New drugs target 'zombie cells' to relieve back pain

Lower back pain is one of the most widespread and debilitating conditions in the world. It affects millions of people, often reducing quality of life, limiting mobility, and draining healthcare systems. Despite its enormous impact, most available treatments only dull the pain; they do not fix it.

People with this chronic pain rely on painkillers, physical therapy, or invasive surgery. While these options may help some patients cope, they don’t fix the underlying problem. That may soon change, thanks to a team of researchers at McGill University.

In a recent preclinical study, the experts explored a radically different approach. Instead of masking the pain, they aimed to treat its root cause – damaged cells in the spine, known as “zombie cells.”

These senescent cells don’t die when they should. They accumulate in spinal discs, spreading inflammation and tissue damage. The researchers tested two drugs that clear these cells from the body. The results, they say, could transform how chronic back pain is treated.

“Our findings are exciting because it suggests we might be able to treat back pain in a completely new way, by removing the cells driving the problem, not just masking the pain,” said Professor Lisbet Haglund, senior author and co-director of the Orthopaedic Research Laboratory at the Montreal General Hospital.

This study is a step toward developing therapies that tackle the biological drivers of pain, not just its symptoms.

Zombie cells in the spine fuel inflammation

As people age, or experience stress and injury, senescent cells begin to gather in tissues throughout the body.

In the spinal column, they settle into the intervertebral discs – the cushion-like pads that lie between vertebrae, absorb shock, and help with movement. These cells release a cocktail of damaging molecules known as the senescence-associated secretory phenotype (SASP).

This mix includes inflammatory cytokines, enzymes, and signaling molecules that degrade surrounding tissue. They create a toxic environment that promotes further cell damage, inflammation, and disc degeneration.

As the discs deteriorate, spinal pain worsens and becomes more resistant to traditional treatments. The team at McGill focused on these zombie cells as the key culprits behind chronic lower back pain.

The researchers used a mouse model known as sparc^−/− that lack a gene that is associated with healthy spinal disc maintenance.

As a result, they develop early-onset disc degeneration and back pain similar to human patients. This model allowed the scientists to test whether eliminating zombie cells could actually reduce pain and restore tissue health.

Drugs relieved back pain in mice

The study investigated the effects of two drugs for back pain: o-Vanillin, a natural compound derived from turmeric, and RG-7112, a synthetic drug that was originally developed for cancer treatment.

The drug o-Vanillin is known for its anti-inflammatory properties, while RG-7112 works by interfering with a protein complex that helps zombie cells avoid death.

Both drugs were administered orally over eight weeks. Remarkably, the treatment reduced inflammation in the mice, removed senescent cells, and even reversed damage to the discs.

Although each drug worked on its own, their combination yielded the strongest results. The researchers observed improvements in grip strength, decreased cold and mechanical sensitivity, and fewer signs of discomfort in mice.

“We were surprised that an oral treatment could reach the spinal discs, which are hard to access and present a major hurdle in treating back pain,” said Haglund. “The big question now is whether these drugs can have the same effect in humans.”

Their success in reaching the discs, which are shielded from many medications, adds another layer of excitement to the findings.

How the drugs work for back pain

To understand the mechanism behind the improvements, the team studied the effects of the drugs on a molecular level.

Both drugs reduced levels of SASP factors like IL-6, TNF-α, and VEGF-α, molecules known to worsen inflammation and accelerate tissue decay. In spinal discs, levels of the senescence marker p16Ink4a decreased significantly, showing that the treatment was clearing out harmful cells.

This cellular cleanup translated to real improvements. Treated mice showed healthier discs, better separation between disc layers, and restored disc volume. These changes indicate the potential for actual tissue repair, not just temporary pain relief.

When the two drugs were given together at full strength, the benefits were magnified. Reducing either drug by half weakened the response, and cutting both reduced the effect significantly.

In untreated mice, signs of degeneration continued. Their spinal discs shrank, pain increased, and inflammatory markers remained high. But in treated animals, disc structure and bone density improved.

Treatment calmed nerve activity

Pain isn’t just caused by physical damage. It is also shaped by how the nervous system processes signals from the spine.

The researchers examined the spinal cords of treated mice and found that senolytic therapy also had effects there. They recorded lower activity of key proteins like CGRP and GFAP – both of which are involved in amplifying pain in the nervous system.

This suggests that the drugs may relieve back pain by calming down the pain-processing machinery in the spinal cord. Both o-Vanillin and RG-7112 reduced these markers, but the combination again delivered the greatest effect. Reducing inflammation in the spinal cord may help stop the cycle of chronic pain.

The study also showed reduced activation of microglia, which are immune cells in the brain and spinal cord that can worsen pain, if overstimulated. Taken together, the findings suggest that the therapy not only heals the spine but also reduces the brain’s sensitivity to pain signals.

Innovative drugs for back pain

The drug o-Vanillin wasn’t even supposed to be in the original study. It was added as a side compound during early testing. Yet its impact turned out to be crucial.

This turmeric-based molecule is not only effective at reducing inflammation but may also have unique properties that let it penetrate tough tissues like spinal discs and even the brain.

Pharmacokinetic analysis revealed that o-Vanillin is quickly distributed throughout the body and may accumulate in fat tissue, allowing it to act over time. Its high clearance rate suggests rapid dispersal, yet its lipophilic structure helps it reach hard-to-access areas. These traits make it a promising candidate for long-term use in treating chronic conditions.

The researchers plan to improve the structure of o-Vanillin so that it lasts longer in the body. This could increase its effectiveness and allow for the use of lower doses in future trials.

Treating back pain in humans

Perhaps the most encouraging takeaway is that the drug doses used in mice translate to feasible doses in humans.

Using standard dose conversion, the human equivalent would be about 8 mg/kg for o-Vanillin and 0.4 mg/kg for RG-7112. These amounts are manageable and below the toxic levels seen in cancer patients treated with high doses of RG-7112.

No adverse effects were noted during the eight-week mouse trial. The mice maintained normal activity, body weight, and behavior.

This suggests the therapy is safe, at least in the short term. Before human trials can begin, though, more studies are needed. The researchers plan to test in larger animal models and explore advanced drug delivery methods.

Age-related diseases beyond back pain

The implications go beyond the treatment of back pain. Senescent cells contribute to many age-related diseases – arthritis, osteoporosis, and even neurodegeneration. By removing these harmful cells, senolytic drugs could become a universal tool to manage aging-related health issues.

“The big question now is whether these drugs can have the same effect in humans,” Haglund said. If they do, this could signal a shift in medicine – from treating symptoms to correcting root causes.

The study, published in Science Advances, was led by Matthew Mannarino, Hosni Cherif, and Lisbet Haglund. The research was supported by the Canadian Institutes of Health Research and other partners.

This work shines a light on a hopeful future where aging tissues can be renewed and pain reversed – not just endured.

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