Smash or Burn: How Our Body Distinguishes Pain

We have all encountered pain, but not all pain feels the same. Crushing your hand in a car door feels nothing like the burning sting of a hot stove. A new study suggests that the spinal cord can distinguish different types of pain before the brain even knows you are hurt. In fact, certain spinal cord nerves may also influence how intensely pain is felt. Their findings in mice could pave the way for more targeted treatments, especially for those living with chronic pain.

Pain comes in different forms. Sometimes, it is a sharp, stabbing feeling that comes on suddenly, like when you cut your finger or break a bone. Other times, it is a more gradual tingling sensation or radiating pressure. Regardless of how and where you feel it, pain is your body’s way of letting you know something is wrong.

Special receptors, called nociceptors, send the first warning signals. These tiny sensors are embedded throughout the body in our skin, muscles, joints, and internal organs. Some receptors react to extreme temperatures, like when you touch something hot or step into icy water. Others respond to physical force or injury. We also have receptors that detect chemical changes, like with inflammation.

Signals from these receptors travel through the spinal cord to reach the brain. This process happens almost instantaneously, allowing your brain to pinpoint where it is coming from and decide how to respond. However, sometimes, your body reacts before you even have a chance to think about it. Think back to a time when you touched something hot and your hand instantly pulled away. This reflex is generated in your spinal cord. Before the signals go all the way up to the brain, nerves in the spinal cord send an immediate message to your muscles, directing you to pull your hand away.

The spinal cord is not just an intermediate stop before signals reach the brain. This study suggests that the nerves in the spinal cord play an active role in processing these signals. How we experience pain seems to be shaped here before the brain even gets the full message.

A Mouse Study of Heat Versus Physical Pain

This discovery was made while observing how adult mice respond to heat-induced versus physical pain. While the animals slept under anesthesia, the team dipped the mice’s paws into hot water. For another group of mice, pressure was applied to their paws to simulate a pinch or squeeze.

Before these experiments began, the team injected each mouse with a special virus that acts like a genetic highlighter. This gene-editing tool tracks how neurons activate under each condition. They found that heat-induced versus physical pain recruits different nerve groups in the spinal cord. These distinct pathways may be how the brain tells one kind of pain from another.

When they artificially activated these neural circuits, the team discovered that they could control the animals’ behaviors. This time, they used light pressure and warm (but not painful) water. When the matching neural network was activated simultaneously, the mice responded by shaking or licking their paw to relieve the pain. When these nerves were silenced, the animals did not react. These findings suggest that specific neurons in the spinal cord may play a direct role in how we experience different types of pain.

The Role of Galanin Neurons

Within these neural networks, there seems to be a special class of nerves called galanin (Gal+) neurons that further control how pain signals are processed. Activating these neurons releases a neurotransmitter that calms down nerve activity and blocks pain messages from reaching the brain. If these messages do not reach the brain, it changes how we perceive pain.

Using clozapine, a drug that is often used to treat schizophrenia, the team found that blocking these neurons made the animals more sensitive to both heat-induced and physical pain. Enhancing their activity, on the other hand, numbed their reaction. The team speculates that galanin neurons in the spinal cord act as a brake on pain. The stronger the pain signal, the more these neurons are recruited to dampen the intensity of the pain. This helps maintain the body’s threshold for pain.

What they found in mice may help us understand pain like never before. The discovery of pain-specific nerves in the spinal cord could open new possibilities for treating various conditions. By targeting certain nerves directly, we may be able to develop treatments that replace opioids and other painkillers without serious side effects and the risk of addiction. In the future, we may not just manage pain—we could finally outsmart it.