A, Danero S, et al. The treatment with a COX-2 specific inhibitor is effective in the management of pain related to endometriosis. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2004;116(1):100-2. [PUBMED: 15294376]
Cohen 2006 {published data only}
  • Cohen SP, Sireci A, Wu CL, Larkin TM, Williams KA, Hurley RW. Pulsed radiofrequency of the dorsal root ganglia is superior to pharmacotherapy or pulsed radiofrequency of the intercostal nerves in the treatment of chronic postsurgical thoracic pain. Pain Physician 2006;9(3):227-35. [PUBMED: 16886031]
Elkaradawy 2012 {published data only}
  • Elkaradawy S, Nasr M, Elkerm Y, El Deeb M, Yassine O. The effect of multimodal balanced anaesthesia and long term gabapentin on neuropathic pain, nitric oxide and interleukin-1β following breast surgery. Egyptian Journal of Anaesthesia 2012;28(1):67-78.
Essving 2009 {published data only}
  • Essving P, Axelsson K, Kjellberg J, Wallgren O, Gupta A, Lundin A. Reduced hospital stay, morphine consumption, and pain intensity with local infiltration analgesia after unicompartmental knee arthroplasty. Acta Orthopaedica 2009;80(2):213-9. [PUBMED: 19404806]
Essving 2010 {published data only}
  • Essving P, Axelsson K, Kjellberg J, Wallgren O, Gupta A, Lundin A. Reduced morphine consumption and pain intensity with local infiltration analgesia (LIA) following total knee arthroplasty. Acta Orthopaedica 2010;81(3):354-60. [PUBMED: 20450425]
Fassoulaki 2000 {published data only}
  • Fassoulaki A, Sarantopoulos C, Melemeni A, Hogan Q. EMLA reduces acute and chronic pain after breast surgery for cancer. Regional Anesthesia and Pain Medicine 2000;25(4):350-5. [PUBMED: 10925929]
Fassoulaki 2005 {published data only}
  • Fassoulaki A, Triga A, Melemeni A, Sarantopoulos C. Multimodal analgesia with gabapentin and local anesthetics prevents acute and chronic pain after breast surgery for cancer. Anesthesia and Analgesia 2005;101(5):1427-32. [PUBMED: 16244006]
Fassoulaki 2006 {published data only}
  • Fassoulaki A, Stamatakis E, Petropoulos G, Siafaka I, Hassiakos D, Sarantopoulos C. Gabapentin attenuates late but not acute pain after abdominal hysterectomy. European Journal of Anaesthesiology 2006;23(2):136-41. [PUBMED: 16426468]
Fassoulaki 2007 {published data only}
  • Fassoulaki A, Melemeni A, Stamatakis E, Petropoulos G, Sarantopoulos C. A combination of gabapentin and local anaesthetics attenuates acute and late pain after abdominal hysterectomy. European Journal of Anaesthesiology 2007;24(6):521-8. [PUBMED: 17207299]
Fransen 2004 {published data only}
  • Fransen M. Preventing chronic ectopic bone-related pain and disability after hip replacement surgery with perioperative ibuprofen. A multicenter, randomized, double-blind, placebo-controlled trial (HIPAID). Controlled Clinical Trials 2004;25(2):223-33. [PUBMED: 15020038]
Guan 2005 {published data only}
  • Guan ZP, Feng Y, Lu HS. Effect of perioperative use of selective cyclooxygenase-2 inhibitor on postoperative pain, bleeding volume and functional recovery of the knee joints after joint replacement of both knees. [圍手術期使用選擇性環氧合酶2抑制劑對雙膝關節置換術后疼痛、出血量以及膝關節功能恢復的影響]. Chinese Journal of Clinical Rehabilitation 2005;9(6):4-7.
