Scientists have discovered that the body can naturally dull pain through its own localized “benzodiazepine-like” peptides.
A groundbreaking study led by a University of Leeds scientist has unveiled new insights into how the body manages pain, offering a potential path toward treating long-term pain without relying on addictive opioids.
Professor Nikita Gamper, from the School of Biomedical Sciences at Leeds, and his research team discovered that the human body can generate its own form of natural “sleeping pills” that resemble benzodiazepines. These substances can reduce signals from specific nerves, influencing how intensely pain is felt.
The research, which builds upon earlier studies conducted by Professor Gamper and Professor Xiaona Du of Hebei Medical University in Shijiazhuang, China, could mark a turning point in pain management. With new funding secured for the coming year, the team plans to continue exploring how this biological process could lead to safer, more effective treatments for people suffering from chronic pain.
A New Path Beyond Opioids
Professor Gamper said: “We understand quite a bit about how a person ends up feeling pain, but we can’t do much about it. Despite all the amazing discoveries and textbooks written, opioids are still the gold standard.
“Nothing substantially better than opioids has been produced. If you suffer from pain, you will likely end up with either ibuprofen, which is OK for mild pain, but absolutely does nothing for very strong pain or neuropathic pain; or opioids which are very efficacious but dangerous.”
Benzodiazepines (‘benzos’) are a type of depressant medication commonly prescribed to help with sleep problems, anxiety, and seizures. In their research, Professor Nikita Gamper, Professor Xiaona Du, and Dr. Temugin Berta from the University of Cincinnati discovered that certain cells connected to human nerves, located within structures known as spinal ganglia, can release a peptide that operates in a similar way to benzos.
Because this process takes place only within the peripheral nervous system, it does not cause the entire nervous system to “go to sleep.” As a result, these naturally produced peptides could offer pain relief without the dangerous side effects or risk of addiction associated with opioid drugs.
The study’s results show that nerves are capable of “tuning out” pain signals or limiting how much pain the brain perceives, revealing a potential new mechanism for controlling discomfort at its source.
Turning Down Pain at Its Source
Dr. Ganesan Baranidharan, a consultant in pain medicine in Leeds, said the findings could offer some hope to patients trying to manage daily chronic pain.
He said: “Chronic pain is one of the health service’s biggest problems.
“In clinics we try to manage pain with ‘self management’ – learning to live with pain – or we try to help where we can with physiotherapy, injections, or surgeries. However, some patients will have persistent pain needing medicines, and long-term use of nerve painkillers and opioids can cause significant side effects such as feeling like a zombie, memory impairment, etc.
“While some patients do really well on small dose opioids, we need more options to treat chronic pain. The more we can discover, and find appropriate drugs to treat certain conditions, the better for our patients.”
Toward Safer Pain Treatments
Professor Nikita’s findings – published in the Journal of Clinical Investigation (JCI) – open up the possibility of developing new, targeted medicines that could block pain signals without crossing the blood-brain barrier and affecting other brain functions.
For up to a third of the world’s population, pain is a daily burden, and despite being the primary reason for doctor visits across the world, pain is still poorly treated.
Cincinnati’s Dr. Berta, whose research is sponsored by the NIH HEAL initiative, added: “Millions of people suffer from chronic pain and more than half have trouble finding adequate relief. As pain scientists, we have the opportunity to discover new mechanisms that contribute to the progression of chronic pain and share breakthroughs that may hold promise for new treatment strategies.”
Professor Gamper’s decision to focus his work in this area was strongly influenced by seeing a member of his immediate family suffer with neuropathic pain.
He added: “Pain is an interesting phenomenon to study, but ultimately it’s not curiosity that drives you, it’s the ability or at least opportunity to relieve people from pain.”
The teams in Leeds and Shijiazhuang worked together from the research’s inception, with Dr. Berta in Cincinnati coming on board after the scientists discussed their work at a Society for Neuroscience conference in 2018.
Although the scientists had not previously met, they knew each other’s wor,k and by sharing knowledge, they soon realized they had been working on similar experiments and produced identical results. Dr. Berta believes their work “embodies the collaborative spirit of academic research” and shows how significant advancements in understanding and treating pain can be made when scientists work together.
Professor Du said: “I vividly recall the excitement when Nikita informed me that Temo’s lab had obtained similar primary results to ours, solidifying our decision to pursue the study further.
“I hope that our future collaboration will yield even more and better outcomes.”
New Research Funding
A research team led by Professor Gamper in Leeds has now received £3.5 million in funding from the Medical Research Council and the pharmaceutical industry to look further into their findings. A new project was started in January 2025 and will run for five years, looking more closely at potential markers of neuropathic pain and new approaches for pain management, incorporating this new knowledge about spinal ganglia and the ‘benzo’ peptide.
