Racial Differences in Placebo Hypoalgesia

Placebo hypoalgesia is a phenomenon where people feel less sensitive to pain after receiving an inert (fake) treatment. Among other things, this phenomenon is the result of believing or expecting relief to occur. It’s a fascinating phenomenon, however there’s more to learn: it’s not currently known whether people of different races experience placebo hypoalgesia in the same way.

New research led by joint first authors Chika Okusogu and Yang Wang from the University of Baltimore, USA, shows that different races experience placebo hypoalgesia differently, using an experimental technique involving manipulating expectations relating to a painful event. The researchers found that self-identifying White individuals reported greater placebo effects compared to African American individuals.

The researchers identified that these racial effects also occurred in patients with chronic pain, albeit to a lesser and more temporary extent.

“We know that minority patients, particularly African Americans, tend to have higher levels of disability when they have pain,” said Roger Fillingim, a pain researcher at the University of Florida, Gainesville. “It is important to understand both pain sensitivity in general but also some of the internal pain modulatory processes as that might help us understand some of the disparities that have been observed in the clinic.”

Fillingim has extensive experience in researching whether people from different ethnic and racial groups experience pain differently, but was not part of the current study.

The study appeared in the August 2020 issue of PAIN.

Right Place, Right Time

For several years, Luana Colloca’s lab has explored the mechanisms underlying placebo effects – the term for the beneficial effects of a sham treatment, attributed to our beliefs in the treatment. To continue this line of research, Colloca had received funding from the National Institute of Dental and Craniofacial Research to explore how genetics, emotions, and our brains are associated with chronic pain that affects our mouth and face. The current study wasn’t the original aim of the grant, she explained.

“[Joint first author] Chika [Okusogu] is a student who won a fellowship from the state of Maryland to rotate through my lab for one summer. He had a huge interest in racial disparities and with his knowledge of these differences in healthcare we quickly decided that this would be the project for the fellowship.”

Okugosa became interested in researching the area through his own experiences as a nursing student, particularly how intimate patient and clinical relationships can be. “As a nurse, you’re working with patients for potentially 12 hours a day. Or, if they are a long-term patient in the ICU, for potentially weeks or months. The therapies we give to patients – [regardless] of whether they are opioids, other analgesics, or massage therapy – are constantly being influenced and changed based on what surrounds the patient, and their past experiences with health care.”

While studying racial differences in placebo effects was not the original goal, being in Baltimore gave Colloca’s laboratory a unique opportunity to undertake this kind of research: two-thirds of the city’s population are African American. Colloca had hoped to undertake this kind of research for several years, but needed enough funding to make the most of the environment her laboratory was situated in.

Previous studies have revealed that racial groups differ in how they experience clinical and experimental pain. These differences have been attributed to genetics, emotions, and cultural factors. Previous research has also shown that people with chronic pain – pain that persists for more than three months – may impair mechanisms that influence how we perceive and react to pain, such as the placebo effect.

However, Fillingim said little research has focused in racial differences on placebo hypoalgesia and other aspects of pain experience. “Other forms of endogenous analgesia have been examined in terms of race group differences, most notably conditioned pain modulation, but I’m not aware of previous studies that have looked at placebo effects across race groups.”

Manipulating the mind

The researchers recruited 60 African Americans and 126 White individuals with pain in the jaw and surrounding muscles – a condition known as chronic temporomandibular disorder. They also recruited 186 pain-free individuals matched for race, sex, and age. The researchers then investigated the association between chronic pain and race using a well-established method of eliciting placebo effects. This method involves two key steps: conditioning and testing.

Placebo hypoalgesia was elicited by a mixture of conditioning (think Pavlov’s dogs) and verbal expectations. A small, computer-controlled device (like a small hotplate from a stove) and an electrical probe were placed on the participant’s arm while they sat in front of a computer screen.

The participants were conditioned to believe that when the computer screen was green, the hotplate would heat up but that the electrical probe would deliver a small shock to counteract the pain caused by the hotplate. They were also conditioned to believe that when the screen was red the electrical probe would be turned off, meaning they would not get any relief from the pain caused by the hotplate.

As a result, the participants learned to associate pain relief with the green screen and the small electric shock. However, the electrical probe was fake and had no effect on the experiment. Unbeknownst to participants, the researchers changed the temperature of the hotplate depending on the colour of the computer screen. Manipulating beliefs and expectations through deception is often a key part of placebo studies.

Once the conditioning phase was complete, the testing phase began. During the testing phase participants were again shown a series of red or green screens. Unlike the conditioning phase, the hotplate always reached the same temperature regardless of the colour of the screen.

A series of ratings were collected from participants including the level of expected pain relief before the conditioning phase, the reinforced expectations of pain relief immediately after the conditioning phase, and ratings of how intense the pain from the hotplate was during the conditioning and testing phases. These ratings were analysed to assess differences between the different racial groups as well as the people with and without chronic pain.

The importance of clinical interactions

After controlling for important factors including age and gender, White participants showed greater placebo effects compared to African American participants. That is, White participants reported a greater reduction in the pain felt by the hotplate when the green screen was presented.

Interestingly, these race effects could be explained by the strength of the conditioning, but not reinforced expectations. This finding suggests that prior expectations – the beliefs that we normally have, prior to any experimental manipulations – are extremely important to placebo effects.

The effects of race on placebo analgesia extended beyond just the participants. “We found interactions between participant race and experimenter race,” explained Wang. Participants with chronic pain reported greater placebo hypoalgesia if the experimenter running the session was the same race, compared to when the participant and experimenter were difference races.

These findings have important clinical implications, according to Fillingim. “The results suggest that if we adequately engage pain inhibitory systems in African Americans, they work every bit as well as in non-Hispanic Whites. If you think about how healthcare gets delivered, it occurs in the course of an interpersonal interaction and there are many more non-minority providers than minority providers.

“Are we interacting with our minority patients in a way that would optimise their expectations of getting better?”

As for future research, the team want to investigate the specific mechanisms that underlie the racial differences for placebo analgesia and pain. “The approaches we have been using for placebo effects – looking at the mechanisms, ranging from pharmacological manipulations to brain imaging – should also be applied to race differences,” Colloca said.

Fillingim agrees that using imaging would be of great value. “Is placebo analgesia mediated by the same brain networks in different racial and ethnic groups? I think that’s a very interesting question, and there are ways to try and optimise engagement of these pain control systems.”

While Okusogu knows investigating the mechanisms underlying these effects is important, he has his own aspirations for this line of research.

“I would love to see if we can manipulate placebo effects in high stress situations. I’m currently working in the emergency department (ED), and pain is by far the most common reason why people are coming in. Can we influence how effective treatments are in an ED setting?”

REFERENCES Okusogu C, Wang Y, Akintola T, Haycock NR, Raghuraman N, Greenspan JD, Phillips J, Dorsey SG, Campbell CM, Colloca L. Placebo hypoalgesia: Racial differences. PAIN. Volume 161, Issue 8, August 2020, Pages 1872-1883