Gupta 2006 {published data only}
  • Gupta A, Fant F, Axelsson K, Sandblom D, Rykowski J, Johansson JE, et al. Postoperative analgesia after radical retropubic prostatectomy: a double-blind comparison between low thoracic epidural and patient-controlled intravenous analgesia. Anesthesiology 2006;105(4):784-93. [PUBMED: 17006078]
Harding 1991 {published data only}
Hartrick 2011 {published data only}
  • Hartrick CT, Pestano C, Carlson N, Hartrick S. Capsaicin instillation for postoperative pain following total knee arthroplasty: a preliminary report of a randomized, double-blind, parallel-group, placebo-controlled, multicentre trial. Clinical Drug Investigation 2011;31(12):877-82. [PUBMED: 21971213]
Honigmann 2007 {published data only}
  • Honigmann P, Fischer H, Kurmann A, Audige L, Schupfer G, Metzger J. Investigating the effect of intra-operative infiltration with local anaesthesia on the development of chronic postoperative pain after inguinal hernia repair. A randomized placebo controlled triple blinded and group sequential study design [NCT00484731]. BMC Surgery 2007;7:22. [PUBMED: 17986324]
Huse 2001 {published data only}
Jaeger 1992 {published data only}
Jirarattanaphochai 2007 {published data only}
  • Jirarattanaphochai K, Jung S, Thienthong S, Krisanaprakornkit W, Sumananont C. Peridural methylprednisolone and wound infiltration with bupivacaine for postoperative pain control after posterior lumbar spine surgery: a randomized double-blinded placebo-controlled trial. Spine 2007;32(6):609-16; discussion 617. [PUBMED: 17413463]
Kadic 2009 {published data only}
Kamencic 2008 {published data only}
  • Kamencic H, Thiel JA. Pentoxifylline after conservative surgery for endometriosis: a randomized, controlled trial. Journal of Minimally Invasive Gynecology 2008;15(1):62-6. [PUBMED: 18262146]
Kampe 2003 {published data only}
  • Kampe S, Kiencke P, Delis A, Auweiler M, Konig DP, Kasper SM. The continuous epidural infusion of ropivacaine 0.1% with 0.5 microg x mL(-1) sufentanil provides effective postoperative analgesia after total hip replacement: a pilot study. Canadian Journal of Anaesthesia = Journal Canadien d'Anesthesie 2003;50(6):580-5. [PUBMED: 12826550]
Katz 2004 {published data only}
  • Katz J, Cohen L. Preventive analgesia is associated with reduced pain disability 3 weeks but not 6 months after major gynecologic surgery by laparotomy. Anesthesiology 2004;101(1):169-74. [PUBMED: 15220787]
Kim 2011 {published data only}
Kollender 2008 {published data only}
  • Kollender Y, Bickels J, Stocki D, Maruoani N, Chazan S, Nirkin A, et al. Subanaesthetic ketamine spares postoperative morphine and controls pain better than standard morphine does alone in orthopaedic-oncological patients. European Journal of Cancer (Oxford, England) 2008;44(7):954-62. [PUBMED: 18396035]
Koninckx 2008 {published data only}
  • Koninckx PR, Craessaerts M, Timmerman D, Cornillie F, Kennedy S. Anti-TNF-alpha treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial. Human Reproduction (Oxford, England) 2008;23(9):2017-23. [PUBMED: 18556683]
Lambert 2001 {published data only}
  • Lambert AW, Dashfield AK, Cosgrove C, Wilkins DC, Walker AJ, Ashley S. Randomized prospective study comparing preoperative epidural and intraoperative perineural analgesia for the prevention of postoperative stump and phantom limb pain following major amputation. Regional Anesthesia and Pain Medicine 2001;26(4):316-21. [PUBMED: 11464349]
Lampl 2002 {published data only}
