UC Davis Researchers Seek To Develop a Non-Addictive, Monthly Painkiller
During the pandemic, doctors employed infusions of monoclonal antibodies (lab-made antibodies) to help patients fight COVID-19 infections. University of California, Davis researchers are now attempting to develop monoclonal antibodies that may aid in the treatment of chronic pain. The objective is to create a monthly non-addictive pain medication that can be used instead of opioids.
The project is led by Vladimir Yarov-Yarovoy and James Trimmer, professors in the Department of Physiology and Membrane Biology at the UC Davis School of Medicine. They’ve established an interdisciplinary team that includes several of the same experts that are working on turning tarantula venom into a pain medication.
A model of a complex protein that may fit into nerve channels and stop the transmission of pain. Credit: Phuong Tran Nguyen, UC Davis
Yarov-Yarovoy and Trimmer were awarded a $1.5 million grant earlier this year by the National Institutes of Health’s HEAL Initiative, a determined effort to hasten the development of scientific solutions to the country’s opioid crisis.
People can become addicted to opioids due to chronic pain. According to the CDC National Center for Health Statistics, there will likely be 107,622 drug overdose deaths in the US in 2021, up from an expected 93,655 deaths in 2020.
“Recent breakthroughs in structural and computational biology — using computers to understand and model biological systems — have set the stage for applying new approaches to create antibodies as superior therapeutic candidates to treat chronic pain,” said Yarov-Yarovoy, the principal investigator for the award.
“Monoclonal antibodies are the fastest growing sector of the pharmaceutical industry and have many advantages over classical small molecule drugs,” Trimmer said. Small molecule drugs are drugs that can easily enter cells. They are widely used in medicine.
Trimmer’s lab has created thousands of different monoclonal antibodies for various purposes over many years, but this is the first attempt to generate antibodies aimed at pain relief.
Monoclonal Antibodies Are Already Being Used for Migraine
Although it may seem very futuristic, the Food and Drug Administration has already approved monoclonal antibodies to treat and prevent migraine. These new medications act on a migraine-associated protein called calcitonin gene-related peptide.
The project at UC Davis has a different target—specific ion channels in nerve cells known as voltage-gated sodium channels. The channels are like “pores” on the nerve cell.
During the pandemic, physicians used infusions of monoclonal antibodies to help patients fight off COVID-19 infections. Now, in response to the U.S. opioid crisis, researchers at UC Davis are trying to create monoclonal antibodies that can help fight chronic pain. The research is funded by a $1.5 million grant from the National Institutes of Health’s HEAL Initiative. Credit: UC Davis Health
“Nerve cells are responsible for transmitting pain signals in the body. Voltage-gated sodium ion channels in nerve cells are the key transmitters of pain,” explained Yarov-Yarovoy. “We aim to create antibodies that will bind to these specific transmission sites at the molecular level, inhibiting their activity and stopping the transmission of pain signals.”
The researchers are focused on three specific sodium ion channels associated with pain: NaV1.7, NaV1.8 and NaV1.9.
Their goal is to create antibodies that can fit into each of these channels like a key into a lock. This targeted approach is intended to stop the channels from sending pain signals but not interfere with other signals sent through the nerve cells.
The challenge is that the structures of the three channels they are attempting to block are incredibly complex.
Software Programs Help Create Virtual Models
To address this, they are turning to software programs called Rosetta and AlphaFold. With Rosetta, the researchers are designing complex virtual models of proteins and analyzing which ones might best fit the NaV1.7, NaV1.8, and NaV1.9 nerve channels. With AlphaFold, the researchers independently validate proteins designed by Rosetta.
Once they identify several promising proteins, they will create antibodies that can then be tested on lab-created neural tissue. Human testing would be years away.
But the researchers are excited by the potential of this new approach. Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and acetaminophen must be taken several times per day to relieve pain. Opioid pain medications are often taken daily and run the risk of addiction.
Monoclonal antibodies, however, can circulate in the bloodstream for more than a month before they are eventually broken down by the body. The researchers anticipate that the patient would self-inject the monoclonal antibody pain medication once a month.
“For patients with chronic pain, that’s exactly what you need,” Yarov-Yarovoy said. “They experience pain, not for days, but weeks and months. The expectation is that the circulating antibodies will be able to provide sustained pain relief for weeks.”
The study was funded by the National Institutes of Health.
