Most patients who undergo major surgery do not receive adequate treatment of their pain. They suffer needlessly because traditional approaches to the management of acute post-operative pain have focused primarily on treating the patient after surgery in an effort to reduce already established pain. It is becoming increasingly clear, however, that the very act of cutting tissue, nerve, and bone may induce long-lasting changes in central neural function that amplify post-operative pain intensity, increase the need for analgesics, and set the stage for the development of chronic, intractable pain. One of the most effective ways to prevent noxious input during surgery from reaching the spinal cord is to administer local anesthetics and opioids via the epidural route before surgery. This preventive approach to the problem of acute post-operative pain has been termed pre-emptive analgesia and its significance lies not only in the obvious immediate benefit of protecting the patient at the time of surgical trauma, but also in the possibility that such pre-treatment will attenuate the development of central sensitization and of potentially detrimental changes in immune function. The proposed study uses a three group, randomized, double-blind, placebo-controlled, cross-over design. Patients undergoing abdominal hysterectomy will receive (1) pre-incisional epidural fentanyl and lidocaine followed by post-incisional epidural saline, (2) pre-incisional epidural saline followed by post-incisional fentanyl and lidocaine, or (3) pre and post-incisional saline via a sham epidural. All patients will receive a general anesthetic. It is hypothesized that, by interrupting the transmission of noxious peri-operative inputs to the spinal cord, the pre-emptive approach will attenuate the development of central sensitization and result in reduced pain and lower requirements for morphine long after the effects of the epidural agents have worn off. This project will also examine physiological mechanisms and psychosocial moderating factors involved in pain and immune function. Finally, the study will assess the effects of pre-operative psychosocial factors on changes in immune function, pain, and post operative adjustment. The broad aim of this intervention is to increase quality of life by decreasing stress, pain, analgesic requirements, and post-operative immune suppression, possibly reducing post-surgical complications due to infections and morphine usage. The anticipated morphine-sparing effect may reduce potential adverse effects, decrease treatment costs, and shorten length of hospital stay.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS035480-01A1
Application #
2038425
Study Section
Behavioral Medicine Study Section (BEM)
Program Officer
Kitt, Cheryl A
Project Start
1997-07-01
Project End
2000-04-30
Budget Start
1997-07-01
Budget End
1998-04-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Toronto General Hospital
Department
Type
DUNS #
City
Toronto
State
Country
Canada
Zip Code
Katz, Joel; Buis, Tom; Cohen, Lorenzo (2008) Locked out and still knocking: predictors of excessive demands for postoperative intravenous patient-controlled analgesia. Can J Anaesth 55:88-99
Cohen, Lorenzo; Fouladi, Rachel T; Katz, Joel (2005) Preoperative coping strategies and distress predict postoperative pain and morphine consumption in women undergoing abdominal gynecologic surgery. J Psychosom Res 58:201-9
Katz, Joel; Cohen, Lorenzo (2004) Preventive analgesia is associated with reduced pain disability 3 weeks but not 6 months after major gynecologic surgery by laparotomy. Anesthesiology 101:169-74
Snijdelaar, Dirk G; Koren, Gideon; Katz, Joel (2004) Effects of perioperative oral amantadine on postoperative pain and morphine consumption in patients after radical prostatectomy: results of a preliminary study. Anesthesiology 100:134-41
Katz, Joel; Cohen, Lorenzo; Schmid, Roger et al. (2003) Postoperative morphine use and hyperalgesia are reduced by preoperative but not intraoperative epidural analgesia: implications for preemptive analgesia and the prevention of central sensitization. Anesthesiology 98:1449-60
Salomons, Timothy V; Wowk, Adarose Ardiel; Fanning, Ann et al. (2002) Factors associated with refusal to enter a clinical trial: epidural anesthesia is a deterrent to participation. Can J Anaesth 49:583-7
Melzack, R; Coderre, T J; Katz, J et al. (2001) Central neuroplasticity and pathological pain. Ann N Y Acad Sci 933:157-74
Gagliese, L; Jackson, M; Ritvo, P et al. (2000) Age is not an impediment to effective use of patient-controlled analgesia by surgical patients. Anesthesiology 93:601-10
Katz, J; Melzack, R (1999) Measurement of pain. Surg Clin North Am 79:231-52
Schmid, R L; Sandler, A N; Katz, J (1999) Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes. Pain 82:111-25