Finding the Link Between Pain Sensitivity and Opioid Addiction

As a social worker, Andre B. Toussaint’s mother spent her career helping people who were battling mental health conditions on multiple fronts, such as schizophrenia combined with substance abuse disorder. Growing up hearing about his mother’s work, Toussaint became fascinated by the complexities of the brain and human behavior. He wondered what he could do to help those who were facing behavioral or mental-health challenges.

It’s perhaps no surprise that today Toussaint is a behavioral neuroscientist working to elucidate the connection between susceptibility to pain and the risk of becoming addicted to opioids — a link that has long been observed but never fully explored.

A first-year Junior Fellow with the Simons Society of Fellows and a first-year postdoctoral fellow at Columbia University’s Zuckerman Institute, Toussaint counts his eldest brother — a Ph.D.-level chemical engineer — as another major influence in his career path, and a mentor to this day. By introducing Toussaint to chemistry and other related fields, his brother gave Toussaint the foundation he needed to be skeptical of claims that aren’t backed by solid data. Additional mentors, such as Toussaint’s doctoral advisor at Temple University, Mathieu Wimmer, and Ishmail Abdus-Saboor, his current postdoctoral advisor at Columbia, have also played a pivotal role in his research focus.

Toussaint and I recently discussed his work and its implications, as well as his desire to be an inspiration to others. Our conversation has been edited for clarity.

What is the thrust of your research?

Many members of our lab are investigating the science of pain from different angles — from developing new tools to assess pain, to mapping the underlying mechanisms and brain pathways involved. I focus on the ways we feel pain, and how this links up with proclivity to addiction — an intriguing connection that has begun to warrant much scientific interest. Working with mice, I use a combination of high-speed video cameras, machine learning and mathematical modeling to address these research questions.

The classic method of measuring pain in rodents involves a yes-no index, which is based on whether the rodent retracts its paw or not in response to stimuli. However, since pain is very subjective and can vary between individuals — what’s painful to me may not be painful to you — we developed a new objective pain scale that does not rely on this classic method.

My research, both during graduate school at Temple and now at Columbia, involves working with rodents to assess vulnerability to maladaptive drug use across generations. Specifically, I examine the intergenerational consequences of a father’s chronic exposure to opioids. This research has given me expertise in understanding opioid addiction within families. The current opioid epidemic can ultimately be largely attributable to poor pain management, so this work was a beautiful marriage between the lab’s focus on pain and my expertise in assessing vulnerability to drug abuse. The very long-term goal of this work is to develop nonaddictive treatments for people to manage their pain, and that begins with basic science research using animal models like rodents.

What are the benefits and challenges of working with rodents to study pain and addiction?

Humans are far more complex than rodents, of course. There’s so much that goes into how humans experience and express pain, so it’s difficult to mimic the human experience exactly, especially as our work with rodents exists in controlled experimental environments.

That being said, rodents make for excellent models in our work. They are genetically similar to humans and respond to drugs in similar ways; the same brain regions are activated in both rodents and in humans. So, while imperfect, they really are the best model we have to mimic the human condition.

Can you tell us more about your doctoral work at Temple University?

At Temple, one of my projects focused on the multigenerational effects of paternal morphine exposure. We exposed male rats to morphine for 60 days, which covered the entire cycle it takes for their sperm cells to mature. We then bred these male rats with a female rat who had not been exposed to any drugs. We also bred drug-free male rats as a control.

We found that the male offspring derived from morphine-exposed fathers had significantly more mu-opioid receptors in the ventral tegmental area of the brain — an important region involved in reward processing and motivation. These males self-administered more morphine and worked harder to get it. Although this effect only occurred in the male offspring, we did observe in another study that female offspring exhibited memory deficits, demonstrating that a father’s drug exposure — at least in rodents — could produce long-term maladaptive effects that vary by sex. This work is currently under review for publication.

In a second set of experiments, we found that male offspring of the morphine-exposed fathers were more sensitive to morphine’s pain-relieving effects, as compared to controls. This finding may help illuminate why a family history of drug use may play a role in future generations’ susceptibility to addiction. We published this work in Science Advances in 2022. Two of my mentors, Drs. Wimmer and Abdus-Saboor, served as the senior authors, with myself as first author.

What are you working on now?

We have a couple of ongoing projects at the Zuckerman Institute. One is with a unique mouse model that experiences pain even with nonpainful stimuli (a condition known as mechanical allodynia), while also reacting excessively to legitimate pain (this is called mechanical hyperalgesia). Given that this particular mouse model has such unique characteristics related to pain, will it be especially likely to find opioids — or even pain relievers more generally — rewarding? That’s what I hope to find out.

I am also involved with larger lab-wide efforts, which are not just focused on the neuroscience of pain but also on pleasure. In January 2023 some of my colleagues in the lab published a paper in Cell that identified the neurons in the skin of female mice that mediate the feeling of pleasurable touch. Alongside collaborators at the University of Washington, Seattle, I am now studying whether these same touch neurons are implicated in sexual pleasure, specifically genital stimulation.

Finally, what are your thoughts about the Simons Junior Fellowship?

I just want to acknowledge upfront that the support that the Junior Fellowship provides is amazing, which I truly appreciate. In addition, I feel like I am part of an amazing support system of scientists. The dinners are always stimulating, and it really is true that you are sitting shoulder-to-shoulder with leaders in their fields.

To conclude, let me say this: I chose this career because I love learning and love science. But I’m also doing this for the greater good and for people who may be thinking about embarking on a career in science or medicine. There aren’t many Junior Fellows who, like me, are Caribbean-American — I was born on the island of Trinidad and Tobago — and so it is my sincere desire that I can serve as an inspiration to others with a similar background.