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02 Nov

The placebo effect is well-known, especially when it comes to clinical trials. Conventionally, patients receive a placebo believing they are getting an active medication and afterward report improved symptoms. But the ethical problem of giving patients a placebo without their knowledge has impeded its use as a treatment method. Until now, that is. A new study[1] has found that patients who knowingly take a placebo for the treatment of chronic low back pain see improvements in both pain and function – which could lead to another avenue of treatment for those battling chronic pain.

Study Overview

The study, titled “Open-Label Placebo Treatment in Chronic Low Back Pain,” was published in the December issue of PAIN, the official journal of the International Association for the Study of Pain.

The authors selected 97 patients (83 of whom completed the trial) with chronic low back pain, who were then examined by a nurse and board certified pain specialist before receiving a brief overview of the placebo effect. The majority of these patients were already undergoing some kind of treatment for their pain, mostly NSAIDs. (Patients taking opioids were not included in the study.)

Some of the patients were instructed to continue with their treatment as usual, while the others were told to add a placebo pill (in a bottle clearly labeled “Placebo”) twice daily to their existing regime. They were instructed not to make any other lifestyle or medication changes during the study. Both groups spent three weeks doing their respective treatments, while monitoring their average, minimum and maximum pain levels, as well as their level of disability. At the end of the trial, the group that did not take placebo was also given the chance to incorporate it into their treatment for three weeks.

Key Findings

At the end of the three weeks, both groups of patients were brought in for an interview, during which they rated their maximum, minimum and usual pain, as well as their back-related dysfunction. Those in the placebo group experienced a 30% reduction in both usual and maximum pain, while those in the normal treatment group only experienced a 9% reduction in usual pain and a 16% reduction in maximum pain.

Similarly, the placebo group saw a 29% drop in pain-related disability, while those in the normal treatment group saw almost no improvement.[2] These results were seen despite the fact that 70% of the placebo group was initially either skeptical of the placebo or didn’t believe it would have much of an effect.

After the normal treatment group was allowed to utilize placebos for three weeks, they also saw significant pain relief (a 29% decrease in maximum pain and a 46% decrease in minimum pain) and an improvement in back-related disability (which decreased by 40%).

Implications for the Future

It’s not entirely clear why placebos produced such staggering pain relief, but the researchers did put forth several theories. The success could be due, in part, to the positive way placebos were introduced to the group. Presenting the experiment to participants in a positive manner – for instance, as a “novel mind-body clinical” option – may have helped curate hope in the participants. For chronic pain patients who often feel hopeless in the face of ineffective treatment options, this may have been enough to convince them to suspend their disbelief, the researchers hypothesize.

The effects could also be attributed to the physical process of taking a pill. Several other studies have recently shown that the ritual aspects related to pill-taking – like opening the bottle and swallowing – may be linked to positive placebo responses.

No matter the reason, what is clear is that many patients currently suffering from chronic low back pain – and possibly other chronic conditions, as well – might benefit from adding a placebo to their treatment plan. While further studies are necessary to determine how best to utilize this new information on the placebo effect  and how it might relate to longer-term relief, these findings do suggest that placebos may eventually become an important component of treatment, reducing the need for other (possibly harmful) types of drugs.

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[1] Carvalho, Cláudia, Joaquim Machado Caetano, Lidia Cunha, Paula Rebouta, Ted J. Kaptchuk, and Irving Kirsch. “Open-Label Placebo Treatment in Chronic Low Back Pain.” PAIN 157, no. 12 (December 2016): 2766–72.

[2] “Study Finds Knowingly Taking Placebo Pills Eases Pain.” October 14, 2016. Accessed November 11, 2016. http://www.bidmc.org/News/PRLandingPage/2016/October/Kaptchuk-placebo-effect.aspx.

02 Nov

The search for new pain-fighting drugs has been a difficult one. For the past 20 years, drug after drug has failed in the clinical trial stage, unsuccessfully addressing the pain they were created to relieve.[1] But a new study released this month may have found the key. It’s called Substance P – and it could mean better pain control in the coming years.

Study Overview

The study, published August 1 in the journal Antioxidants and Redox Signaling, was put together by researchers from China’s Hebei Medical University and the UK’s University of Leeds.[2] The study particularly looked at how this substance – neuropeptide Substance P – acted within nerve cells in lab and animal models.

Substance P is released by your body in response to “noxious stimuli,” or stressors. Although it has already been established that Substance P has “excitatory effects” on the central nervous system, this study sought to better determine its effects on the peripheral nervous system.

The study focused solely on acute pain, but lead researcher, Dr. Nikita Gamper from the University of Leeds, also plans to look at Substance P’s role in chronic pain. This research was sponsored by the UK’s Medical Research Council and China’s National Basic Research Program and National Natural Science Foundation.[1]

Important Findings

The researchers found that Substance P has the opposite effect on the peripheral nervous system than it does on the central nervous system. While in the central nervous system it excites neurons and promotes pain, it can actually work in the peripheral nervous system to make cells less responsive and excitable, thereby decreasing pain sensations. This is what they called the “pain paradox.” While it promotes pain in one area of the nervous system, Substance P acts as a natural painkiller in another.

This explains why many of the drugs created to fight pain ended up failing in clinical trials. Their intent was to suppress Substance P, but in doing so they suppressed it in both the central and peripheral nervous systems. They thus stopped Substance P from acting as a painkiller in the peripheral nervous system, where it would normally influence certain proteins that control the ability of pain-sensing neurons to respond to noxious stimuli.[1]

Implications for the Future

The researchers concluded that this study helps create a better understanding of how the body naturally fights pain. This, in turn, could lead to new drugs, potentially without the negative side effects of current prescription painkillers.[1]

As Dr. Gamper stated in a release regarding the study,1 “If we could develop a drug to mimic the mechanism that Substance P uses, and ensured it couldn’t pass the blood brain barrier into the central nervous system, so was only active within the peripheral nervous system, it’s likely it could suppress pain with limited side effects.”

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[1] " 'Pain Paradox' Discovery Provides Route to New Pain Control Drugs." ScienceDaily.com. July 28, 2016. Accessed August 12, 2016. https://www.sciencedaily.com/releases/2016/07/160728105608.htm

[2] Huang, Dongyang, Sha Huang, Haixia Gao, Yani Liu, Jinlong Qi, Pingping Chen, Caixue Wang, Jason L. Scragg, Alexander Vakurov, Chris Peers, Xiaona Du, Hailin Zhang, and Nikita Gamper. "Redox-Dependent Modulation of T-Type Ca2 Channels in Sensory Neurons Contributes to Acute Anti-Nociceptive Effect of Substance P." Antioxidants & Redox Signaling 25, no. 5 (August 1, 2016): 233-51.

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