March 3, 2013


Producing Chronic Pain in the Peripheral Nervous System

When you stub a toe, maybe you curse and grab your hurt foot, while hopping up and down on the other foot. If you reflect on what you felt, you’ll find that you experienced two distinct pain sensations. First, A-Delta fibers gave you immediate feedback that you hurt yourself once again by stubbing your toe on that same table leg that hasn’t moved since the last time you bumped into it. (Maybe now is a good time to move it!) The input from these sensory nerves may even have been fast enough to help you reduce the force that you applied to the poor toe.

Second, you likely felt a later pain sensation from C fibers that didn’t seem all that useful. The late C fiber pain is the one that causes you to curse the table that hurt your toe. This delayed pain from an injury tells you about the severity of the injury and motivates you to do something about it. For example, it keeps you from injuring the toe further by continuing to walk or run around while the pain is active. Scientists have rigorously studied how injuries generate pain that persists until healing is complete. This form of pain, known as acute pain, is understood by most people as “par for the course” for minor injuries. How long the pain lasts depends on how much force was involved, whether or not you broke your toe, and so on.

Chronic pain is a very different story. Even if an injury appears to have healed, a variety of adaptations of the body to the injury can set in motion changes that result in chronic pain. Some of these attempts of the body to deal with injury can go wrong and are important for understanding why chronic pain can develop. Injury to your body sets in motion your immune system, which is your body’s defense system against disease and injury. In turn, your immune system mobilizes inflammation. A staggering array of inflammatory cells are released at and near the injury, and nociceptors (especially C fibers) are uniquely able to respond to these chemicals. A slight stub of a toe protected by a shoe yields a low level of inflammation that clears up quickly. A forceful stub of a bare toe in the dark turns the toe lovely shades of purple and causes swelling and sensitivity for a few days.

Here’s where things get interesting. It turns out that when C fibers respond to pain, they also turn on inflammation, which itself is another source of pain. In other words, pain begets more pain. As long as you have inflammation, you have activity in nociceptors and vice versa. This process is the culprit behind some types of chronic pain, which is like a stubbed toe with endless inflammation.


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