With CNS involvement, centrally acting analgesics then can have multiple benefits, Dr. Clauw said.
“When someone responds to one of these drugs, they typically have an improvement in more than just pain. If they respond to a serotonin norepinephrine reuptake inhibitor, people will often have improvements in fatigue and in mood,” Dr. Clauw said.
Measuring the Mechanisms of Pain
Understanding the mechanisms of a specific patient’s pain can help direct treatment better, leading to “personalized analgesia,” he said.
Neuroimaging, like functional magnetic resonance imaging (fMRI), is helping in this regard, he said. FMRI allows changes in blood flow to be examined, showing neuronal activation that is associated with various tasks. Positron emitting tomography and H magnetic resonance spectrometry allow the activity of neurotransmitters to be examined.
An emerging interest is the significance of the level of brain “connectivity” among regions not normally connected, Dr. Clauw said.
Experts are now beginning to wonder whether this might be partially responsible for the memory problems and some of the other difficulties seen in people with chronic pain, he said. The pain, it seems, literally might be taking up brain networks needed for executive functions and interfering with those kinds of tasks.
Whether certain therapies work can have everything to do with the mechanism behind the pain, Dr. Clauw said. Opioids, for instance, don’t seem to work very well for centrally regulated kinds of pain.
“This is the reason that we should move towards a mechanistic approach to pain,” Dr. Clauw said. “Because it’s not just academic interest as to what underlying mechanism or mechanisms someone has. It really is going to determine which drugs they’re going to respond to, whether they’re going to respond to very expensive surgical interventions, injections, blocks, and other things that are done to almost everyone with chronic pain right now irrespective of what the underlying mechanism of their pain is.”
Dr. Woolf said another challenge is finding animal models that really reflect how pain is experienced.
“This is a real concern, one that I think anyone working in pain needs to think about,” he said. “We still remain very poor at studying exactly what an animal is feeling.”
An Astounding Finding
It’s not enough to simply apply a stimulus and gauge a reflex response, he said. It’s the voluntary behavior that really matters.
In a recent study by his laboratory, researchers applied a pain stimulus then observed how that affected mice’s natural inclination to run in wheels that were readily available. The amount of running dropped to 40% compared to controls. Interestingly, by the third day after the stimulus was given, the mice were back to normal running in spite of the continued presence of mechanical allodynia.