Unlocking the Secrets of Pain and Emotion

Researchers at the Salk Institute have made a groundbreaking discovery, identifying a brain circuit that links physical pain to its emotional impact. This revelation offers hope for treating chronic pain disorders like fibromyalgia, migraines, and post-traumatic stress disorder (PTSD). Published in the prestigious *Proceedings of the National Academy of Sciences* on July 9, 2025, the study sheds light on how our brains perceive pain differently.

Challenging Old Beliefs About Pain Processing

Traditionally, it was believed that the brain processes the sensory and emotional facets of pain through separate pathways. Senior author Sung Han, who holds a significant position at Salk, states, "For decades, there has been a debate on whether the sensory pain pathway contributes to the emotional facets of pain." This new study offers compelling evidence that a specific branch of the sensory pain pathway is directly responsible for the affective experience of pain.

Understanding Pain: The Emotional vs. Sensory Experience

Pain consists of two crucial dimensions: the immediate physical sensation and the emotional discomfort associated with it. While everyone experiences sensory pain similarly, the emotional response varies greatly from person to person. This emotional aspect can lead to disorders if it becomes overly sensitive or prolonged, making it vital to identify which brain mechanisms control these different forms of pain.

Unveiling a New Pathway for Pain Communication

Conventional wisdom held that sensory pain was routed through the spinothalamic tract, which conveys pain signals from the spinal cord to the thalamus before reaching sensory areas of the brain. Conversely, the affective component was thought to travel via the spinoparabrachial tract into the brainstem. However, older research methods hinted at a more intricate pain circuitry.

Utilizing advanced techniques, Han and his team revisited this intriguing question and uncovered a novel spinothalamic pathway in mice. This new circuit sends pain signals to a distinct area of the thalamus connected to the amygdala—the brain's emotional processing hub. Notably, the neurons in this circuit express a specific neuropeptide called CGRP (calcitonin gene-related peptide), initially identified in Ronald Evans' lab at Salk.

The Disturbing Role of CGRP Neurons in Pain Perception

When CGRP neurons were genetically silenced, the mice still reacted to minor pain stimuli, showing their sensory processing remained intact. Yet, they didn’t associate these experiences with lasting negative feelings, lacking any learned avoidance behavior. Conversely, activating these neurons led to signs of distress and learned fear responses, indicating their crucial role in emotional pain processing.

Hope for Chronic Pain and PTSD Treatments

Understanding this pathway could transform treatments for chronic pain conditions that often arise without a clear physical injury or signal. Overactivity in the CGRP spinothalamic pathway may cause the brain to misinterpret or overreact to harmless sensations, a common phenomenon in conditions like fibromyalgia and migraines.

Han notes that some CGRP blockers are already utilized in migraine treatments, hinting they could inspire novel, non-addictive therapies for pain disorders. Additionally, there may be implications for psychiatric issues like PTSD, as the CGRP affective pain pathway appears to contribute to the brain's response to a multitude of unpleasant sensations. This could lead to innovative approaches to alleviate fear and hypervigilance in trauma-related conditions.

A Gateway to New Therapeutics in Pain Management

While the connection between the CGRP pathway and psychological pain from social experiences remains to be explored, its discovery presents a significant breakthrough in understanding pain's emotional dimension. Han concludes, "Our findings pave the way for future therapies aimed at reducing suffering from pain, by exploring the biological basis of these two distinct processes."

The continued research could potentially unlock new avenues for managing chronic pain and enhance the quality of life for millions who suffer from these debilitating conditions.