A New Test Aims to Objectively Measure Pain. It Could Help Legitimate Sufferers Access the Meds They Need.
"That throbbing you feel for the first minute after a door slams on your finger."
This is how Central Florida resident Bridgett Willkie describes the attacks of pain caused by her sickle cell anemia – a genetic blood disorder in which a patient's red blood cells become shaped like sickles and get stuck in blood vessels, thereby obstructing the flow of blood and oxygen.
"I found myself being labeled as an addict and I never was."
Willkie's lifelong battle with the condition has led to avascular necrosis in both of her shoulders, hips, knees and ankles. This means that her bone tissue is dying due to insufficient blood supply (sickle cell anemia is among the medical conditions that can decrease blood flow to one's bones).
"That adds to the pain significantly," she says. "Every time my heart beats, it hurts. And the pain moves. It follows the path of circulation. I liken it to a traffic jam in my veins."
For more than a decade, she received prescriptions for Oxycontin. Then, four years ago, her hematologist – who had been her doctor for 18 years – suffered a fatal heart attack. She says her longtime doctor's replacement lacked experience treating sickle cell patients and was uncomfortable writing her a prescription for opioids. What's more, this new doctor wanted to place her in a drug rehab facility.
"Because I refused to go, he stopped writing my scripts," she says. The ensuing three months were spent at home, detoxing. She describes the pain as unbearable. "Sometimes I just wanted to die."
One of the effects of the opioid epidemic is that many legitimate pain patients have seen their opioids significantly reduced or downright discontinued because of their doctors' fears of over-prescribing addictive medications.
"I found myself being labeled as an addict and I never was...Being treated like a drug-seeking patient is degrading and humiliating," says Willkie, who adds that when she is at the hospital, "it's exhausting arguing with the doctors...You dread them making their rounds because every day they come in talking about weaning you off your meds."
Situations such as these are fraught with tension between patients and doctors, who must remain wary about the risk of over-prescribing powerful and addictive medications. Adding to the complexity is that it can be very difficult to reliably assess a patient's level of physical pain.
However, this difficulty may soon decline, as Indiana University School of Medicine researchers, led by Dr. Alexander B. Niculescu, have reportedly devised a way to objectively assess physical pain by analyzing biomarkers in a patient's blood sample. The results of a study involving more than 300 participants were published earlier this year in the journal Molecular Psychiatry.
Niculescu – who is both a professor of psychiatry and medical neuroscience at the IU School of Medicine – explains that, when someone is in severe physical pain, a blood sample will show biomarkers related to intracellular adhesion and cell-signaling mechanisms. He adds that some of these biomarkers "have prior convergent evidence from animal or human studies for involvement in pain."
Aside from reliably measuring pain severity, Niculescu says blood biomarkers can measure the degree of one's response to treatment and also assess the risk of future recurrences of pain. He believes this new method's greatest benefit, however, might be the ability to identify a number of non-opioid medications that a particular patient is likely to respond to, based on his or her biomarker profile.
Clearly, such a method could be a gamechanger for pain patients and the professionals who treat them. As of yet, health workers have been forced to make crucial decisions based on their clinical impressions of patients; such impressions are invariably subjective. A method that enables people to prove the extent of their pain could remove the stigma that many legitimate pain patients face when seeking to obtain their needed medicine. It would also improve their chances of receiving sufficient treatment.
Niculescu says it's "theoretically possible" that there are some conditions which, despite being severe, might not reveal themselves through his testing method. But he also says that, "even if the same molecular markers that are involved in the pain process are not reflected in the blood, there are other indirect markers that should reflect the distress."
Niculescu expects his testing method will be available to the medical community at large within one to three years.
Willkie says she would welcome a reliable pain assessment method. Well-aware that she is not alone in her plight, she has more than 500 Facebook friends with sickle cell disease, and she says that "all of their opioid meds have been restricted or cut" as a result of the opioid crisis. Some now feel compelled to find their opioids "on the streets." She says she personally has never obtained opioids this way. Instead, she relies on marijuana to mitigate her pain.
Niculescu expects his testing method will be available to the medical community at large within one to three years: "It takes a while for things to translate from a lab setting to a commercial testing arena."
In the meantime, for Willkie and other patients, "we have to convince doctors and nurses that we're in pain."
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five:
- Research on a "smart" bandage for wounds
- A breakthrough in fighting inflammation
- The pros and cons of a new drug for Alzheimer's
- Benefits of the Mediterranean diet - with a twist
- How to recycle a plastic that was un-recyclable
Sexually transmitted infections (STIs) are surging across the U.S. to 2.5 million cases in 2021 according to preliminary data from the CDC. A new prevention and treatment strategy now in clinical trials may provide a way to get a handle on them.
It's easy to overlook the soaring rates of gonorrhea, chlamydia, and syphilis because most of those infections have few or no symptoms and can be identified only through testing. But left untreated, they can lead to serious damage to nerves and tissue, resulting in infertility, blindness, and dementia. Infants developing in utero are particularly vulnerable.
Covid-19 played havoc with regular medical treatment and preventive care for many health problems, including STIs. After formal lockdowns ended, many people gradually became more socially engaged, with increases in sexual activity, and may have prioritized these activities over getting back in touch with their doctors.
A second blow to controlling STIs is that family planning clinics are closing left and right because of the Dobbs decision and legislation in many states that curtailed access to an abortion. Discussion has focused on abortion, but those same clinics also play a vital role in the diagnosis and treatment of STIs.
Routine public health is the neglected stepchild of medicine. It is called upon in times of crisis but as that crisis resolves, funding dries up. Labs have atrophied and personnel have been redirected to Covid, “so access to routine screening for STIs has been decimated,” says Jennifer Mahn, director of sexual and clinical health with the National Coalition of STD Directors.
