Men and Women Experience Pain Differently. Learning Why Could Lead to Better Drugs.
It's been more than a decade since Jeannette Rotondi has been pain-free. A licensed social worker, she lives with five chronic pain diagnoses, including migraines. After years of exploring treatment options, doctors found one that lessened the pain enough to allow her to "at least get up."
"With all that we know now about genetics and the immune system, I think the future of pain medicine is more precision-based."
Before she says, "It was completely debilitating. I was spending time in dark rooms. I got laid off from my job." Doctors advised against pregnancy; she and her husband put off starting a family for almost a decade.
"Chronic pain is very unpredictable," she says. "You cannot schedule when you'll be in debilitative pain or cannot function. You don't know when you'll be hit with a flare. It's constantly in your mind. You have to plan for every possibly scenario. You need to carry water, medications. But you can't plan for everything." Even odors can serve as a trigger.
According to the CDC, one fifth of American adults live with chronic pain, and women are affected more than men. Do men and women simply vary in how much pain they can handle? Or is there some deeper biological explanation? The short answer is it's a little of both. But understanding the biological differences can enable researchers to develop more effective treatments.
While studies in animals are straightforward (they either respond to pain or they don't), humans are more complex. Social and psychological factors can affect the outcome. For example, one Florida study found that gender role expectations influenced pain sensitivity.
"If you are a young male and you believe very strongly that men are tougher than women, you will have a much higher threshold and will be less sensitive to pain," says Robert Sorge, an associate professor at the University of Alabama at Birmingham whose lab researches the immune system's involvement in pain and addiction.
He also notes, "We looked at transgender women and their pain sensitivity in comparison to cis men and women. They show very similar pain sensitivity to cis women, so that may reduce the impact of genetic sex in terms of what underlies that sensitivity."
But the difference goes deeper than gender expectations. There are biological differences as well. In 2015, Sorge and his team discovered that pain stimuli activated different immune cells in male and female rodents and that the presence of testosterone seemed to be a factor in the response.
More recently, Ted Price, professor of neuroscience at University of Texas, Dallas, examined pain at a genetic level, specifically looking at the patterns of RNA, which are single-stranded molecules that act as a messenger for DNA. Price noted that there were differences in these patterns that coincided with whether an individual experienced pain.
Price explains, "Every cell in your body has DNA, but the RNA that is in the cells is different for every cell type. The RNA in any particular cell type, like a neuron, can change as a result of some environmental influence like an injury. We found a number of genes that are potentially causative factors for neuropathic pain. Those, interestingly, seemed to be different between men and women."
Differences in treatment also affect pain response. Sorge says, "Women are experiencing more pain dismissal and more hostility when they report chronic pain. Women are more likely to have their pain associated with psychological issues." He adds that this dismissal may require women to exaggerate symptoms in order to be believed.
This can impact pain management. "Women are more likely to be prescribed and to use opioids," says Dr. Roger B. Fillingim, Director of Pain Research and Intervention Center of Excellence at the University of Florida. Yet, when self-administering pain meds, "women used significantly less opioids after surgery than did men." He also points out that "men are at greater risk for dose escalation and for opioid-related death than are women. So even though more women are using opioids, men are more likely to die from opioid-related causes."
Price acknowledges that other drugs treat pain, but "unfortunately, for chronic pain, none of these drugs work very well. We haven't yet made classes of drugs that really target the underlying mechanism that causes people to have chronic pain."
New drugs are now being developed that "might be particularly efficacious in women's chronic pain."
Sorge points out that there are many variables in pain conditions, so drugs that work for one may be ineffective for another. "With all that we know now about genetics and the immune system, I think the future of pain medicine is more precision-based, where based on your genetics, your immune status, your history, we may eventually get to the point where we can say [certain] drugs have a much bigger chance of working for you."
It will take some time for these new discoveries to translate into effective treatments, but Price says, "I'm excited about the opportunities. DNA and RNA sequencing totally changes our ability to make these therapeutics. I'm very hopeful." New drugs are now being developed that "might be particularly efficacious in women's chronic pain," he says, because they target specific receptors that seem to be involved when only women experience pain.
Earlier this year, three such drugs were approved to treat migraines; Rotondi recently began taking one. For Rotondi, improved treatments would allow her to "show up for life. For me," she says, "it would mean freedom."
