Why pain feels emotional: New brain pathway linked to suffering

Even a brief jab from a pin or the sting of a hot pan can leave behind pain that lingers as dread, worry, and distress. Researchers have now pinpointed a strand of nerve cells that splice those emotions onto raw sensation.

The research was conducted at the Salk Institute for Biological Studies, where neuroscientist Sung Han and his colleagues mapped this pathway in mice. The findings show how a spinal spark becomes both a sharp twinge and a wave of misery.

By isolating calcitonin gene-related peptide (CGRP) neurons in a small pocket of the thalamus and tracing their links to the amygdala, the team made a key discovery. They showed that this branch of the classic spinothalamic tract carries the feelings that make pain matter.

The emotional triggers of pain

For decades, the prevailing view was that the brain processes sensory and emotion-related aspects of pain through separate pathways.

“But there’s been debate about whether the sensory pain pathway might also contribute to the emotional side of pain,” Han said. “Our study provides strong evidence that a branch of the sensory pain pathway directly mediates the affective experience of pain.”

In other words, the same “highway” that delivers information about heat or pressure can fork into lanes that deliver pain feelings.

Rewriting the pain textbook

Textbooks have long split pain in two. Fast sensory signals climb the spinothalamic tract to the thalamus. From there, they travel to the sensory cortex, letting you spot where you were burned and how hot it was.

A second route – the spinoparabrachial tract – was said to feed emotion and shock to the brainstem.

The Salk findings blur that distinction. By injecting tracers into the spinal cords of mice, the team followed some spinothalamic fibers to the parvocellular subparafascicular nucleus of the thalamus.

This region is home to CGRP-tagged neurons that wire straight to the amygdala, the hub for fear and anxiety.

Turning emotion on and off

To test what the cells do, researchers genetically silenced the CGRP neurons. Mice still withdrew from a hot plate or pinprick, proving that sensory detection was intact. However, they stopped avoiding places where that discomfort had occurred.

When the same neurons were flicked on with light-driven optogenetics, the animals avoided the chamber even though no pain stimulus was present, a sign of pure emotional distress.

“Pain processing is not just about nerves detecting pain; it’s about the brain deciding how much that pain matters,” said first author Sukjae Kang.

“Understanding the biology behind these two distinct processes will help us find treatments for the kinds of pain that don’t respond to traditional drugs.”

Pain beyond the wound

Many difficult disorders – fibromyalgia, migraine, and some forms of post-traumatic stress – feature overwhelming pain or threat without obvious tissue injury.

Gene expression analysis showed that thalamic CGRP neurons carry several signatures already linked to migraine. Drugs that block CGRP are already easing migraine attacks in clinics.

Han’s team suggests these drugs could calm the thalamic circuit that turns everyday bumps and sounds into agony.

“Our discovery of the CGRP affective pain pathway gives us a molecular and circuit-level explanation for the difference between detecting physical pain and suffering from it,” Han said.

“We’re excited to continue exploring this pathway and enabling future therapies that can reduce this suffering.”

Making pain more treatable

Everyone feels the initial jab at roughly the same stimulus strength, yet people vary wildly in how long they brood over it. The new work shows that variation may begin inside the thalamus, not only in higher thought centers.

By revealing a precise set of neurons that add the emotion behind the pain, the study opens the door to therapies that dull suffering without muting essential warning signals.

Clinicians could one day pair CGRP blockers with behavioral therapy to restore a balanced response to hurt.

Looking beyond physical hurt

The Salk team now plans to trace the same circuit in other species and to test whether it reacts to social pain such as heartbreak or grief.

If the CGRP loop proves to be a general “alarm” network, dialing it down might help people whose brains stay locked in high alert after trauma.

For the millions living with chronic pain, the discovery offers concrete hope that scientists can uncouple sensation from suffering. It could let a simple bruise heal without haunting the mind.

The study is published in the journal Proceedings of the National Academy of Sciences.

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