In January, US Food and Pharmaceutical Administration (FDA) approved The first new painkiller for more than twenty years. The decision was excited throughout the health sector: the drug called Suzetrigine and sold under the Journavx brand is not an opioid.
Opioid painkillers such as oxycodone and morphine are still used to treat severe pain in the UK and the United States. But they come with an obvious disadvantage: the risk of addiction.
Between 1999-2017, the number of overdose deaths containing prescription opioids in the USA ascended According to the National Institute of Drug Abuse, approximately 400% from 3,442 to 17.029. rose According to the National Statistics Office, from 1,332 to 2,551 in 1999.
Pharma companies have been trying to develop safer painkillers since the beginning of the US Opioid crisis. However, these efforts, a Less than 1 % chance It will progress to FDA approval from the phase 1 clinical studies of a new pain drug.
One reason for this is that pain is not a physical phenomenon, but also affected by psychological factors.
Journavx’s success takes a pleasant break from a long setback history, but experts say it’s just part of the puzzle. For beginners, the drug is only available for specific short -term pain types, but there are still many types of pain that still need new treatments.
In addition, the science behind some other types of pain is not clear, which makes it difficult to design treatments for them. And it is a pain rewarding experience. So, whether opioid or not, is there anything like a painkiller that does not do?
What is pain?
When you think of pain, you can imagine that someone prevented the toe. This type of pain – when it damages body tissue – is called nosiseptive pain. At the Department of Cell Biology and Physiology at the University of North Carolina, Associate Professor Grégory Scherrer says that sensory neurons in the damage area called Nosiceptors are activated. Nosiceptors send signals to the spinal cord where other neurons process them.
Then, the signals pass into several parts of the brain in complex ways. Cortex, one of these episodes, is responsible for the processing of sensory information, says Anthony Dickenson, a professor of neuroscience, physiology and pharmacology at the University of London (UCL). Only when this process occurs, we “feel” as the signal pain.
Dickenson is called neuropathic pain – called neuropathic pain – as a result of damage to the nervous system outside the brain and spinal cord. Damaged or defective neurons ignite signals passing through the same procedure. An example is diabetic peripheral peripheral neuropathy, which damages high blood sugar damage to the blood vessels carrying blood to the nerves, resulting in nerve damage and potentially death in extremities.
In general, the perception of pain contains two systems. This is a neural network passing through limbs, organs and other tissues, also known as the peripheral nervous system. Then there is a central nervous system of brain and spinal cord.
The third type is less understood. Notyplastic pain does not contain significant damage to tissues or neurons, but it is thought to be caused by a problem about how the central nervous system works. “Relatively normal stimuli produce pain when they should not do it, Dic says Dickenson. An important example is fibromyalgia, a disorder that affects women.
Jeffrey Mogil, a professor of psychology at McGill University Montreal, believes that some researchers are a thinner or neuropathic pain in which nosiplastic pain is more difficult to detect tissue or nerve damage.
In a medical environment, it is treated according to how long it lasts, says the professor of clinical health psychology in UCL, Amanda Williams. For example, after a injury or operation – which lasts for three months or less – is usually classified as acute, while pain that lasts more than three months is generally considered chronic.
Williams says that the amount of pain that a person feels is not always associated with symptoms of physical damage. For example, while a person could feel a little wear and wear on his knees, another person with more damage would not feel pain.
Is painkiller addictive?
Regardless of the type and length, people are cable to avoid pain. In addition to the cortex, pain signals are traveling to another part of the brain called limbic system, which is responsible for processing emotions, Dickenson says.
This often triggers the feelings of fear, anxiety and depression that accompany the pain. Pain signals also close the dopamine release, a neurotransmitter associated with reward emotions. Mark Hutchinson, Professor of Biomedicic School at the University of Adelaide, says “absolutely rewarding” to get rid of the pain.
But Williams has many experiences that are rewarding without addictive, up to seeing friends. According to Hutchinson, the “switch point ğı in which an award is addicted is defined by damaging a person’s wider health and welfare. Opioid painkillers can turn this key to how they work.
Opioids cut the pain signal by binding and activating the inhibitor opioid receptors in the brain and spinal cord. These receptors form part of the body’s endogenous opioid system that helps regulate pain and mood. However, one of the receptors can increase the dopamine signal between certain parts of the brain when the-μ-opioid receptor is active.
