A novel molecular mechanism explains why dark-skinned and light-skinned people respond differently to heat and mechanical stimulation, with implications for the clinical treatment of pain after dental procedures, according to researchers at the Bluestone Center for Clinical Research at the New York University College of Dentistry.
“We know that individuals report different levels of pain following the same dental procedure or surgery. Similarly, there are differences across groups reporting pain relief once they have taken the same analgesic medication,” said study leader and Bluestone Center director Brian L. Schmidt, DDS, MD, PhD. “Potentially, skin pigmentation contributes to these differences and might provide an approach for more targeted and personalized pain treatment.”
Cells that determine skin color known as melanocytes produce dopamine, a small molecule that contributes to the skin’s responsiveness to heat and mechanical stimuli. Kentaro Ono, DDS, an associate professor at Kyushu Dental University in Japan and a visiting scientist at Schmidt’s laboratory, used publicly available data to compare mechanical and heat pain sensitivity in groups of people who differed in skin color.
“We sought out additional publicly available data. However, this time we looked at pigmented and unpigmented rodents based on fur color,” Schmidt said. “We were encouraged by our findings. We knew we had to continue to work in the laboratory to look for the mechanism that would explain why skin sensitivity would depend on color.”
The group’s meta-analysis in rodents, and comparison of genomic differences between mouse strains, pointed to a gene called Tyr that controls pigmentation and dopamine synthesis in the skin. They manipulated dopamine levels in the skin and found that dopamine causes increased expression of TRPV1 and decreased expression of Piezo2, which are proteins that are responsible for heat and mechanical sensitivity, respectively.
“Our skin is a sensory organ that gives us information about our environment, such as temperature and pressure. Excessive heat or pressure produces a pain signal that warns us about the dangerous input. Our environmental condition can change our skin’s sensitivity to environmental stimuli under selective pressure,” said Yi Ye, PhD, associate director of clinical research operations at the Bluestone Center and study coauthor.
“Our study shows that people from different ethnic backgrounds sense temperature and pressure differently. For example, sun exposure in people who live close to the equator leads to melanin buildup, which protects them from UV damage, but also makes skin darker. The same skin cell (melanocytes) that produces melanin releases dopamine, which will increase skin’s sensitivity to heat,” Ye said.
“This finding potentially means that in order to adapt to extreme weather conditions like those in the equator, this skin cell has developed a protective mechanism that warns people away from excessive sun exposure,” Ye said.
The study, “Cutaneous Pigmentation Modulates Skin Sensitivity Via Tyrosinase-Dependent Dopaminergic Signaling,” was published by Scientific Reports.