  • Lampl C, Yazdi K, Roper C. Amitriptyline in the prophylaxis of central poststroke pain. Preliminary results of 39 patients in a placebo-controlled, long-term study. Stroke 2002;33(12):3030-2. [PUBMED: 12468808]
Lavand'homme 2005 {published data only}
  • Lavand'homme P, De Kock M, Waterloos H. Intraoperative epidural analgesia combined with ketamine provides effective preventive analgesia in patients undergoing major digestive surgery. Anesthesiology 2005;103(4):813-20. [PUBMED: 16192774]
Lynch 2003 {published data only}
  • Lynch ME, Clark AJ, Sawynok J. Intravenous adenosine alleviates neuropathic pain: a double blind placebo controlled crossover trial using an enriched enrolment design. Pain 2003;103(1-2):111-7. [PUBMED: 12749965]
Maier 2003 {published data only}
  • Maier C, Dertwinkel R, Mansourian N, Hosbach I, Schwenkreis P, Senne I, et al. Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb pain--results of a randomized double-blinded, placebo-controlled trial. Pain 2003;103(3):277-83. [PUBMED: 12791434]
Martin 2008 {published data only}
  • Martin F, Martinez V, Mazoit JX, Bouhassira D, Cherif K, Gentili ME, et al. Antiinflammatory effect of peripheral nerve blocks after knee surgery: clinical and biologic evaluation. Anesthesiology 2008;109(3):484-90. [PUBMED: 18719447]
Morin 2005 {published data only}
  • Morin AM, Kratz CD, Eberhart LH, Dinges G, Heider E, Schwarz N, et al. Postoperative analgesia and functional recovery after total-knee replacement: comparison of a continuous posterior lumbar plexus (psoas compartment) block, a continuous femoral nerve block, and the combination of a continuous femoral and sciatic nerve block. Regional Anesthesia and Pain Medicine 2005;30(5):434-45. [PUBMED: 16135347]
Nehler 2007 {published data only}
  • Nehler MR, Brass EP, Anthony R, Dormandy J, Jiao J, McNamara TO, et al. Adjunctive parenteral therapy with lipo-ecraprost, a prostaglandin E1 analog, in patients with critical limb ischemia undergoing distal revascularization does not improve 6-month outcomes. Journal of Vascular Surgery 2007;45(5):953-60; discussion 960-1. [PUBMED: 17350216]
Nesher 2008 {published data only}
  • Nesher N, Serovian I, Marouani N, Chazan S, Weinbroum AA. Ketamine spares morphine consumption after transthoracic lung and heart surgery without adverse hemodynamic effects. Pharmacological Research 2008;58(1):38-44. [PUBMED: 18602474]
Nesher 2009 {published data only}
  • Nesher N, Ekstein MP, Paz Y, Marouani N, Chazan S, Weinbroum AA. Morphine with adjuvant ketamine vs higher dose of morphine alone for immediate postthoracotomy analgesia. Chest 2009;136(1):245-52. [PUBMED: 18753471]
Nikolajsen 1997 {published data only}
  • Nikolajsen L, Ilkjaer S, Christensen JH, Kroner K, Jensen TS. Randomised trial of epidural bupivacaine and morphine in prevention of stump and phantom pain in lower-limb amputation. Lancet 1997;350(9088):1353-7. [PUBMED: 9365449]
Nikolajsen 2000 {published data only}
  • Nikolajsen L, Gottrup H, Kristensen AG, Jensen TS. Memantine (a N-methyl-D-aspartate receptor antagonist) in the treatment of neuropathic pain after amputation or surgery: a randomized, double-blinded, cross-over study. Anesthesia and Analgesia 2000;91(4):960-6. [PUBMED: 11004057]
Nissman 2008 {published data only}
  • Nissman SA, Tractenberg RE, Babbar-Goel A, Pasternak JF. Oral gabapentin for the treatment of postoperative pain after photorefractive keratectomy. American Journal of Ophthalmology 2008;145(4):623-9. [PUBMED: 18226799]