A preview of what we likely are facing comes from Iowa. In 2017, the state legislature restricted funding to family health clinics in four counties, which closed their doors. A year later the statewide rate of gonorrhea skyrocketed from 83 to 153.7 cases per 100,000 people. “Iowa counties with clinic closures had a significantly larger increase,” according to a study published in JAMA. That scenario likely is playing out in countless other regions where access to sexual health care is shrinking; it will be many months before we have the data to know for sure.
A decades-old antibiotic finds a new purpose
Using drugs to protect against HIV, either as post exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP), has proven to be quite successful. Researchers wondered if the same approach might be applied to other STIs. They focused on doxycycline, or doxy for short. One of the most commonly prescribed antibiotics in the U.S., it’s a member of the tetracycline family that has been on the market since 1967. It is so safe that it’s used to treat acne.
Two small studies using doxy suggested that it could work to prevent STIs. A handful of clinical trials by different researchers and funding sources set out to generate the additional evidence needed to prove their hypothesis and change the standard of care.
Senior researcher Victor Omollo, with the Kenya Medical Research Institute, noted, “These are prevention interventions that women can control on their own without having to seek or get consent from another person,” as is the case with condom use.
The first with results is the DoxyPEP study, conducted at two sexual health clinics in San Francisco and Seattle. It drew from a mix of transgender women and men who have sex with men, who had at least one diagnosed STI over the last year. The researchers divided the participants into two groups: one with people who were already HIV-positive and engaged in care, while the other group consisted of people who were on PrEP to prevent infection with HIV. For the active part of the study, a subset of the participants received doxy, and the rest of the participants did not.
The researchers intentionally chose to do the study in a population at the highest risk of having STIs, who were very health oriented, and “who were getting screened every three months or so as part of their PrEP program or their HIV care program,” says Connie Celum, a senior researcher at the University of Washington on the study.
Each member of the active group was given a supply of doxy and asked to take two pills within 72 hours of having sex where a condom was not used. The study was supposed to run for two years but, in May, it stopped halfway through, when a safety monitoring board looked at the data and recommended that it would be unethical to continue depriving the control group of the drug’s benefits.
Celum presented these preliminary results from the DoxyPEP study in July at the International AIDS Conference in Montreal. “We saw about a 56 percent reduction in gonorrhea, about 80 percent reduction in chlamydia and syphilis, so very significant reductions, and this is on a per quarter basis,” she told a later webinar.
In Kenya, another study is following a group of cisgender women who are taking the same two-pill regimen to prevent HIV, and the data from this research should become available in 2023. Senior researcher Victor Omollo, with the Kenya Medical Research Institute, noted that “these are prevention interventions that women can control on their own without having to seek or get consent from another person,” as is the case with condom use, another effective prevention tool.
Antibiotic resistance is a potentially big concern. About 25 percent of gonorrhea strains circulating in the U.S. are resistant to the tetracycline class of drugs, including doxy; rates are higher elsewhere. But resistance often is a matter of degree and can be overcome with a larger or longer dose of the drug, or perhaps with a switch to another drug or a two-drug combination.
Research has shown that an established bacterial infection is more difficult to treat because it is part of a biofilm, which can leave only a small portion or perhaps none of the cell surface exposed to a drug. But a new infection, even one where the bacteria is resistant to a drug, might still be vulnerable to that drug if it's used before the bacterial biofilm can be established. Preliminary data suggests that may be the case with doxyPEP and drug resistant gonorrhea; some but not all new drug resistant infections might be thwarted if they’re treated early enough.
“There are some tradeoffs” to these interventions, Celum says, and people may disagree on the cost of increased resistance balanced against the benefits of treating the STIs and reducing their spread within the community.
Resistance does not seem to be an issue yet for chlamydia and syphilis even though doxy has been a recommended treatment for decades, but a remaining question is whether broader use of doxy will directly worsen antibiotic resistance in gonorrhea, or promote it in other STIs. And how will it affect the gut microbiome?
In addition, Celum notes that we need to understand whether doxy will generate mutations in other bacteria that might contribute to drug resistance for gonorrhea, chlamydia or syphilis. The studies underway aim to provide data to answer these questions.
“There are some tradeoffs” to these interventions, Celum says, and people may disagree on the cost of increased resistance balanced against the benefits of treating the STIs and reducing their spread within the community. That might affect doctors' willingness to prescribe the drug.
Turning research into action
The CDC makes policy recommendations for prevention services such as taking doxy, requiring some and leaving others optional. Celum says the CDC will be reviewing information from her trial at a meeting in December, but probably will wait until that study is published before making recommendations, likely in 2023. The San Francisco Department of Public Health issued its own guidance on October 20th and anecdotally, some doctors around the country are beginning to issue prescriptions for doxy to select patients.
About half of new STIs occur in young people ages 15 to 24, a group that is least likely to regularly see a doctor. And sexual health remains a great taboo for many people who don't want such information on their health record for prying parents, employers or neighbors to find out.
“People will go out of their way and travel extensive distances just to avoid that,” says Mahn, the National Coalition director. “People identify locations where they feel safe, where they feel welcome, where they don't feel judged,” Mahn explains, such as community and family planning clinics. They understand those issues and have fees that vary depending on a person’s ability to pay.
Given that these clinics already are understaffed and underfunded, they will be hard pressed to expand services covering the labor intensive testing and monitoring of a doxyPEP regimen. Sexual health clinics don't even have a separate line item in the federal budget for health. That is something the National Association of STI Directors is pushing for in D.C.
DoxyPEP isn't a panacea, and it isn't for everyone. “We really want to try to reach that population who is most likely going to have an STI in the next year,” says Celum, “Because that's where you are going to have the biggest impact.”