Friday, December 29, 2017

Mouse Study: Head Pain Taps into Brain’s Emotional Hub

Mouse Study: Head Pain Taps into Brain's Emotional Hub

Pain experienced in the head and face, including the eyeballs, ears and teeth is consistently rated by patients as causing more suffering and being more emotionally draining compared to pain in other parts of the body.

In fact, the suffering caused by chronic head-face pain, such as cluster headaches and trigeminal neuralgia, can become so severe that patients seek surgical procedures, even severing the known neural pathways that carry pain signals from the head and face to the hindbrain. But a substantial number of patients continue to suffer, even after these extreme measures.

In a new mouse study, Duke University scientists have discovered how the brain’s wiring may be behind the severe suffering involved in head and face pain. The reason goes beyond the five senses and into how the pain sensations make us feel emotionally.

Specifically, sensory neurons that serve the head and face are wired directly into one of the brain’s primary emotional signaling hubs. Sensory neurons found in other parts of the body are also connected to this hub, but only indirectly.

“Usually doctors focus on treating the sensation of pain, but this shows the we really need to treat the emotional aspects of pain as well,” said Dr. Fan Wang, a professor of neurobiology and cell biology at Duke, and senior author of the study.

Pain signals from the head are carried to the brain through two different groups of sensory neurons, and it is possible that these head neurons are simply more sensitive to pain than those from the body. But differences in sensitivity alone cannot explain the greater fear and emotional suffering that patients experience in response to head-face pain than body pain, Wang said.

Patient reports of greater fear and suffering from head and face pain are backed up by functional magnetic resonance imaging (fMRI), which shows greater activity in the amygdala — a region of the brain involved in emotional experiences — in response to head pain than in response to body pain.

“There has been this observation in human studies that pain in the head and face seems to activate the emotional system more extensively,” Wang said. “But the underlying mechanisms remained unclear.”

To investigate the neural circuitry underlying the two types of pain, the researchers tracked brain activity in mice after irritating either a paw or the face. The results show that irritating the face led to greater activity in the brain’s parabrachial nucleus (PBL), a region that is directly wired into the brain’s instinctive and emotional centers.

Then they used methods based on a novel technology recently pioneered by Wang’s group, called CANE, to identify the sources of neurons that led to this elevated PBL activity.

“It was a eureka moment because the body neurons only have this indirect pathway to the PBL, whereas the head and face neurons, in addition to this indirect pathway, also have a direct input,” Wang said. “This could explain why you have stronger activation in the amygdala and the brain’s emotional centers from head and face pain.”

Further experiments showed that activating this pathway prompted face pain, while silencing the pathway reduced it.

“We have the first biological explanation for why this type of pain can be so much more emotionally taxing than others,” said Dr. Wolfgang Liedtke, a professor of neurology at Duke University Medical Center and a co-author on Wang’s paper, who is also treating patients with head- and face-pain.

“This will open the door toward not only a more profound understanding of chronic head and face pain, but also toward translating this insight into treatments that will benefit people.”

Liedtke said targeting the neural pathway identified here can be a new approach toward developing innovative treatments for this devastating head and face pain.

The study is published in the journal Nature Neuroscience.

Source: Duke University



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