The moment we find a useful biomarker, our ability to manage a condition improves: we treat diabetes by following the glycemic index, we treat HIV by following a viral load and a CD4 count. Conditions without biomarkers often frustrate treatment – after all, like the business adage – “you can’t manage what you don’t measure.” Although some diseases fall into this category, frustratingly, so does the symptom of pain. This week’s NEJM reports on a biomarker – specifically a neurologic signature through the use of functional MRI – with the hope that a method to objectively measure pain will allow for titration of medications to achieve effective symptomatic relief in the distressed patient.
There’s no doubt that pain is a serious problem in medicine. At the end of 2010, the IMS Institute for Healthcare Informatics reported on the top 10 most prescribed drugs in the United States, and the chart-topper was the painkiller Vicodin, with a record 131.2 million prescriptions. In hospitals, the most frequently ordered medication is Tylenol; morphine is not far behind. Yet our ability to objectively measure pain, for the past several decades, has been surprisingly basic. Most assessment tools have relied on patient descriptions of their own symptoms. For instance, the McGill Pain Questionnaire of 1975 offered more than fifty words to help a patient describe his pain, including “flickering,” “jumping,” “rasping,” “grueling,” and “drawing.” However, such detailed surveys have been largely abandoned for even more rudimentary measures (“how much pain are you in from a one to a ten?” or “can you point to the face that shows what you are feeling like?”)
Can’t we do any better than this? Maybe. Since the seat of pain perception is in the brain, one idea has been to look at activation of various centers in the central nervous system to track whether activity correlates with the experience of pain. But here’s what complicates things: feeling pain is not just about how hard you are pricked by a pin. Lots of other neural networks modulate the way a painful stimulus feels – the emotional state of the subject, for example, or prior traumatic memories of pain. (Depressed patients are known to have lower thresholds for describing a stimulus as painful). So – the additional challenge in looking at brain activity as a biomarker means sorting out sensory pain from these layers our brain interlaces with the neural processing of pain.
Given such challenges, the investigators from this week’s report use functional MRI to look for a useful neurologic signature, or biomarker. In their study, while participants were being scanned in a functional MRI, investigators applied varying levels of thermal heat to the subject’s forearms, an example of painful heat. Subjects were also exposed to other kinds of pain – including recalling a painful incident (memory of pain) or looking at an image of an ex-lover (social pain). They found that certain areas were specifically stimulated in response to painful heat, including the anterior cingulate cortex and parts of the thalamus. They also found that given an analgesic agent reduced responses in these areas.
So were they successful in finding a biomarker? The results from this study show that the pattern they detected on functional MRI was highly sensitive and specific for painful heat, and this pattern could be used to distinguish thermal pain from the other kinds of pain (the memory of pain, pain anticipation, and pain recall). Such results are proof of a principle – a biomarker for pain probably does exist in the brain, and functional MRI may be one way to get at it. However, questions remain – can such a signature be used to detect non-thermal pain (such as being pricked by a pin?) Might we see such a signature in chronic pain (like in fibromyalgia)?
Possibly – but perhaps it is a fool’s errand to ever expect we will be able to boil down pain, like any other meaningful human experience, to a single number. “From a 1 to a 10,” I ask a patient several times, “how much pain are you in?” He grimaces and finally responds. “I don’t know,” he says, while I push on his stomach. “It’s really hard to explain.”
In the same issue of NEJM, you’ll also find the editorial, “Pain, Heat, and Emotion with Functional MRI.”