Obata 1999 {published data only}
  • Obata H, Saito S, Fujita N, Fuse Y, Ishizaki K, Goto F. Epidural block with mepivacaine before surgery reduces long-term post-thoracotomy pain. Canadian Journal of Anaesthesia = Journal Canadien d'Anesthesie 1999;46(12):1127-32. [PUBMED: 10608205]
Parker 2006 {published data only}
  • Parker JD, Leondires M, Sinaii N, Premkumar A, Nieman LK, Stratton P. Persistence of dysmenorrhea and nonmenstrual pain after optimal endometriosis surgery may indicate adenomyosis. Fertility and Sterility 2006;86(3):711-5. [PUBMED: 16782099]
Perniola 2009 {published data only}
  • Perniola A, Gupta A, Crafoord K, Darvish B, Magnuson A, Axelsson K. Intraabdominal local anaesthetics for postoperative pain relief following abdominal hysterectomy: a randomized, double-blind, dose-finding study. European Journal of Anaesthesiology 2009;26(5):421-9. [PUBMED: 19521298]
Reuben 2004 {published data only}
  • Reuben SS, Makari-Judson G, Lurie SD. Evaluation of efficacy of the perioperative administration of venlafaxine XR in the prevention of postmastectomy pain syndrome. Journal of Pain and Symptom Management 2004;27(2):133-9. [PUBMED: 15157037]
Reuben 2005 {published data only}
  • Reuben S, Gutta SB, Maciolek H, Sklar J, Redford J. Effect of initiating a preventative multimodal analgesic regimen upon long-term patient outcomes after anterior cruciate ligament reconstruction for same-day surgery: A 1200-patient case series. Acute Pain 2005;7:65-73.
Reuben 2006 {published data only}
  • Reuben SS, Ekman EF, Raghunathan K, Steinberg RB, Blinder JL, Adesioye J. The effect of cyclooxygenase-2 inhibition on acute and chronic donor-site pain after spinal-fusion surgery. Regional Anesthesia and Pain Medicine 2006;31(1):6-13. [PUBMED: 16418018]
Reuben 2007 {published data only}
  • Reuben SS, Ekman EF. The effect of initiating a preventive multimodal analgesic regimen on long-term patient outcomes for outpatient anterior cruciate ligament reconstruction surgery. Anesthesia and Analgesia 2007;105(1):228-32. [PUBMED: 17578979]
Reuben 2008 {published data only}
  • Reuben SS, Buvenandran A, Katz B, Kroin JS. A prospective randomized trial on the role of perioperative celecoxib administration for total knee arthroplasty: improving clinical outcomes. Anesthesia and Analgesia 2008;106(4):1258-64, table of contents. [PUBMED: 18349203]
Rhodes 1988 {published data only}
Ryu 2011 {published data only}
  • Ryu HG, Lee CJ, Kim YT, Bahk JH. Preemptive low-dose epidural ketamine for preventing chronic postthoracotomy pain: a prospective, double-blinded, randomized, clinical trial. The Clinical Journal of Pain 2011;27(4):304-8. [PUBMED: 21178605]
Salengros 2010 {published data only}
  • Salengros JC, Huybrechts I, Ducart A, Faraoni D, Marsala C, Barvais L, et al. Different anesthetic techniques associated with different incidences of chronic post-thoracotomy pain: low-dose remifentanil plus presurgical epidural analgesia is preferable to high-dose remifentanil with postsurgical epidural analgesia. Journal of Cardiothoracic and Vascular Anesthesia 2010;24(4):608-16. [PUBMED: 20005744]
Sanders 2009 {published data only}
  • Sanders JC, Gerstein N, Torgeson E, Abram S. Intrathecal baclofen for postoperative analgesia after total knee arthroplasty. Journal of Clinical Anesthesia 2009;21(7):486-92. [PUBMED: 20006256]
Senturk 2002 {published data only}
