We need to understand the importance of the brain and patient's pain and try to take steps to figure out in an individual patient to what degree is the brain driving their pain and to what degree is the body driving their pain. Because in some sense, the treatments we use to target the brain are different from the treatments we would use to target the body, and we need to match our treatments to the mechanisms that are driving pain in an individual patient. I think there is evidence that at least in certain individuals and potentially for certain pain conditions, chronic pain is largely a brain disease. On the structural side, there is evidence that areas of the brain atrophy in people with chronic pain and some of those reductions and brain volume can be corrected or normalized by successfully treating the pain. So it looks like the experience of chronic pain itself is for some reason associated with structural changes in the brain and if we can successfully reduce the pain or remove the pain, we can help that brain get back to normal. But there are also many, many studies showing that the brain of certain individuals with chronic pain seems to respond differently than people without chronic pain. We don't know all the details of why it responds differently but it suggests that for at least some patients, for our treatments to be effective, they're going to have to target and impact the functioning of the brain.
The prototypical centralized pain condition is probably fibromyalgia, but this centralized pain can be a component of almost any chronic pain condition. Studies have shown that people who have knee arthritis and high levels of clinical pain tend to show whole body increases in pain sensitivity. There's some evidence that their brains have been changed as a result of their arthritis and their ongoing chronic pain. I'm not suggesting that the brain is the only thing that's important here but if we're going to be successful, our treatments need to target both the brain and the body in order to reverse some of the changes in brain structure and function that have emerged. Other pain conditions that are often thought of as having an important central component include temporomandibular disorders, irritable bowel syndrome, some headache disorders and interestingly, many of these pain conditions co-occur. That suggest to us that some of the mechanisms underlying these different pain conditions overlap and create co-occurrence or comorbidity in the pains within the same person. Looking to the future, one of the big questions to explore is what is changing this brain structure and function? Can we identify neurochemical targets that we might be able to address with either existing or new medications? Another area in which there is a lot of interest is can we modulate the functioning of the brain non-invasively? There are certain brain stimulation techniques from magnetic stimulation to electrical stimulation that may have clinical benefit.