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Medscape
15-07-2025
- Health
- Medscape
Why Acute Pain Can Be So Intense for Some and Not Others
Pain is a universal experience, but how it's felt and for how long can vary dramatically from person to person. For some, a surgery or herniated disc is a temporary agony that fades with time. For others, pain can become a chronic, debilitating condition, lingering long after an injury has healed. Scientists are working to understand this complex phenomenon, and new research suggests why some individuals experience pain differently. Our experience of pain relies on a complex network of nerves known as the pain neuroaxis. This system involves both peripheral nerves (those outside the brain and spinal cord) and central neurons (those in the brain, brainstem, and spinal cord). When you feel pain, these neurons fire, sending signals along this pathway to your spinal cord and brain. Many regions of your brain then interpret these signals as pain. 'Acute pain is beneficial to protecting our bodies, but chronic pain often serves no purpose and outlives its initial purpose and represents a dysfunction,' noted Steve Davidson, PhD, associate director of NYU's Pain Research Center, New York City. Scientists are still learning why normal acute pain sometimes transforms into abnormal chronic pain. New research published in Science Advances challenges a long-held belief: it's not always more neuronal stimulation that causes pain. Instead, the balance between activation and repression in specific neurons is crucial for a normal pain experience. A Surprising 'Volume Control' for Pain This new research focuses on specific neurons called projection neurons found in part of the brainstem called the medullary dorsal horn. These neurons are crucial relay stations, sending pain messages to other parts of the brain, like the parabrachial nucleus, which is involved in processing emotions and motivation alongside pain. To study pain, researchers used mice. For acute pain, they exposed mice to bright ultraviolet light, similar to how a bright light can cause discomfort in your eye at the optometrist. For chronic pain, a loose stitch was tied around the trigeminal nerve below the eye, mimicking a migraine-like pain. Interestingly, during the peak of acute pain, these pain-relay projection neurons became less excitable, explained Alexander Binshtok, PhD, professor in pain research at the Hebrew University of Jerusalem, Jerusalem, Israel, and an author of the study. It's as if their 'volume control' was turned down, causing them to fire fewer signals to the brain even though the pain stimulus was strong. As the mice's behavior indicated they were no longer experiencing pain, the excitability of these neurons returned to normal. After 20 years in the pain field, Binshtok reflected on the long-standing paradigm that pain is linked to increased nerve activity. 'What was surprising is that when we have inflammatory pain, some of the neurons actually decrease the activity in a way to control the level of pain,' he said. Using electrophysiology and computer modeling, the researchers traced the mechanism behind this 'volume control' to an increase in the neuron's potassium A-current (IA). This current acts as a brake on the neuron's activity — when IA increases, it makes it harder for the neuron to fire. This suggests a built-in protective mechanism that helps regulate the intensity of acute pain and prevents the system from being overwhelmed. As Binshtok explained, 'If suddenly these mechanisms are not working, every input from the periphery will be amplified.' The Shift to Chronic Pain The picture changes dramatically when pain becomes chronic. In the mice experiencing long-term pain, researchers observed no such increase in the IA. Instead, these same medullary dorsal horn neurons showed increased excitability and firing. It's as if the protective 'brake' is missing or not working effectively. This suggests a critical difference in how our bodies handle acute vs chronic pain. In acute pain, there appears to be a natural system that helps tune down the pain signals. But if this system isn't functioning properly, or if this tuning mechanism is absent, it could contribute to pain becoming a persistent problem. Davidson summarized the finding that there is a mechanism to reduce activity during acute pain but not in chronic pain with an analogy: 'It's like automatic braking when you are driving too fast in the city — but this mechanism is disabled on the highway, during chronic pain.' Binshtok noted that while it seemed surprising for a neuron to decrease its activity when bombarded with input at first, 'apparently this is not a surprising phenomenon when we look at other systems like the hippocampus or cortex, this adaptation is pretty common.' And this is the first time, Binshtok said, that the same neurons were shown to respond differently in acute vs chronic pain. Looking Ahead The ultimate goal in pain research, noted Patrick Sheets, PhD, associate professor of pharmacology and toxicology at the Stark Neurosciences Research Institute at Indiana University School of Medicine, Indianapolis, is to develop 'some sort of small molecule that then would eliminate aspects of pain that we don't want while preserving the ability of the person to function normally without being overwhelmed by something like addiction or lethargy.' And ultimately, it may be that pain treatment will need a personalized approach. Sheets noted that certain drugs may end up working depending 'primarily on what type of pain you have, and that can be challenging — understanding what sort of pain people are going through, diagnosing it, and then understanding what's happening at the cellular and circuit level so that you can hopefully intervene.' However, whether this IA-driven mechanism could provide relief for chronic pain sufferers is still a long way from being realized. For one thing, the study did not identify the specific potassium channel responsible for changes in IA current, Sheets noted. Davidson also pointed out that, 'ideally, the IA effect would be reversed or blocked experimentally to block the behavioral effect.' Without that, he noted, we don't know whether the increased IA current is the true cause of the change in pain behavior. Additionally, the study focused on male mice — in female mice, they did not observe the same sensitivity to ultraviolet light. Sheets noted that he has also observed sex-linked differences in his own mouse studies. (There is evidence that men and women experience pain differently as well.) And Binshtok noted that even if they find the IA target that could potentially regulate chronic pain in mice, they would still need to confirm the mechanism in humans. There's still a lot left to learn. However, Davidson said, 'Certainly looking into the IA current now looks like a promising avenue for exploration.'
