Regenexx Blog
Dr. Chris Centeno

The entire structure of evidence-based medicine rests on the foundation of one idea, the placebo. Meaning that if a placebo treatment is not as powerful as we think, then countless high-level studies are garbage and the bedrock of modern medical science is built on quicksand. Hence, when someone publishes something about how the placebo effect may have its limitations, it should be a big deal.

What Is a Placebo?
A placebo is typically an inert, or inactive, treatment given to subjects to act as a control against an actual treatment. For example, to determine the effects of glucosamine and chondroitin on arthritis in one randomized control trial (RCT), the test group was given glucosamine and/or chondroitin while the control group was given pills that are made to look like the supplements but actually contain no glucosamine or chondroitin (i.e., the placebo). So what are the placebo treatments made from? Typically starch, saline, or some other nonmedicinal, or neutral, substance.

Surgical experiments can also involve placebo, or fake or sham, surgery. For example, one group of participants in a study, the test group, may receive the actual procedure, while a second group, the control group, receive the same approach to the surgery but not the actual surgery. A good example of this is a study I recently shared on vertebroplasty, where the test group received the vertebroplasty (the injection of bone cement into fractured backbones) and the control group only received the same approach with a simulated bone cement injection, but no actual bone cement was used.

You will often see RCTs (randomized controlled trials) described as “blind” or “double-blind,” and this simply means that the participants in either group (single-blind), and often even the investigators (double-blind), have no idea whether they are in the test group or the placebo group. Why? To key is to eliminate any potential bias in the study.

What Is a Placebo Effect?
A placebo effect is the subject’s response to the placebo treatment be it negative or positive. For example, participants who received the sham surgery (the control group) in the vertebroplasty study I mentioned above reported significant relief of their pain, almost as much relief as the vertebroplasty participants (the test group). This would be considered a placebo effect.

While some might be tempted to say the placebo effect must be all in the head, a new study may change this way of thinking. Let’s review.

How the Brain Reacts to Placebo Treatments
The neurologic pain signal (NPS) is a measure of how the brain responds to pain from a stimulus (called nociceptive pain), such as a burn, fracture, wound, and so on. Nociceptors are nerve receptors located throughout the body, and when an injury occurs, these nociceptors relay the information via our nervous system to our brain. Our brain then tells us that burn we received while pulling a casserole out of the oven hurts.

The purpose of the new study was to investigate how the brain processes pain following placebo treatments. The study, an aggregate of 20 studies consisting of over 600 participants, found that while placebo treatments moderately affect the patients’ reports of pain, there was very limited effect to the patients’ neurologic pain signal, or how the brain actually responded to nociceptive pain.

So the placebo effect is not impacting central pain states in the brain. Meaning, the placebo effect is not as powerful as previously reported, as it’s not changing how pain is registered in the brain. This means if there is a “placebo effect” type of response, the impact is likely happening elsewhere, not via the main nociceptor-brain pathway. Where? The answer to that wasn’t within the scope of this study.

The upshot? The concept of a placebo may have its limitations. Meaning, the effect isn’t changing brain activation in ways we would expect. So why the big placebo effect? First, other studies have raised questions about whether the placebo effect is significant. In addition, for some research investigations, it’s more likely the placebo is an actual therapy itself. For example, we’ve seen this in disc studies against things like platelets and stem cells. Here, it’s likely that the saline used in the disc washes away noxious chemicals, so patients report relief. Hence, the placebo effect may not be all we think. Which is a VERY, VERY big deal.