Why personalized pain meds are the way forward

Why personalized pain meds are the way forward

Pain conditions are leading contributors to disability worldwide. Despite this, treatments vary in efficacy between individuals, and some carry a high potential for misuse. Personalized pain medicine is an emerging field that aims to produce safe and effective treatments tailored to individual needs.

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Why is it so important to tailor pain medication to individual needs? Image credit: Courtney Rust/Stocksy.

Around 1.71 billion people live with a pain- or musculoskeletal-related condition globally. These include lower back pain, osteoarthritis, and fibromyalgia. Such conditions are linked to worse mental health and well-being measures, increased work absenteeism, and productivity losses.

Treatment options for pain depend on severity. Milder forms of pain may be treated with over-the-counter drugs such as acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen.

If these drugs fail to provide relief, doctors may prescribe muscle relaxants such as diazepam, NSAIDs such as celecoxib, or steroid treatments like dexamethasone. Aside from these, doctors may also offer opioids, including codeine, fentanyl, and oxycodone, for short-term use.

While each of these drugs is widely used for pain relief, their varied effects and safety profiles have inspired patients and researchers alike to search for more personalized treatment options.

“Our currently available pain management therapeutics are essentially one-size-fits-all. For most pain, we treat it with NSAIDs or opioids,” Dr. Cynthia Renn, professor of pain and translational symptom science at the University of Maryland, told Medical News Today. “There haven’t been any really transformative analgesic discoveries since the identification of the opioids.”

“The NSAIDs and opioids work with more or less efficacy to treat pain from various origins. We know that the one-size-fits-all approach doesn’t work for everyone, given that two people with seemingly the same injury suffer pain differently; some will recover quickly with minimal pain while others will go on to develop chronic pain,” she pointed out.

When asked why some analgesics may work in some and not others, Dr. Kevin Boehnke, a research investigator in the Department of Anesthesiology and the Chronic Pain and Fatigue Research Center at the University of Michigan, explained that there are two key factors.

The first, he noted, is “genetics and metabolism.” He explained:

“People metabolize medicines at different rates. The same dose of the same medication might last longer and have more potent effects in person A, a slow metabolizer, versus person B, a fast metabolizer. These metabolic differences could be due to genetic differences, where some people may have genetic predispositions towards faster or slower metabolism of certain drugs.”

After this, he noted that different types of pain require different treatments due to differing underlying mechanisms. Pain, he said, comes in three “flavors:”

  • nociceptive pain — caused by tissue damage or inflammation such as a burn or broken bone
  • neuropathic pain from nerve damage, impingement, or inflammation such as sciatica or carpal tunnel syndrome
  • nociplastic pain, which cannot be seen through imaging, but researchers think it may be caused by central nervous system dysfunction. It is characterized by widespread pain throughout the body, and includes conditions like fibromyalgia.

“Overall, these flavors of pain may occur in isolation or co-occur, and different types of pain respond differently to treatments. For example, NSAIDs are often useful for nociceptive pain but don’t help much for nociplastic pain,” Dr. Boehnke added.

Dr. Renn explained that “[t]he goal of personalized pain medicines is to discover compounds that work specifically for individual patients or small groups of patients that share a similar genetic profile that will respond to the specific compound(s).”

Key to this, she noted, is identifying biomarkers that determine the best pain management regimens for given patients, and discovering new analgesics and therapeutic strategies based on a person’s genetic profile.

To understand more about such work, MNT spoke with Dr. Jelena M. Janjic, associate professor at the School of Pharmacy at Duquesne University, founder and codirector of the Chronic Pain Research Consortium.

For several years, Dr. Janjic and her team have been working at the crossroads between identifying pain biomarkers and developing therapeutic strategies to personalize treatments for pain.

In particular, they have focused on chronic pain, often characterized by an elevated immune response in certain areas of the body that increases inflammation and, over time, damages nerves, resulting in pain.

The condition is often treated with oral drugs such as the NSAID celecoxib. The oral delivery method, however, means that the drug’s effects are untargeted — it goes on to affect all tissues, even areas where no pain is present.

Such a blanket treatment also requires larger doses than if it were more targeted, ultimately putting patients at risk of negative side effects and toxicity.

To reduce these off-target effects, Dr. Janjic and her team designed a nanomedicine delivery system that essentially “rides” immune cells called macrophages to areas of pain, where they then release anti-inflammatory drugs.

In a recent study, they tested their nanoparticle delivery system with celecoxib on a rat sciatic nerve injury model. They found that rats treated with a single intravenous dose of their celecoxib nanotherapeutic required 2,000 times less of the drug to alleviate pain for 6 days than rats treated orally.

Dr. Janjic and her team noted that this likely happened as the drug was carried only to necessary sites, and interacted with the macrophages themselves, which in turn set off a cascade of effects that ultimately reduced inflammatory signaling.

In another study, her team found that a single dose of the nanomedicine produced 32 days of pain relief in male mice with nerve injury, and 11 days of pain relief in females with the same condition, as compared to the drug-free control group.

By tracking the nanomedicine’s delivery, the researchers observed that sex differences resulted from different macrophage levels between males and females in response to pain.

Dr. Janjic told MNT that her nanomedicine delivery system solves two key problems at once: On the one hand, it can treat chronic pain, and on the other, it can track pharmacological effects in vivo.

Such a dual effect, she noted, could lead to more targeted treatment options and aid research investigating which medicines work best for different individuals as they age and their underlying physiologies change.

While research on how to personalize pain medicines from a pharmaceutical standpoint is ongoing, Dr. Zvi G. Loewy, professor in the Department of Pharmaceutical and Biomedical Sciences at Touro College of Pharmacy, told MNT that personalized pharmacological treatments are already a reality:

“Personalized medications entail delivery of a medication to an individual patient based upon the patient’s genotype and corresponding phenotype. Determination of genotype and phenotype is facilitated by pharmacogenomic testing. […] [Two medical laboratories companies in the U.S.] offer pharmacogenomic testing designed for pain management therapies.”

Dr. Boehnke, however, noted that even as research advances, there will likely be no “silver bullet” medication for pain conditions.

“Frankly, there are risks and costs associated with taking any medication or using any treatment, and no single treatment is typically sufficient to manage chronic pain. This will very likely remain true even as new medications are developed,” he said.

Dr. Boehnke thus recommended a mixed approach that employs “both medications and nonpharmacological therapies to help manage pain and enhance function, with a goal of minimizing side effects and overmedication.”

“Medications are best used to help with pressing symptoms, and to help provide the stability needed to build nonmedication practices that help with pain management,” he added.

He noted that practices not based on medication may include exercise, eating well, sleep hygiene, and managing emotions and mood through breathing exercises, meditation, or prayer.

“If we conceptualize personalized pain medicine only as applying to medications, we are missing a huge swath of evidence-based approaches that are quite low-risk and should be available to patients,” he explained.

Lastly, MNT also spoke with Dr. Richard B. Hovey, associate professor at the Faculty of Dental Medicine and Oral Health Sciences at McGill University. He commented that:

“My decades as a qualitative chronic pain researcher have taught me that even when people share a common diagnosis, we all experience pain differently. Personalized pain medications have the possibility to address this unique situation by going beyond the medical treatment of pain to include the treatment of the whole person.”

“As a person who lives with chronic pain the multiple medical appointments add to the distress, and we move from one expert to another while fatigued by the pain and the side effects of the prescribed medications,” he noted.

“This tension between what is helping me medically is negatively influencing other valued aspects of my life. Perhaps, personalized pain medications would help to humanize the experiences of a life changed, perhaps forever,” he concluded.

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