Scientists Find New Link in Solving the Puzzle of Complex Regional Pain Syndrome

Sometimes after trauma (even minor trauma) to human tissue, a chronic pain condition develops. Once called i>reflex sympathetic dystrophy (RSD), this syndrome is now referred to as complex regional pain syndrome (CRPS).

With CRPS, the pain generated is greater than expected for the degree of tissue trauma that has been sustained. The pain begins early on and spreads from a small, local area to a larger, regional distribution. Patients report a burning sensation that comes on suddenly for no apparent reason. It is intense. Usually, there are other symptoms such as sweating, hair growth, and changes in skin color and texture.

No one knows for sure what causes this to happen. Lab studies of blood and tissue samples appear normal. There is no apparent inflammation of the affected soft tissues (e.g., skin, muscles). There is some evidence that the cellular changes are occuring within the nerve fibers to the affected tissues. Most of what we’ve learned so far has come from animal studies.

Scientists have been able to produce a similar response in rats by causing a bone fracture in such a way as to set up a CRPS response. By doing so, they can then study the tissues to see what’s going on inside the body. The hope is to be able to work their way back to identify causative factors. Then it might be possible to prevent those from happening. In that way, we could prevent CRPS from developing in susceptible people.

In this editorial, two scientists (one American, one German) team up together and report the results of their efforts with this CRPS-induced (animal) fracture model. They report that it looks like it may be possible to inhibit the over reaction of the neurogenic inflammatory process by using a substance to inhibit the release of substance-P.

Substance P is a neuropeptide that acts as a messenger of information in the nervous system. Substance P is released from the ends of specific sensory nerves. It seems to be able to increase the excitability of pain responsive neurons. That may answer some of the questions about why people develop so much pain, but it doesn’t answer the question of why those particular people have this pain response after an injury.

Looking at patients with CRPS as a whole, it has been noticed that these same individuals often have migraine headaches, too. There is a signaling neuropeptide called CGRP that seems to be linked with the overly dramatic nerve response in both migraine headaches and complex regional pain syndrome. This piece of the puzzle supports the idea that there’s a nerve inflammation response going on that the body just can’t seem to regulate.

With this much new information, scientists are back to the drawing board. Now they are trying to understand why there might be a loss of inhibition in the complex cascade of nerve-related inflammatory chemicals. The fact that this response can occur after major or minor trauma suggests it’s not the trauma itself that exaggerates the process, but rather, something has gone haywire in the nervous system’s response to injury.

Each new finding brings us closer to solving the painful puzzle of complex regional pain syndrome — a solution that could bring welcome relief to chronic pain sufferers from this very disabling condition.