Pain, Depression and Survival
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Am Fam Physician. 1999 Jul 1;60(1):42-43.
Adequate pain relief has an obvious positive effect on a patient's quality of life. However, recent data suggest that pain control also improves morbidity and mortality, that pain relief administered before surgery and during the postoperative period improves clinical outcomes, and that depression, anxiety and poor coping skills are independently associated with mortality and, therefore, are important factors to address.1 Whether the correlation between improved analgesia and increased life expectancy is the result of biomedical or psychosocial factors is unclear. However, several recent studies support the contention that pain causes increased severity of disease and mortality. Therefore, providing pain relief is not only a humane gesture but also a medical necessity.2
For example, a prospective, randomized placebo-controlled study assessed the efficacy of pain relief in patients with unresectable pancreatic cancer.3 A total of 137 patients were randomized and blinded to receive either intraoperative chemical splanchnicectomy with alcohol block or placebo. This simple technique sections the splanchnic nerve innervation to the retroperitoneum. Patients receiving the alcohol block had a significantly reduced mean pain score after two, four and six months of follow-up. These patients also had a reduced need for postoperative opioids and an improvement in mood; they also had a lower incidence of pain at death. More surprisingly, however, patients who received the alcohol block actually lived longer.
A subsequent analysis of these patients explored the association between pain intensity, mood state and survival.1 Patients with more negative mood states had more preoperative and postoperative pain and a greater limitation of activity because of pain than those with less negative mood states as measured on a simple visual analog scale. It is not known whether the patients' mood states were more negative because of pain and immobility, or if a decrease in mood caused an increase in pain. However, it is clear that the removal of the nociceptive stimulus with a celiac plexus block resulted in decreased opiate use, improvement in mood and an increased life expectancy.
Another study examined the psychologic factors that can predict reported pain and survival.4 A total of 358 patients with leukemia and lymphoma who were about to undergo bone marrow transplantation were evaluated for physical functioning and biomedical, psychologic and social parameters. Following the transplantation procedure, patients completed a visual analog scale measuring oral pain daily for 25 days. In addition, opioid use during this time was documented. Once a week, observable transplant-related oral mucositis, reflecting nociception, was documented in a standardized fashion (using a mucositis index). Tissue injury (i.e., biomedical factors) was the factor that most strongly correlated with pain.
However, the strongest psychologic predictor of future post-transplant pain in this study was distress and worry about the upcoming bone marrow transplantation treatment, confirming that mood and pain are inextricably linked.4,5 Analysis of psychologic factors, controlled for biomedical factors, found that relative risk of mortality was increased by more than 100 percent in patients who had somatic symptoms of depression, 94 percent in patients whose coping style did not include seeking support, and 78 percent in patients with severe symptoms of distress before treatment. These data indicate that psychosocial problems are associated with pain and mortality and should be addressed to improve outcome and survival.
Another study, conducted in animals, explored the hypothesis that painful experiences such as surgery can cause a neuroendocrine response that suppresses the immune system and promotes tumor growth.5,6 The study tested the effect of a pre- and postoperative dose of morphine on tumor metastasis in rats. The study compared laparotomy with anesthesia versus anesthesia alone, and morphine versus placebo for pain relief. Five hours after surgery, a mammary adenocarcinoma (MADB106) cell line, which colonizes the lungs, was introduced intravenously.
In the animals undergoing surgery without morphine, retention and colonization of MADB106 cells in the lung were two- to fourfold higher than in rats receiving morphine.5,6 In the anesthesia-only group, morphine had no effect on the metastatic outcomes. These results were replicated seven times, demonstrating convincingly that analgesia reversed the adverse effects of pain on the immune system.
These preliminary studies further support the importance of adequate pain control and of addressing the psychosocial needs of seriously ill patients. Further research is needed to validate the intriguing concept that, compared with postoperative pain control, pre- and intraoperative analgesia may actually lead to reduced morbidity and mortality.
Dr. Staats is the chief of the Division of Pain Medicine in the Department of Anesthesiology and Critical Care Medicine at the Johns Hopkins Hospital, Baltimore, where he is also the director of the Anesthesia Pain Medicine Clinic. He holds associate professorships in the Department of Anesthesiology and Critical Care and the Department of Oncology at Johns Hopkins University School of Medicine.
Address correspondence to Peter Staats, M.D., Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, 550 N. Broadway, Ste. 301, Baltimore, M.D. 21205..
1. Staats PS, Hekmat H, Sauter P, Lillemoe K. The effects of alcohol, negative mood, and postoperative painon life expectancy in patients with pancreatic cancer. Presented at the American Pain Society Annual Meeting, October 1997.
2. Staats PS. The pain-mortality link. In: Payne R, Patt R, Hill CS, eds. Assessment and treatment of cancer pain. Seattle: IASP Press, 1998:145–56.
3. Lillemoe KD, Cameron JL, Kaufman HS, Yeo CJ, Pitt HA, Sauter PK. Chemical splanchnicectomy in patients with unresectable pancreatic cancer: a prospective randomized trail. Ann Surg. 1993;217:447–55.
4. Syrjala KL, Chapko ME. Evidence for a biopsychosocial model of cancer treatment-related pain. Pain. 1995;61:69–79.
5. Page GG, Ben-Eliyahu S, Liebeskind JC. The role of LGL/NK cells in surgery-induced promotion of metastasis and its attenuation by morphine. Brain Behav Immun. 1994;8:241–50.
6. Page GG, Ben-Eliyahu S, Yirmiya R, Liebeskind JC. Morphine attenuates surgery-induced enhancement of metastatic colonization in rats. Pain. 1993;54:21–8.
Copyright © 1999 by the American Academy of Family Physicians.
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