  • Senturk M, Ozcan PE, Talu GK, Kiyan E, Camci E, Ozyalcin S, et al. The effects of three different analgesia techniques on long-term postthoracotomy pain. Anesthesia and Analgesia 2002;94(1):11-5, table of contents. [PUBMED: 11772793]
Sesti 2007 {published data only}
  • Sesti F, Pietropolli A, Capozzolo T, Broccoli P, Pierangeli S, Bollea MR, et al. Hormonal suppression treatment or dietary therapy versus placebo in the control of painful symptoms after conservative surgery for endometriosis stage III-IV. A randomized comparative trial. Fertility and Sterility 2007;88(6):1541-7. [PUBMED: 17434511]
Singh 2007 {published data only}
  • Singh K, Phillips FM, Kuo E, Campbell M. A prospective, randomized, double-blind study of the efficacy of postoperative continuous local anesthetic infusion at the iliac crest bone graft site after posterior spinal arthrodesis: a minimum of 4-year follow-up. Spine 2007;32(25):2790-6. [PUBMED: 18245999]
Solak 2007 {published data only}
  • Solak O, Metin M, Esme H, Solak O, Yaman M, Pekcolaklar A, et al. Effectiveness of gabapentin in the treatment of chronic post-thoracotomy pain. European Journal of Cardio-Thoracic Surgery 2007;32(1):9-12. [PUBMED: 17442584]
Tramer 1996 {published data only}
Wai 2010 {published data only}
  • Wai EK, Sathiaseelan S, O'Neil J, Simchison BL. Local administration of morphine for analgesia after autogenous anterior or posterior iliac crest bone graft harvest for spinal fusion: a prospective, randomized, double-blind, placebo-controlled study. Anesthesia and Analgesia 2010;110(3):928-33. [PUBMED: 20042446]
Waikakul 1999 {published data only}
White 2007 {published data only}
  • White PF, Sacan O, Tufanogullari B, Eng M, Nuangchamnong N, Ogunnaike B. Effect of short-term postoperative celecoxib administration on patient outcome after outpatient laparoscopic surgery. Canadian Journal of Anaesthesia = Journal Canadien d'Anesthesie 2007;54(5):342-8. [PUBMED: 17470884]
Wu 2008 {published data only}
  • Wu CL, Agarwal S, Tella PK, Klick B, Clark MR, Haythornthwaite JA, et al. Morphine versus mexiletine for treatment of postamputation pain: a randomized, placebo-controlled, crossover trial. Anesthesiology 2008;109(2):289-96. [PUBMED: 18648238]

References to studies awaiting assessment

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
Bilgen 2012 {published data only}
  • Bilgen S, Köner O, Türe H, Menda F, Fiçicioğlu C, Aykaç B. Effect of three different doses of ketamine prior to general anaesthesia on postoperative pain following Caesarean delivery: a prospective randomized study.. Minerva Anesthesiology 2012 Apr;78(4):442-9.
Cohen 2013 {published data only}
  • Cohen SP, Galvagno SM, Plunkett A, Harris D, Kurihara C, Turabi A, Rehrig S, Buckenmaier CC 3rd, Chelly JE. A multicenter, randomized, controlled study evaluating preventive etanercept on postoperative pain after inguinal hernia repair.. Anesthesia and Analgesia 2013 Feb;116(2):455-62.
Fassoulaki 2012 {published data only}
  • Fassoulaki A, Melemeni A, Tsaroucha A, Paraskeva A. Perioperative pregabalin for acute and chronic pain after abdominal hysterectomy or myomectomy: a randomised controlled trial.. European Journal of Anaesthesiology 2012 Nov;29(11):531-6.
Martinez 2013 {published data only}
  • Martinez V, Szekely B, Lemarié J, Martin F, Gentili M, Ben Ammar S, Lepeintre  JF, Garreau de Loubresse C, Chauvin M, Bouhassira D, Fletcher D. The efficacy of  a glial inhibitor, minocycline, for preventing persistent pain after lumbar discectomy: A randomized, double-blind, controlled study.. Pain. 2013 Aug;154(8):1197-203.
