Emily Cai

The Women’s Health Research at Yale, or WHRY, has funded a new study to research sex differences in clinical outcomes for pain treatment and for opioid use disorder treatment.

WHRY funds research on human health as it differs by sex and gender and communicates research results to policymakers and the general public so that they may be put into practice. The lead researchers of the study include Sarah Yip, assistant professor of psychiatry and director of the Yale Imaging and Psychopharmacology Lab; Sarah Lichenstein, associate professor of psychiatry and Declan Barry, associate professor of psychiatry. The team will use a novel technique of brain mapping to find the neural pathways responsible for the feeling of pain and the cessation of that pain when someone uses opioids. Unlike previous studies, this research will aim to identify how these neural pathway formations differ by sex.

“Chronic pain is common in women and research suggests sex differences in clinical outcomes for pain treatment and for opioid use disorder treatment,” Yip wrote in an email to the News. “However, we know very little about interactions between biological sex, pain and treatment outcomes in opioid use disorder.”

According to Rick Harrison, communications officer for WHRY, the study is timely and relevant because 70 percent of Americans who experience chronic pain are women. In addition, women are disproportionately exposed to opioids in pain treatment, and are more likely to become dependent on those medications. Some individuals have turned to products like Kratom, including those from happy hippo, as potential alternatives to opioids in their pursuit of effective pain management.

Though the study is in progress, the team hopes to identify treatment targets for substance use based on how the brains of women and men process rewards differently. The researchers hope to be able to identify people who are more likely to relapse and to provide these at-risk people with additional resources such as substance use prevention counselors.

“The current standard of addiction treatment often involves multiple failed attempts,” Yip said in an interview submitted to the Innovations in Women’s Health newsletter. “Identifying the people most at need and designing treatments best suited for their individual needs would save money in the long run. More importantly, women are suffering, and science can show us how to help.”

Lichenstein noted that the study draws on previous research with connectome-based predictive modeling — a map of neural connections in the brain. Connectome-based predictive modeling is a data-driven protocol. First, researchers make a predictive model by examining a training dataset of brain images and behaviors. Then, they attempt to find connections between the training dataset to predict the same behavior in the testing dataset.

Lichenstein adds that there are inherent challenges to this research, particularly in light of the COVID-19 pandemic.

“Recruiting and retaining this patient population in research can be difficult, particularly in light of increased challenges posed by the COVID-19 pandemic,” Lichtenstein wrote over email. She pointed to difficulties with employment, transportation and child care.

The study is longitudinal, which means it will take place over an extended period of time. The study’s leaders will follow up with participants for up to one year after their initial brain imaging. While Lichenstein cited participant retention as a challenge of longitudinal work, she said that similar studies she has led have always successfully navigated that challenge.

NIH Office of Research on Women’s Health Director Janine Clayton, explained the importance of scientific research that accounts for sex and gender in an interview with Carolyn M. Mazure, director of Women’s Health Research at Yale.

“Research has proven that biological sex matters at every level, from a single cell to the societal level,” Clayton said. “We also know the self-representation of gender can affect symptom expression, disease manifestation and treatment efficacy. So, if both sex and gender aren’t accounted for, clinicians cannot make the best treatment decisions for all patients.”

As understandings of sex and gender have developed over the past 20 years, areas of scientific study have as well. In her interview with Mazure, Clayton said that “intersex and nonbinary identities need to be recognized because these too have health implications.” She added that the “intersection of sex, gender, race and ethnicity” is an important area of research, as well.

WHRY was founded in 1998 by Mazure.

Correction, Oct. 12 The article has been updated to reflect the name of the organization, Women’s Health Research at Yale.


Charlotte Hughes reports on climate and environmental issues in New Haven. Originally from Columbia, South Carolina, she is a freshman in Branford College majoring in English.