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  • Michele Curatolo

Placebo for pain: from enemy to friend

Updated: Nov 20, 2022


What is the woman in the picture thinking while taking her medication? What are her hopes, fears and expectations? One would wonder why this is important at all. Ultimately, isn't the medication supposed to either work or not, independent of patient thoughts? According to science, the answer is no.

Let's consider the example of a common medication that is prescribed for pain management: duloxetine. Studies have shown that patients with different pain conditions, such as "nerve pain" or low back pain, experience pain relief when taking duloxetine.

According to the rules of evidence-based medicine, a treatment is "efficacious" when pain relief results from a "specific" effect of that treatment; namely, the duloxetine will bind to cells and neural pathways that are involved in pain perception, thus providing pain relief. However, treatments work also because of "unspecific" effects. Providing an unspecific effect is the job of placebo.

The placebo effect relies on the patient’s expectations that a treatment will work.

A patient may experience pain relief from duloxetine (or any other treatment) because of the expectation that the medication will help, and not (or not only) because of the specific effect of duloxetine on pain cells and pathways.

The placebo revolution

Placebo research has brought a revolution in the way we see how pain and pain treatment work. Not so long ago, patients experiencing a placebo effect, namely pain relief with a treatment that is not efficacious per se, were stigmatized. Some practitioners even believed (and may still believe) that this was a sign for "made-up" pain, or "pain all in the head".

Extensive research has demonstrated that a positive patient's expectation activates pathways in the central nervous system that produce pain relief. For instance, opioid-similar substances called endorphins are released in the brain; brain areas that reduce the pain are activated; and pathways that connect these areas to the spinal cord increase their activity and attenuate pain signals arising from an injured area (learn more here (1)).

The placebo effect may be even stronger than the specific effect of the treatment. Let's go back to the example of duloxetine. A study comparing duloxetine with placebo (2) for low back pain found duloxetine to produce more pain relief than placebo. This establishes a "specific" effect of duloxetine. However, looking at the figure below, patients taking only a placebo had significant pain relief, and duloxetine enhanced that effect only to a moderate extent. The ultimate effect of duloxetine, and of any treatment, is the sum of the specific and unspecific effect.

Duloxetine is superior to placebo for low back pain, but the difference is modest.
Duloxetine is superior to placebo for low back pain, but the difference is modest. From Skljarevski et al (2010), J Pain, 11, 1282-1290

Thanks to this research, the placebo effect is now our friend.

A questions for health care professionals

You can choose between two treatments:

  • Treatment A has been shown to be superior to placebo;

  • Treatment B did not undergo placebo-controlled studies, but follow-up studies have shown reduction of pain after the treatment.

You discuss with the patient the two options, and your patient prefers the latter one because they are convinced that it will work better. The risks are comparable.

Here is your choice:

  1. You try to convince the patient that they should go for option A, because it is supported by high evidence of efficacy, whereas treatment B is not.

  2. You support patient's preference and prioritize option B.

I go for option B because I predict a better outcome.

Take-home messages

  • The placebo effect is a physiological response that contributes substantially to pain relief.

  • Observing or suspecting a placebo effect is not a sign that the pain "is not real". Such misconceptions are unfortunately still common among health care professionals and have no scientific foundation.

  • Treatment options should be discussed with patients; inquiring about and taking into consideration patient' expectations increase the chances of treatment success.

Disclosure: This blog has been inspired by the work of the most prominent lab for placebo research, led by Luana Colloca.


  1. Colloca, L., & Barsky, A.J. (2020). Placebo and Nocebo Effects. New England Journal of Medicine, 382, 554-561. 10.1056/NEJMra1907805

  2. Skljarevski, V., Zhang, S., Desaiah, D., Alaka, K.J., Palacios, S., Miazgowski, T., & Patrick, K. (2010). Duloxetine versus placebo in patients with chronic low back pain: a 12-week, fixed-dose, randomized, double-blind trial. The Journal of Pain, 11, 1282-1290. 10.1016/j.jpain.2010.03.002

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