Cannabinoids

Using powerful 7-Tesla brain imaging, researchers mapped how the brainstem manages pain differently across the body. They discovered that distinct regions activate for facial versus limb pain, showing the brain’s built-in precision pain control system. The findings could lead to targeted, non-opioid treatments that use cannabinoid mechanisms instead of opioids, offering safer pain relief options. Key Research Findings Mapping the Brain's Hidden System for Pain Researchers at the University of Sydney have revealed a brainstem network that manages pain differently depending on where it occurs in the body. Using placebo pain relief, they discovered a map-like system that fine-tunes pain control for specific regions, such as the face, arms, or legs. The findings could lead to safer and more precise pain therapies that avoid the risks of opioid-based treatments. The brainstem functions as the main communication pathway between the brain and spinal cord, directing signals that control thought, sensation, and survival responses. It also produces most of the brain's vital neurochemicals, making it a central hub for regulating both physical and emotional states. Published in Science, the study used 7-Tesla functional magnetic resonance imaging (fMRI) (one of the most advanced brain scanners available, with only two in Australia) to identify how two major regions of the brainstem coordinate pain relief through placebo responses. Dr. Lewis Crawford, lead author and research fellow at the School of Medical Sciences and the Brain and Mind Centre, explained, "This is the first time we've seen such a precise and detailed pain map in the human brainstem, showing us that it tailors pain relief to the specific part of the body that's experiencing it." This breakthrough builds on decades of research led by co-author Professor Kevin Keay, Deputy Head of the School of Medical Sciences, who has long studied the brain's role in pain regulation. How the Placebo Effect Reveals the Brain's Pain Control To explore how the brain organizes pain relief, researchers tested 93 healthy volunteers by applying heat to different parts of their bodies. A placebo cream was used on some areas, but scientists secretly lowered the temperature to convince participants that the cream was reducing pain. Each participant's heat level was personalized to reach a moderate level of discomfort, based on a scale from 0 (no pain) to 100 (worst pain imaginable), typically between 40 and 50 degrees Celsius. When the same heat stimulus was later reapplied, participants continued to feel less pain in the areas where the placebo cream had been used, even though the temperature was no longer reduced. About 61 percent reported this effect, a strong indication of genuine placebo-driven pain relief. Dr. Crawford noted, "We found that upper parts of the brainstem were more active when relieving facial pain, while lower regions were engaged for arm or leg pain." Pinpointing the Brain's Pain-Relief Centers Two major brainstem regions, the periaqueductal grey (PAG) and the rostral ventromedial medulla (RVM), were identified as central to this system. Each showed distinct patterns of activity depending on where the pain occurred. Upper sections of the PAG and RVM responded to facial pain, while lower sections activated for pain in the limbs. According to Dr. Crawford, "The brain's natural pain relief system is more nuanced than we thought. Essentially, it has a built-in system to control pain in specific areas. It's not just turning pain off everywhere; but working in a highly coordinated, anatomically precise system." A Blueprint for Targeted Pain Therapies Understanding which brainstem areas are linked to different parts of the body may open new avenues for developing non-invasive therapies that reduce pain without widespread side effects. "We now have a blueprint for how the brain controls pain in a spatially organized way," said Professor Luke Henderson, senior author and Professor in the School of Medical Sciences and the Brain and Mind Centre. "This could help us design more effective and personalized treatments, especially for people with chronic pain in a specific area of their body." The study also challenges long-held assumptions about how placebo pain relief works. Instead of relying on the brain's opioid system, experts say a different part of the brainstem -- the lateral PAG -- is not only responsible but works without using opioids and could instead be linked to cannabinoid activity. "Opioid-based pain relief typically activates central areas of the brain and can affect the whole body, whereas the cannabinoid circuit that we identified appears to operate in more targeted regions of the brainstem," said Dr. Crawford. "This supports the idea that cannabinoids may play a role in localized, non-opioid pain control." "Knowing exactly where pain relief is happening in the brain means we can target that area or assess whether a drug is working in the right place," said Dr. Crawford. "This could lead to more precise treatments for chronic pain that don't rely on opioids and work exactly where the brain expects pain relief to occur -- a huge step forward for pain management."