Research has shown that people consistently rate pain occurring around the head as more debilitating and emotionally draining compared to pain from elsewhere in the body.Scientists from Duke University have revealed why this pain can be more disruptive than any other: The answer may lie not only in whatever is reported to us by the five senses but also in the emotional feelings created by that sensation.

In a report published online on November 13 in Nature Neuroscience, the researchers explain that this pain is more defined because sensory neurons from the head and face are connected directly to one of our brain's primary emotional signaling focal points.While sensory neurons from other parts of the body are also wired to this central hub, their link is indirect.The team believes this study may pave the way for more efficient solutions for chronic head pain.

"In typical cases, health practitioners focus on treating the sensation of pain only, but these results show that we need to address the emotional aspects of pain as well," said Fan Wang, Duke University's professor of neurobiology and cell biology, and senior author of the study.

Since pain signals from the head and face versus those from the body are transmitted to the brain via two separate groups of sensory neurons, it is possible that neurons from the head are just more sensitive to pain than those from the rest of the body.However, the difference in sensitivity is not enough to explain the greater fear and emotional suffering that a person undergoes in response to head pain compared to body pain, Wang argued.

In the study, the scientists used personal accounts of patients suffering from prominent fear and emotional pain, as well as functional Magnetic Resonance Imaging (fMRI), which showed that there was more activity in the amygdala region of the brain in response to head pain than in response to pain from elsewhere on the body.Amygdala is the part of the brain that is involved in emotional experiences.

Wang pointed out that although human studies have revealed that pain in the head and face seem to trigger the emotional system more extensively, the underlying mechanisms are still unclear.

To analyze the neural circulatory system behind the two kinds of pain, Wang and her colleagues studied brain activity in mice.When they irritated either the rodent's paw or face, they noticed that introducing strain to the face led to significantly higher activity in the parabrachial nucleus (PBL), a region in the brain that is directly connected to the instinctive and emotional areas, compared to that on the paw.

Next, they introduced methods based on a new technology that was recently developed by Wang's team, called CANE (capturing activated neuronal ensembles).The novel technique enabled them to identify the sources of neurons in the brain that result in this elevated PBL activity.

"It was a eureka moment," Wang said, "because neurons from the body only have this indirect connection to the PBL, whereas those from the head and face, besides this indirect input, also have a direct pathway." This difference explains why there is stronger activation in the amygdala and the emotional centers of the brain as a result of pain from the head and face.

Upon further investigation, Wang and her team found that activating this pathway evoked face pain, while silencing the path caused it to subside.

"So far we have the basic biological explanation for why this kind of pain is so much more emotionally derailing than others," said the paper's co-author Wolfgang Liedtke, a professor of neurology at Duke University Medical center.Liedtke also works with patients suffering from the head- and face-pain.He went on to point out that their work will open the door towards a more profound understanding of chronic head and face pain, as well as toward translating this discovery into therapies that will benefit patients.

Many forms of chronic head-face pain such as trigeminal neuralgia and cluster headaches can become so severe that patients resort to surgical solutions like severing the particular neural pathways that transmit pain signals from the head and face to the hindbrain.A substantial number of patients, however, continue to experience pain even after undergoing these invasive procedures.

Qiufu Ma, a professor of neurobiology at Harvard Medical School, who was not part of the study, also believes the research will go a long way in helping doctors deal with chronic pain. "Among the most debilitating types of pain are those that occur in the head regions, such as a migraine." He said. "With this discovery of the direct pain pathway, we might finally have an explanation for why facial pain is much more severe and more unpleasant."

In the future, targeting the neural pathway identified by Wang and her team from Duke could be the best approach toward developing innovative therapies for dealing with head and face pain.