The resulting dopamine casting naturally creates a reward or a sense of pleasure that can be above the rewarding nature. The body may also create a tolerance to opioids over time, ie, the same painkillers or a reward may be required at higher doses of drugs to experience. This forms the basis of addiction.
However, there are many painkillers who do not work in the reward system such as Christopher Eccleston, Paracetamol and Ibuprofen, Professor of Psychology at Bath University. “Is pain relief always addictive? I think the answer is no.”
What are alternatives to opioids?
It was developed by Journavx Vertex Pharmaceuticals and belongs to a class of drugs that block voltage -door sodium channels (VGSCs).
VGSCs allow sodium ions to flow into certain cells of the body. After entering the cells, ions trigger electrical activity – or action potentials that are responsible for a number of body functions from heart beats to pain signal.
Journavx selects a VGSC called NAV1.8, which is predominant in the neurons that detect pain in the peripheral nervous system, says David Altshuler, Vertex’s scientific officer. The drug does not move like opioids on the brain, and instead moves outside the brain, ie there is no risk of addiction.
Vertex did not apply for Journavx approval in the UK. In the USA, the drug is only available for mid to mid -severe acute pain.
Some experts are skeptical about a non -opioid need in acute pain. Scherrer is relatively rare that someone who receives opioid for a few days after an operation a few days after surgery becomes dependent on them. Nowadays, there is more communication about opioid risks, and many patients demand a minimum amount before moving on to another drug.
However, Altshuler estimates that 80,000 people in the United States are given only one for acute pain annually develops an opioid addiction.
Experts agree that there is an important need for non -opioid painkillers in chronic pain. There Small evidence According to NHS, the efficacy of opioids in the treatment of chronic pain, and the use of them in the long term only increases the risk of addiction.
David Anderson, a professor of neuroscience at King’s College London, is treated much less success than chronic pain acute pain. There is a different cause of every chronic pain condition, and in many cases it is not well understood. In order to introduce more than a layer of complications, placebolar is increasingly performance in clinical pain studies in recent years, Moil says, Moil, says research In 2015, it was published as a writer.
A potential explanation for this trend is the presence of a neural circuit in the brain that mediates the perception of pain according to people’s expectations. research Written by Scherrer in 2024. People registered in clinical studies may expect to get rid of pain. “When we wait to alleviate pain, we take circuits that release endogenous opioids in our brain,” Scherrer explains.
In a study on patients with chronic condition called lumbosacral radiculopathy, Journavx produced Reduction of pain in legs similar to placebo. According to Vertex, the drug significantly reduced patients’ pain from their initial level, which was designed to show the experiment. The company added that the placebo branch was included in the “reference”, not for “statistical comparison”.
However, experts were not largely convinced. Mogil, Journavx’s idea for Lumbosacral radiculopathy, seems to be “ridiculous ında in the face of evidence that he does not work better than placebo. Vertex said it plans to design future trials in a way to better control the placebo response.
Another new painkiller species called Jabranopadol is opened for the approval of FDA after successful acute pain has been successful in two late stage clinical work after various operations. The Jabranopadol activates the μ-opioid receptor, but activates the NOSİSEPTIN opioid receptor (NOP). Scherrer, the latter is structured very similar to an opioid receptor, but behaves differently.
According to Tris Pharma, the company behind the Jabranopadol, the activation of the NOP significantly reduces the effects of reward, tolerance and respiratory depression (respiratory or respiratory shallow) associated with μ-opioid receptor activation. The result said it was a painkiller with a similar activity but with a much lower risk.
In what is known as a human abuse potential work, non-independent recreational opioid users were given two types of opioid-oxicodone and trammadol-and cebranopadol to see which they prefer. Ketan Mehta, the General Manager of Tris, says that three active drugs are preferred by Jabranopadol, and that only marginalized placeboya is preferred.
Vertanical, another pharmaceutical manufacturer, recently reported the success of Phase 3 for non-opioid drugs in patients with chronic back pain. The drug contains THC – the active ingredient in cannabis is “high”. The company does not experience poisoning patients because the THC levels in their bodies are not high enough.
Despite all these new pharmaceutical approaches, most experts agree that there is no such thing as a magic bullet for pain. “We will need to treat pain with multiple medications that move in emotion and cognitive not only in the peripheral nervous system, the central nervous system, the brain and not only in sensory systems, S said Scherr. He added that other types of treatment, such as neurostimulation and cognitive behavioral therapy, will also play a key role.