Jordan News
25-03-2025
- Health
- Jordan News
Non-Surgical Treatments Are Not Very Effective for Lower Back ...
اضافة اعلان Acetaminophen pills, acupuncture, massage, muscle relaxants, cannabinoids, and opioids—these are a list of treatments available for long-term lower back pain. However, there is no strong evidence that these treatments actually relieve pain, according to a new study that summarized the results of hundreds of randomized trials, as written by Nina Back Pain Lower back pain affects an estimated one in four American adults and is the leading cause of disability globally. In most diagnosed cases, the pain is 'nonspecific,' meaning there is no clear cause, which partly contributes to the difficulty in treating of Non-Surgical Treatments In the study published this month in BMJ Evidence-Based Medicine, researchers reviewed 301 randomized trials comparing 56 non-surgical treatments for lower back pain, such as medications and exercises, against placebos. The researchers used statistical methods to combine the results of these studies and draw conclusions, a process known as a of Ibuprofen and Aspirin The researchers found that only one treatment, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and aspirin, was effective in relieving short-term or acute lower back Treatments with Little Benefit Meanwhile, five other treatments showed sufficient evidence of being good for relieving chronic lower back pain, though the benefit was small. These treatments included: exercise, spinal manipulation as performed by a chiropractor, lower back patches, antidepressants, and creams that provide a warming sensation. However, the benefits were Davidson, Associate Director of the Pain Research Center at New York University, who did not participate in the study, said: 'The key takeaway from this study is that lower back pain is extremely difficult to treat. There are some treatments that were found to be effective, but those that were effective had minimal clinical benefit.'For example, there was strong evidence that exercise could reduce chronic back pain, but it only reduced pain intensity by an average of 7.9 points on a 0-100 pain scale, which is less than what most doctors consider a clinically significant Prasad Shervalkar, Assistant Professor of Pain Medicine at the University of California, San Francisco, said: 'Let's say a patient rates their pain as a 7 out of 10. If I told you, 'What if I could get you to a 6.3 out of 7?' Wouldn't that be great? Not really. And that's the size of the effect.'Dr. David Clark, Professor of Anesthesia at Stanford University School of Medicine and pain specialist at the Palo Alto Medical Center, said the results align with his experience as a practitioner. He added: 'Most of what we try doesn't work with patients.'Providing 'Moderate Relief' However, he and other experts stressed that the study confirmed some common treatments could provide moderate example, Shervalkar said there are many types of NSAIDs, and they may not be used sufficiently. He added: 'People may try two or three types and suffer side effects, but doctors don't try others.'Exercise Eases Pain Although the effect size of exercise was small, doctors still believe it likely helps alleviate back pain in the long term. Shervalkar said core exercises, like planks, help strengthen the muscles supporting the spine. Clark added that exercise has benefits beyond reducing pain intensity, such as improving strength, mobility, mood, and reducing the impact of pain on task Cashin, lead author of the study and Deputy Director of the Pain Impact Center at the Neuroscience Research Center in Australia, said the goal of the study was to identify initial treatments for lower back pain that have effects beyond placebo, which may warrant further study and those that do not. For example, there was strong evidence that paracetamol (acetaminophen) was not effective in treating acute lower back study included a long list of treatments for which the evidence was 'uncertain' due to a low number of participants or potential significant bias in the confirmed that this does not necessarily mean these treatments are ineffective. One flaw of the type of analysis Cashin conducted was that it pooled data from different studies and populations to simulate one large-scale trial. But in this process, a strong signal from one study about the effectiveness of a treatment might be drowned out by noise from studies that were perhaps not well designed, according to Massage, and Acupuncture For example, the review found that the evidence for interventions like heat (using a heating pad), massage, and acupuncture was of low certainty, but these treatments reduced pain intensity by about 20 said the evidence for treatments like heat might be inconclusive, but they still recommend patients try it. Shervalkar said: 'It's cheap; it's available; it almost doesn't cause any harm.'Davidson said treatments with inconclusive evidence represent a starting point for further research. He added: 'What this list shows is that we have potential to work with regarding exploring different ways to treat lower back pain.'New York Times Service
