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Monday, March 21, 2011
Anesthesia Literature Review: pain. Advance look for May
The following is part of what will appear in the Anesthesia Literature Review, part of the education section that will be found in the May issue of Anesthesiology. Timothy J. Brennan, Ph.D., M.D., is the editor both of the literature review and the pain medicine section which appears below.

Associations between pain and current smoking status among cancer patients. Pain 2011; 152: 60–5

Pain and smoking among cancer patients: The relationship is complex but the clinical implication is clear. Pain 2011; 152:10–1

Previous studies have demonstrated an association between smoking and reduced treatment outcomes; exacerbated symptoms, including pain; and poorer survival in patients with cancer. A cross-sectional study was conducted to examine associations between pain outcomes among cancer patients (N=224) with varied smoking status.

Most patients (68%) had either breast or lung cancer, and all patients were fairly evenly distributed across disease stages. Pain severity was significantly different between never, former, and current smokers (P 0.05), with current and former smokers experiencing more severe pain than never smokers. Among former smokers, an inverse relationship was observed between pain severity and pain interference and the number of years since quitting, regardless of cancer type. Differences were not observed among groups for pain-related distress. No correlation was found between the number of cigarettes smoked per day and pain severity, interference, or related distress.

This study demonstrated a relationship between smoking and nonsmoking and pain, along with a relation between time since quitting and pain in patients with cancer. These data support previous studies suggesting that smoking status is positively associated with other chronic pain syndromes. The accompanying editorial suggests that aggressive promotion of smoking cessation in patients with cancer diagnoses may improve pain management.

The comparative safety of opioids for nonmalignant pain in older adults. Arch Intern Med 2010; 170:1979–86

The comparative safety of analgesics in older adults with arthritis. Arch Intern Med 2010; 170: 1968–76

The safety of opioid analgesics in the elderly: New data raise new concerns. Arch Intern Med 2010; 170:1986–8

There is a dearth of information regarding the comparative safety of nonsteroidal antiinflammatory drugs (NSAIDs) and opioids. Therefore, an observational study with propensity score matching comparing the safety of opioid therapy for nonmalignant pain in older adults was conducted. In addition, a retrospective review of Medicare beneficiaries was performed to compare the safety of nonselective NSAIDs, cyclooxygenase-2 inhibitors, and opioids in elderly patients with osteoarthritis or rheumatoid arthritis. In the first study, all-cause 30-day mortality was increased in users of certain opioids; oxycodone and codeine carried greater risk. The risks of cardiovascular events, fracture, and gastrointestinal events differed between opioid groups and time points (see figs. A and B below for the 30- and 180-day points, respectively).

figure 1

In the second study, all-cause mortality was higher among opioids users (hazard ratio, 1.87) compared with NSAID users. Compared with NSAIDs, opioids were associated with increased risk of cardiovascular events, fracture, and hospitalized safety event (table).

Safety Events per 1,000 Person-Years





CV events








GI Tract Bleeding




Hospitalized SE




The numbers indicate incidence rate.
* Increased risk compared with NSAIDs; † decreased risk compared with NSAIDs.
Coxib=cyclooxygenase-2 inhibitor; CV=cardiovascular; GI=gastrointestinal; NSAID=nonsteroidal antiinflammatory drug; SE=safety event.

These data challenge the concept that opioids may be safer in the elderly population with chronic pain. The accompanying editorial notes the limitations of such retrospective studies; however, the compelling association of increases in fractures in elderly patients prescribed opioids may be related to hormone suppression. Differences among opioids require further evaluation.

Placebos without deception: A randomized controlled trial in irritable bowel syndrome. PLoS One 2010; 5:e15591

Numerous studies have demonstrated the benefit of placebo treatments on both subjective and physiologic outcomes in multiple diseases, including irritable bowel syndrome. The current study assessed the effectiveness of an open-label placebo versus no treatment in patients (N=80) with irritable bowel syndrome in a 3-week randomized controlled trial. Before randomization, patients were told that the placebo pills were inactive or “sugar pills.” At both the 11- and 21-day points, patients in the open-placebo group showed significant improvement in nearly all outcomes compared with the no-treatment group (table).

Placebo versus No Treatment in Patients with Irritable Bowel Syndrome


At 11 days

At 21 days

Global improvement

< 0.001


Adequate relief



Symptom severity reduction



Quality of life improvement



Numbers indicate p value

This trial demonstrated beneficial outcomes of open-label placebo administration in patients with irritable bowel syndrome. The studies suggest that, for patients with diagnoses that are treated almost entirely based on subjective symptoms, the placebo effect can be strong. This may apply to some chronic pain syndromes as well.

Tim Brennan
Dr. Tim Brennan, Assistant Editor-In-Chief for Anesthesiology

We welcome your comments!
About the Author

J. Lance Lichtor, M.D
J. Lance Lichtor, M.D. is a professor of anesthesiology and pediatrics at The University of Massachusetts Medical School. He is the web editor and an associate editor for Anesthesiology.

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