08.04.2013

by Sarah Wickline
Contributing Writer, MedPage Today

• Action Points
  Cues and associations given to people affected their responses to placebos and active treatments in a crossover trial, suggesting that the placebo effect depends more on “state” than “trait”.
• The results imply that the non-specific effects of acupuncture may contribute to the analgesic effect observed in genuine acupuncture analgesia.

Cues and associations given to people affected their responses to placebos and active treatments in a crossover trial, suggesting that the placebo effect depends more on “state” than “trait,” researchers said.

Compared with no treatment, healthy volunteers who received placebo pills or genuine acupuncture both showed significantly increased pain thresholds in average, whereas sham acupuncture did not, according to Jian Kong, MD, MPH, of Massachusetts General Hospital in Boston, and colleagues.

But sham acupuncture — and not placebo pills — correlated significantly with responses to genuine acupuncture, the researchers reported in PLoS ONE.

With placebo responses, “trait” may take a backseat to “state” in a clinical setting, they suggested, with patients’ expectations as conditioned by circumstances of the particular pain-relief intervention dictating their responses.

The study involved 71 healthy, acupuncture-naïve individuals, ages 21 to 37, recruited for two experiments.

In the first, participants were split into four groups: treatment with manual acupuncture, electro-acupuncture, a drug they were told was acetaminophen (Tylenol), or rest. Each participant was given one of the four treatments followed by pain stimulation and verbal suggestion of positive effect.

Over the course of four sessions, each participant was rotated through all four experiment conditions.

Kong and colleagues used a heated probe to gauge pain threshold and tolerance on the right hand and forearm, with two levels of pain stimulation, high and low.

The manual acupuncture was really sham. Needle placement was conducted with the Streitberger sham acupuncture device that looked and felt like acupuncture. The needles did not actually penetrate the skin, nor were they placed along the proper meridians for pain treatment.

All of the “acetaminophen” pills were actually placebo. The people in the rest arm were informed that they were part of the control group and should expect no pain relief. The only actual pain treatment was the electro-acupuncture treatment.

Participants completed a Life Orientation Test to assess general optimism versus pessimism. They were also asked to rate their expectations for pain relief for each condition of the experiment on a 10-point scale.

When in the “acetaminophen” pill group, participants ingested their dose roughly half an hour before the pain stimulation. Acupuncture needles were placed into two points on the right hand and each session lasted for 25 minutes prior to the pain stimulation.

The results of the pre-treatment and post-treatment pain threshold tests showed that genuine acupuncture and placebo pills both produced increases in post-treatment pain threshold (0.79, 95% CI 0.25-1.33, P=0.004, and 0.74, 95% CI 0.19-1.29, P=0.008, respectively).

On a scale from 0-20, participants reported pre- and post-treatment pain levels as follows:

• Electro-acupuncture: pre high 12.1 (SD 0.4), post high 12.6 (SD 0.4); pre low 4.6 (SD 0.4), post low 4.4 (SD 0.4)
• Sham acupuncture: pre high 12.5 (SD 0.5), post high 12.2 (SD 0.6); pre low 4.7 (SD 0.4), post low 4.8 (SD 0.4)
• Placebo pill: pre high 12.2 (SD 0.4), post high 11.8 (SD 0.5); pre low 5.0 (SD 0.4), post low 4.3 (SD 0.4)
• Rest: pre high 12.8 (SD 0.4), post high 12.4 (SD 0.5); pre low 4.8 SD (0.4), post low 4.7 (SD 0.4)

Belief that the placebo pill would do the best job to combat pain ranked highest among participants, followed by acupuncture and then rest (P<0.0001). Participants rated their expectancy for the placebo pill higher than both sham acupuncture (P=0.001) and genuine acupuncture (P=0.003), and also higher than rest (P<0.001).

Kong and colleagues adjusted for age, gender, and scores on the optimism/pessimism scale. In univariate and multivariate analysis, no significant differences were found between post-treatment placebo pill and sham acupuncture pain threshold, (P=0.34 andP=0.40, respectively).

“The results showed that genuine acupuncture and placebo pills could significantly increase subjects’ pain threshold compared with rest control condition,” Kong and colleagues concluded.

Overall, 23 people dropped out of the first experiment and only 45 moved on to the second experiment, which began 2 weeks after completion of the first experiment.

For the second experiment, participants underwent functional magnetic resonance imaging (fMRI) while exposed to visual cues and pain stimulation. The cues were simply the words HIGH and LOW, which participants were told would reflect the amount of pain they would experience. In fact, that was not always true — participants were also sometimes given the LOW cue followed by high pain stimulation.

Results from this phase showed mean pain ratings as follows:

Low-cue, low pain: 5.3 (SD 0.3)

Low-cue, high pain: 11.3 (SD 0.4)

High-cue, high pain: 14.2 (SD 0.3)

Kong and colleagues reported that the difference between the low-cue/high pain and high-cue/high pain conditions was highly significant at P<0.0001.

“Many placebo studies show benefits due to increased attention paid to the patient. This study is elegant because it pays attention to the same patients equally. By rotating them through each condition of the experiment, state characteristics wash out leaving just the trait characteristics involved with pain,” Amy Baxter, MD, chief executive of a company called Buzzy4shots.com that sells an over-the-counter pain relief device, told MedPage Today.

“With previous acupuncture trials, pain management efficacy has been significant, but the contribution from placebo effect has been difficult to determine,” said Baxter, who was not involved with the study. “This paper is important in that it casts a different light on not only acupuncture as a pain management tool, but also validates previous effects in studies without such a fastidious placebo design,” Baxter continued.

• Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco

LAST UPDATED 08.05.2013