A new study from Uppsala University in Sweden shows for the first time how the physiological mechanisms of chronic soft tissue pain such as tennis elbow can be explored with the help of PET scans that appear to "light up" activated pain receptors.

Writing about their work in an online issue of PLOS ONE, the researchers describe how they used PET imaging with a radioactive tracer to show clearly visible differences between a painful arm and a healthy arm that correlated with the pain of tennis elbow.

Chronic pain is one of the most common reasons people see their doctor. It is a huge personal and economic burden.

According to a 2011 report from the Institute of Medicine, together with acute pain, chronic pain costs the US economy an estimated $560-635 billion in direct medical costs and lost productivity a year.

Musculoskeletal pain is the most common type of pain - it includes pain associated with bone (such as arthritis), and pain in soft tissue, which by default, is the rest of the body such as muscle, fascia, tendons, ligaments, cartilage and other tissue structures.

But, while soft tissue pain can be just as debilitating as pain from bony structures, because it does not involve bone, it is often overlooked and lacks effective techniques for locating it and diagnosing the underlying causes.

PET imaging and radioactive tracer light up receptor activity

For their study, Magnus Peterson of Uppsala University's Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology, and colleagues, worked with positron emission tomography (PET), an imaging method used in medical diagnoses, and a radioactive tracer that is injected into the bloodstream.

The radioactive tracer is a chemical compound that binds only to a specific type of cell signaling receptor, called NK1, which is known to play a role in pain processes. (When tissue is damaged, there is an increase in a neuropeptide substance called P, that binds to and activates the NK1 receptor.)

Because it is radioactive, the compound "lights up" in the PET scan, showing where it is binding to NK1 in the body.

The team recruited 10 patients with chronic tennis elbow who were being treated with graded exercises.

Before treatment, the PET scans showed that the tracer intensity was higher in the affected arm (it lit up more) than the unaffected arm.

In eight of the patients examined after treatment, the pain ratings fell, but tracer signal intensity only fell in five, and went up in the other three.

The researchers write:

"In conclusion, NK1 receptors may be activated, or up-regulated in the peripheral, painful tissue of a chronic pain condition. This up-regulation does, however, have moderate correlation to pain ratings."

First study to 'visualize' NK1 pain receptors in soft tissue

The study is the first to visualize this activation of NK1 receptors using diagnostic imaging in painful tissue in humans.

When tissue is damaged, the P-NK1 system is more active, and forms part of an interaction among peripheral nerves, immune cells and the tissue itself that seems to help guide the body's own repair process. But in tennis elbow, the P-NK1 activation lingers, and this is what the researchers have managed to visualize, with the help of PET imaging and the marker for NK1.

While the results are promising, this is a small study, and the costs and complications of using PET scans to help diagnose tennis elbow are prohibitive, so other solutions will have to be found before clinical application is feasible.

But it's a start that has opened a new avenue to explore in the diagnosis of chronic soft tissue pain, as Magnus Peterson explains:

"In the future, we hope to be able to develop less expensive markers that enable us to use the method in everyday clinical practice. We also aim to create markers for other physiological processes that we know are active in chronic soft tissue pain."