Mendola 2012 {published data only}
  • Mendola C, Cammarota G, Netto R, Cecci G, Pisterna A, Ferrante D, Casadio C, Della Corte F. S+ -ketamine for control of perioperative pain and prevention of post thoracotomy pain syndrome: a randomized, double-blind study.. Minerva Anesthesiology 2012 Jul;78(7):757-66.
NCT00224588 {unpublished data only}


Short 2012 {published data only}
  • Short J, Downey K, Bernstein P, Shah V, Carvalho JC. A single preoperative dose of gabapentin does not improve postcesarean delivery pain management: a randomized, double-blind, placebo-controlled dose-finding trial.. Anesthesia and Analgesia 2012 Dec;115(6):1336-42.

References to ongoing studies

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
NCT00129597 {unpublished data only}
  • Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy. Ongoing study December 2004.
NCT00442546 {unpublished data only}
  • Efficacy And Safety Of Pregabalin For Pain Following Total Knee Replacement. Ongoing study May 2007.
NCT00468845 {unpublished data only}
  • Study Of The Efficacy And Safety Of Pregabalin Compared To Placebo For Treatment Of Post-Surgical Pain From Hysterectomy. Ongoing study June 2007.
NCT00551135 {unpublished data only}
  • Surgical Pain After Inguinal Hernia Repair (SPAIHR). Ongoing study January 2008.
NCT00583869 {unpublished data only}
  • Role of Pregabalin in Treatment of Post-Op Pain in Fracture Patients (LYRICA). Ongoing study May 2007.
NCT00618423 {unpublished data only}
  • The Effect of Perioperative Ketamine on Acute and Chronic Pain After Major Back Surgery (KetaDol). Ongoing study October 2007.
NCT00631891 {unpublished data only}
  • Pregabalin in Treating Pain in Women Undergoing Mastectomy or Lumpectomy. Ongoing study December 2006.
NCT00663962 {unpublished data only}
  • Pregabalin and Post-thoracotomy Pain. Ongoing study April 2008.
NCT00762099 {unpublished data only}
  • Perioperative Pregabalin Use, Rehabilitation, Pain Outcomes and Anxiety Following Hip Surgery (RCT). Ongoing study May 2009.
NCT00852683 {unpublished data only}
  • The Effects of Peri-Operative Pregabalin on Post-Operative Pain Following Breast Cancer Surgery With Axillary Node Dissection: A Pilot Study. Ongoing study May 2008.
NCT00905437 {unpublished data only}
  • Study To Investigate The Effectiveness Of Pregabalin For Management Of Patients Undergoing Total Hip Replacement. Ongoing study November 2009.
NCT00967135 {unpublished data only}
  • Efficacy of Perioperative Pregabalin in Reducing the Incidence of Chronic Neuropathic Pain and Postthoracotomy Syndrome.. Ongoing study June 2010.
NCT01022840 {unpublished data only}
  • The Preemptive Analgetic Potency of Low Dose S-Ketamine (Miniket). Ongoing study February 2009.
NCT01116583 {unpublished data only}
  • The Effect of Gabapentin on Thoracic Epidural Analgesia Following Thoracotomy (GABATEA). Ongoing study May 2011.
NCT01204242 {unpublished data only}
  • IV Lidocaine for Patients Undergoing Primary Breast Cancer Surgery: Effects on Postoperative Recovery and Cancer. Ongoing study August 2009.
NCT01243801 {unpublished data only}
  • Prevention of Persistent Postsurgical Pain After Thoracotomy. Ongoing study September 2008.
NCT01296347 {unpublished data only}
  • Low Dose Peri-operative IV Ketamine for Chronic Post-surgery Pain Prevention. Ongoing study April 2011.
NCT01359059 {unpublished data only}
  • Pre- Versus Post-incisional Pregabalin for Postoperative Pain Attenuation and Analgesics Spare in Orthopedic Oncologic Patients. Ongoing study June 2011.