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8 Comments
I have Addisons disease but also due to a sprained ankle in May 2019 and my gp reluctance to do mri I have been bedridden for four years can’t stand or walk at all on zomorph and oramorph and pregabalin and amitryptyline not making much difference plus all the machines I’ve bought ultrasound etc had a ligothaine infusion after 5 weeks hadn’t worked I rang to be told can’t have next one as government had withdrawn funding after seeing another consultant showed me my last report that said postponed not cancelled so had to go to back of queue next app 5 Jan 2023. The report I received was like a fairy story and appeared not even to be about me so many irregularities. I assume a long day and the physiotherapist who wrote it just threw it together before he went on annual leave. I had been led to believe he was the consultant he wasn’t. Physio is no good for me torn ligaments on knees and ankle and fluid I’ve been trying for 4 years to get pain relief and trying to get alternatives to opiates the meds I’m on I assume are used for palliative care cancer patients. Gp out of their remit and can’t be bothered or care that I’ve been left alone bedridden for so long
I have chronic pain with my back pain with my degradation dice disease and arthritis 20 years got all ingestion on morphine tablets and solfdol and pain patch nothing is working for me I need help please there has to be something to help me with this pain
I am 62. I had a stroke 15 years ago 2 years post I started having debilitating pain on the stroke side of my body thought I was going crazy They told me it was Thalamic Pain Syndrome we tried the Lyrica other Pain non narcotics medicine have been to three pain clinics and they all said there was nothing they could do after 13 years we found a cocktail that worked very well Now we recently moved to Louisiana and have had to start all over again because they don’t want a druggie for a patient they did send the pharmacy and put a new script but the pharmacy is now jerking me around all the illicit use they lump us together I just want to live what life I have left without so much pain
If someone is going to abuse their medication, they will abuse other substances as well. The medication is not the problem. Drug abuse is a mindset, and merely a symptom of a bigger problem. Those who would take their medication responsibly should not have to suffer for the actions of someone else. If opioid medications improve the overall quality of life and sense of well-being for responsible individuals, they shouldn’t be banned on the basis of being potentially addictive. How many other medications does the body become dependent upon, but aren’t restricted? Medical treatment should be individualized, tailored to the specific patient. Demonizing opioids will not resolve the issue of drug abuse. Drug abuse is a cultural problem, that is cross cultural, as in the desire to alter the mind/body with any substance is by and large due to the epidemic of depression in this and many other countries. The individual who abuses any type of substance is either attempting to self medicate for depression and or anxiety, or the lifestyle of drug abuse has been modeled for them within their particular circle of family and friends as a way to relieve stress and bring about an artificial sense of well-being. It seems that all are going about trying to solve the problem of drug abuse in reverse. We know that traditional forms of addiction treatment are by and large ineffective, with a 90% relapse rate. Restricting access to opioids is clearly not working. It merely drives the individual to move on to another substance of abuse, while simultaneously depriving responsible people from obtaining a medication that improves their perceived quality of life. Someone needs to develop a new approach. Sadly, if this pain blocking medicine becomes approved, many who have been prescribed opioids for pain management will find relief for pain but likely be cut of off their opioid medication and the effect on the brain will be some form of depression, and that will have to be addressed, most likely by means that are ineffective in the wake of long-term opioid treatment considering how opioids affect the brain. The patient will be trading one “problem” for another. Until depression and anxiety the medical as well as non-medical causes for depression and anxiety (lifestyle, culture, the economy, etc.) are improved upon, I dare say eliminated (as if that’s actually possible) then there will ALWAYS be substance abuse. Restricting access to those who need opioids has not, and will not solve the problem.
If opioid medications (and drugs in general) are mostly abused as a means of alleviating some form of mental dissatisfaction/emotional deficit, why couldn’t the drug companies find some way to harness the active components in these commonly abused substances in a way that safely treats depression, anxiety, etc? People do what works for them, if it didn’t work, they wouldn’t do it. It’s sad but true that people have a tendency to self-medicate and likely because the depression medications on the market are only temporarily effective. And I agree, in the case of people who use or abuse drugs, that those type people are going to find something else to get messed up and possibly overdose on. The overdose rate has got worse, not better.
I totally agree with the been there done that comment. Been on same dose of my pain meds for 25+ years. 5 taje as prescribed and get relief. We’re grouped on with people who ate doing heroin, fentanyl.. drugs lije that. let us with clean U.A and no call in early for refills aline. We’re doing what the doctor tells us. Leave me be!!! Dont judge me bc im5 on pain medicine, I’m only human, but also keep control of my meds.
I totally agree with Been There Done That. Ive managed to stay on same dose of my painmeds for 25+ years. Dont group me with heroin and fentanyl abusers. We who play by the rules should not be penalized bc we manage our meds. Thank you
Totally agree with been there done that. I have a friend using opiods and she will not over use the medicine for fear of becoming addicted. I use barbiturates for migraines and will not over use them either. Over using meds is contrary to its benefits and the body gets used to the drug so much that eventually it doesn’t do the job of mitigating pain.