A sleek, four-foot tall white robot glides across a cafe storefront in Tokyo’s Nihonbashi district, holding a two-tiered serving tray full of tea sandwiches and pastries. The cafe’s patrons smile and say thanks as they take the tray—but it’s not the robot they’re thanking. Instead, the patrons are talking to the person controlling the robot—a restaurant employee who operates the avatar from the comfort of their home.
It’s a typical scene at DAWN, short for Diverse Avatar Working Network—a cafe that launched in Tokyo six years ago as an experimental pop-up and quickly became an overnight success. Today, the cafe is a permanent fixture in Nihonbashi, staffing roughly 60 remote workers who control the robots remotely and communicate to customers via a built-in microphone.
More than just a creative idea, however, DAWN is being hailed as a life-changing opportunity. The workers who control the robots remotely (known as “pilots”) all have disabilities that limit their ability to move around freely and travel outside their homes. Worldwide, an estimated 16 percent of the global population lives with a significant disability—and according to the World Health Organization, these disabilities give rise to other problems, such as exclusion from education, unemployment, and poverty.
These are all problems that Kentaro Yoshifuji, founder and CEO of Ory Laboratory, which supplies the robot servers at DAWN, is looking to correct. Yoshifuji, who was bedridden for several years in high school due to an undisclosed health problem, launched the company to help enable people who are house-bound or bedridden to more fully participate in society, as well as end the loneliness, isolation, and feelings of worthlessness that can sometimes go hand-in-hand with being disabled.
“It’s heartbreaking to think that [people with disabilities] feel they are a burden to society, or that they fear their families suffer by caring for them,” said Yoshifuji in an interview in 2020. “We are dedicating ourselves to providing workable, technology-based solutions. That is our purpose.”
Shota Kuwahara, a DAWN employee with muscular dystrophy. Ory Labs, Inc.
Wanting to connect with others and feel useful is a common sentiment that’s shared by the workers at DAWN. Marianne, a mother of two who lives near Mt. Fuji, Japan, is functionally disabled due to chronic pain and fatigue. Working at DAWN has allowed Marianne to provide for her family as well as help alleviate her loneliness and grief.Shota, Kuwahara, a DAWN employee with muscular dystrophy, agrees. "There are many difficulties in my daily life, but I believe my life has a purpose and is not being wasted," he says. "Being useful, able to help other people, even feeling needed by others, is so motivational."
When a patient is diagnosed with early-stage breast cancer, having surgery to remove the tumor is considered the standard of care. But what happens when a patient can’t have surgery?
Whether it’s due to high blood pressure, advanced age, heart issues, or other reasons, some breast cancer patients don’t qualify for a lumpectomy—one of the most common treatment options for early-stage breast cancer. A lumpectomy surgically removes the tumor while keeping the patient’s breast intact, while a mastectomy removes the entire breast and nearby lymph nodes.
Fortunately, a new technique called cryoablation is now available for breast cancer patients who either aren’t candidates for surgery or don’t feel comfortable undergoing a surgical procedure. With cryoablation, doctors use an ultrasound or CT scan to locate any tumors inside the patient’s breast. They then insert small, needle-like probes into the patient's breast which create an “ice ball” that surrounds the tumor and kills the cancer cells.
Cryoablation has been used for decades to treat cancers of the kidneys and liver—but only in the past few years have doctors been able to use the procedure to treat breast cancer patients. And while clinical trials have shown that cryoablation works for tumors smaller than 1.5 centimeters, a recent clinical trial at Memorial Sloan Kettering Cancer Center in New York has shown that it can work for larger tumors, too.
In this study, doctors performed cryoablation on patients whose tumors were, on average, 2.5 centimeters. The cryoablation procedure lasted for about 30 minutes, and patients were able to go home on the same day following treatment. Doctors then followed up with the patients after 16 months. In the follow-up, doctors found the recurrence rate for tumors after using cryoablation was only 10 percent.
For patients who don’t qualify for surgery, radiation and hormonal therapy is typically used to treat tumors. However, said Yolanda Brice, M.D., an interventional radiologist at Memorial Sloan Kettering Cancer Center, “when treated with only radiation and hormonal therapy, the tumors will eventually return.” Cryotherapy, Brice said, could be a more effective way to treat cancer for patients who can’t have surgery.
“The fact that we only saw a 10 percent recurrence rate in our study is incredibly promising,” she said.