NCT01391858 {unpublished data only}
  • Postoperative Pain and Morphine Consumption After Mastectomy - Lyrica. Ongoing study December 2006.
NCT01480765 {unpublished data only}
  • Preventing Pain After Heart Surgery. Ongoing study November 2011.

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
Andreae 2008
  • Andreae MH, Andreae DA, Motschall E, Rücker G, Timmer A. Local anaesthetics and regional anaesthesia for preventing chronic pain after surgery. Cochrane Database of Systematic Reviews 2008, Issue 2. [DOI: 10.1002/14651858.CD007105]
Bhandari 2005
Burton 1999
  • Burton AW, Lee DH, Saab C, Chung JM. Preemptive intrathecal ketamine injection produces a long-lasting decrease in neuropathic pain behaviors in a rat model. Regional Anesthesia and Acute Pain Management 1999;24(3):208-13.
Cesena 1999
Clarke 2012
  • Clarke H, Bonin RP, Orser BA, Englesakis M, Wijeysundera DN, Katz J. The prevention of chronic postsurgical pain using gabapentin and pregabalin: a combined systematic review and meta-analysis. Anesthesia and analgesia 2012;115(2):428-42. [PUBMED: 22415535]
Crombie 1998
D'Mello 2008
Dahl 2011
Dworkin 2005
  • Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain 2005;113(1-2):9-19. [PUBMED: 15621359]
Dworkin 2010
  • Dworkin RH, McDermott MP, Raja SN. Preventing chronic postsurgical pain: how much of a difference makes a difference?. Anesthesiology 2010; Vol. 112, issue 3:516-8. [PUBMED: 20124976]
Higgins 2011
  • Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ (Clinical research ed.) 2011;343:d5928. [PUBMED: 22008217]
Katz 2009
  • Katz J, Seltzer Z. Transition from acute to chronic postsurgical pain: risk factors and protective factors. Expert Review of Neurotherapeutics 2009;9(5):723-44. [PUBMED: 19402781]
Kehlet 2006
Kehlet 2010
  • Kehlet H, Rathmell JP. Persistent postsurgical pain: the path forward through better design of clinical studies. Anesthesiology 2010; Vol. 112, issue 3:514-5. [PUBMED: 20124977]
McCarson 2005
  • McCarson KE, Ralya A, Reisman SA, Enna SJ. Amitriptyline prevents thermal hyperalgesia and modifications in rat spinal cord GABA(B) receptor expression and function in an animal model of neuropathic pain. Biochemical Pharmacology 2005;71(1-2):196-202.
Moore 1998
  • Moore RA, Gavaghan D, Tramer MR, Collins SL, McQuay HJ. Size is everything--large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects. Pain 1998;78(3):209-16. [PUBMED: 9870574]
Nuesch 2010
  • Nüesch E, Trelle S, Reichenbach S, Rutjes AW, Tschannen B, Altman DG, Egger M, Jüni P. Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study.. BMJ 2010 Jul 16;341. PubMed PMID: 20639294; PubMed Central PMCID: PMC2905513.(c3515):doi: 10.1136/bmj.c3515.
Perkins 2000
Rappaport 2010
  • Rappaport BA, Cerny I, Sanhai WR. ACTION on the prevention of chronic pain after surgery: public-private partnerships, the future of analgesic drug development. Anesthesiology 2010; Vol. 112, issue 3:509-10. [PUBMED: 20124974]
Wen 2007
  • Wen YR, Suter MR, Kawasaki Y, Huang J, Pertin M, Kohno T, et al. Nerve conduction blockade in the sciatic nerve prevents but does not reverse the activation of p38 mitogen-activated protein kinase in spinal microglia in the rat spared nerve injury model. Anesthesiology 2007;107(2):312-21.
Woolf 1991
  • Woolf CJ, Thompson SW. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain 1991;44(3):293-9.
Woolf 2000