Reference: “Peripheral gating of mechanosensation by glial diazepam binding inhibitor” by Xinmeng Li, Arthur Silveira Prudente, Vincenzo Prato, Xianchuan Guo, Han Hao, Frederick Jones, Sofia Figoli, Pierce Mullen, Yujin Wang, Raquel Tonello, Sang Hoon Lee, Shihab Shah, Benito Maffei, Temugin Berta, Xiaona Du and Nikita Gamper, 18 June 2024, The Journal of Clinical Investigation.
DOI: 10.1172/JCI176227
Funding: Wellcome Trust, Medical Research Council, Biotechnology and Biological Sciences Research Council, Biotechnology and Biological Sciences Research Council, Horizon 2020 Framework Programme, National Natural Science Foundation of China, Science Fund for Creative Research Groups, NIH/National Institute of Neurological Disorders and Stroke
News
Platelet-inspired nanoparticles could improve treatment of inflammatory diseases
Scientists have developed platelet-inspired nanoparticles that deliver anti-inflammatory drugs directly to brain-computer interface implants, doubling their effectiveness. Scientists have found a way to improve the performance of brain-computer interface (BCI) electrodes by delivering anti-inflammatory drugs directly [...]
After 150 years, a new chapter in cancer therapy is finally beginning
For decades, researchers have been looking for ways to destroy cancer cells in a targeted manner without further weakening the body. But for many patients whose immune system is severely impaired by chemotherapy or radiation, [...]
Older chemical libraries show promise for fighting resistant strains of COVID-19 virus
SARS‑CoV‑2, the virus that causes COVID-19, continues to mutate, with some newer strains becoming less responsive to current antiviral treatments like Paxlovid. Now, University of California San Diego scientists and an international team of [...]
Lower doses of immunotherapy for skin cancer give better results, study suggests
According to a new study, lower doses of approved immunotherapy for malignant melanoma can give better results against tumors, while reducing side effects. This is reported by researchers at Karolinska Institutet in the Journal of the National [...]
Researchers highlight five pathways through which microplastics can harm the brain
Microplastics could be fueling neurodegenerative diseases like Alzheimer's and Parkinson's, with a new study highlighting five ways microplastics can trigger inflammation and damage in the brain. More than 57 million people live with dementia, [...]
Tiny Metal Nanodots Obliterate Cancer Cells While Largely Sparing Healthy Tissue
Scientists have developed tiny metal-oxide particles that push cancer cells past their stress limits while sparing healthy tissue. An international team led by RMIT University has developed tiny particles called nanodots, crafted from a metallic compound, [...]
Gold Nanoclusters Could Supercharge Quantum Computers
Researchers found that gold “super atoms” can behave like the atoms in top-tier quantum systems—only far easier to scale. These tiny clusters can be customized at the molecular level, offering a powerful, tunable foundation [...]
A single shot of HPV vaccine may be enough to fight cervical cancer, study finds
WASHINGTON -- A single HPV vaccination appears just as effective as two doses at preventing the viral infection that causes cervical cancer, researchers reported Wednesday. HPV, or human papillomavirus, is very common and spread [...]
New technique overcomes technological barrier in 3D brain imaging
Scientists at the Swiss Light Source SLS have succeeded in mapping a piece of brain tissue in 3D at unprecedented resolution using X-rays, non-destructively. The breakthrough overcomes a long-standing technological barrier that had limited [...]
Scientists Uncover Hidden Blood Pattern in Long COVID
Researchers found persistent microclot and NET structures in Long COVID blood that may explain long-lasting symptoms. Researchers examining Long COVID have identified a structural connection between circulating microclots and neutrophil extracellular traps (NETs). The [...]
This Cellular Trick Helps Cancer Spread, but Could Also Stop It
Groups of normal cbiells can sense far into their surroundings, helping explain cancer cell migration. Understanding this ability could lead to new ways to limit tumor spread. The tale of the princess and the [...]
New mRNA therapy targets drug-resistant pneumonia
Bacteria that multiply on surfaces are a major headache in health care when they gain a foothold on, for example, implants or in catheters. Researchers at Chalmers University of Technology in Sweden have found [...]
Current Heart Health Guidelines Are Failing To Catch a Deadly Genetic Killer
New research reveals that standard screening misses most people with a common inherited cholesterol disorder. A Mayo Clinic study reports that current genetic screening guidelines overlook most people who have familial hypercholesterolemia, an inherited disorder that [...]
Scientists Identify the Evolutionary “Purpose” of Consciousness
Summary: Researchers at Ruhr University Bochum explore why consciousness evolved and why different species developed it in distinct ways. By comparing humans with birds, they show that complex awareness may arise through different neural architectures yet [...]
Novel mRNA therapy curbs antibiotic-resistant infections in preclinical lung models
Researchers at the Icahn School of Medicine at Mount Sinai and collaborators have reported early success with a novel mRNA-based therapy designed to combat antibiotic-resistant bacteria. The findings, published in Nature Biotechnology, show that in [...]
New skin-permeable polymer delivers insulin without needles
A breakthrough zwitterionic polymer slips through the skin’s toughest barriers, carrying insulin deep into tissue and normalizing blood sugar, offering patients a painless alternative to daily injections. A recent study published in the journal Nature examines [...]
