Earlier this year, scientists, politicians and other healthcare advocates came together to share their hopes for the next decade of neuroscience research at the One Mind for Research (OMR) Summit in Boston. At a session highlighting the neurobiological consequences of war, Clifford J. Woolf, a pain researcher at Harvard Medical School and Children’s Hospital Boston, stated, “We have made enormous progress in promoting survival…but, in fact, an area that has really lagged behind relates to the pain associated with combat injury.”
The word that many locked on to in that statement was lagged. In a variety of publications and meetings in the past few years, the idea that the study and treatment of pain, particularly chronic or neuropathic pain, is somehow behind where it should be keeps coming to the surface—and that is whether it's pain associated with combat, cancer, or some other disease state. But with more than a dozen research journals dedicated solely to the topic of pain and thousands of new pain-related papers being published each year, does a word like lagged accurately reflect the state of its study?
Is it lagging?
When I asked Woolf that question a few weeks after the OMR meeting, he clarified his statement. “There have been a lot of people studying pain for some time. Still, it’s not clear exactly why there is a differential susceptibility in different individuals to develop persistent neuropathic pain,” he said. “And that’s something we now have the tools to find out.”
But Irene Tracey, a neuroscientist who studies pain at the University of Oxford, believes that the study of pain has, indeed, lagged, in comparison with ailments like cancer and heart disease—mainly because it doesn’t fit into one unique condition. “Historically, pain was perceived as a symptom. And it was a symptom present in many different conditions. When treated, it was as part of one of those conditions,” she says. “But there’s been a bit of a paradigm shift. What we now realize is that when pain goes chronic, it is a separate entity and something that can be seen in the brain.” Recent studies have shown that chronic pain, over time, results in the widespread loss of gray matter in areas including the cingulate and orbitofrontal cortex.
The challenges of studying pain
People who visit their healthcare provider with pain issues, whether they are hurting due to arthritis or a traumatic brain injury, are asked to rate their experience using numbered pain scale. Unfortunately, when the number on that scale doesn’t sync up with an observable injury, frustrated patients are usually sent home with little relief (and, too often, disbelief from their physicians). One of the biggest challenges of studying pain from the neurobiological perspective is that it is a complex and multifactorial experience—and one that is hard to operationally define.
“Pain is not a unitary thing. It is a perception of hurt that is experienced,” says Tracey. “It’s a bit like trying to ask, ‘What is joy? What is pleasure?’ It’s difficult to define and it doesn’t help that the experience is highly malleable.”
While that sensation of hurting is common to pain as a symptom, Tracey’s neuroimaging studies have demonstrated that one’s perception of pain can be changed quite dramatically even when the stimulus is the same. “In one of our acute pain experiments, I give the same thermal temperature as a stimulus,” she says. “But the experience of pain participants report varies enormously depending on the context, their anxiety, their depression, or their attention to the pain itself. Pain is not a unitary thing—and, as you would expect, it’s not done by just one bit of the brain.”
A second challenge to the study of pain has been translating the experience to animal models—and then back again. Rajesh Khanna, a researcher at Indiana University who studies pain at the molecular level, has discovered a promising target, a neuropeptide called CBD3, for future pain treatments. But, despite this success, he admits pain is a very human phenomenon. “Pain is something that is really hard to model in a cell dish, or a culture or even in an animal,” he says. “But you have to start somewhere.”
The search for a treatment
The ultimate goal for most modern pain research is new pharmacological treatments—pills that will help those suffering from chronic pain manage the experience with more ease. Yet, to date, while there are several interesting molecular targets, including Khanna’s, there has been no “smoking gun” type result that can promise an end to pain. Ken Casey, a veteran pain researcher at the University of Michigan, hopes focusing on the brain’s natural built-in mechanisms to control pain will be a fruitful line of study.
Woolf, however, is lobbying for more in-depth genetic studies concerning pain. “What has become clear from the study of identical and non-identical twins is that 50 percent of the variance in pain sensitivity is heritable. There is a big genetic component that we still need to understand,” he says. “We need to identify those genes and then, hopefully, use those genes to diagnose who may be at risk for chronic pain—and maybe develop new forms of analgesia based on them.”
Casey believes all these avenues of research, from genetics to molecular biology to neuroimaging, are helpful to better understand the sources and development of chronic pain. But he does advise caution.
“Frankly, I don’t know that we could ever stop pain altogether. I don’t know what we’d want to—it’s there for a reason,” he says. “Ultimately, I believe we’ll come to the realization that trying to completely eliminate pain will have results that are less desirable than the pain itself. But that’s something we still need to find out.”