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From Cue to Meaning



The 2024 Global Year will examine what is known about sex and gender differences in pain perception and modulation and address sex-and gender-related disparities in both the research and treatment of pain.

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Sensory cues in our environment continuously guide processing in the brain. A simple touch, tone or a flash of light shapes our thought process countless numbers of times per day. In pain, cues leading to expectations of higher upcoming pain not only increase subjective pain ratings, but also increase the degree of activity in brain areas engaged in pain processing. In a similar fashion, expectations of lower pain decrease pain-related brain activations and subsequent pain scores. Finally, placebo cues consistently decrease pain in both acute and chronic pain states. In the pain world, just like in life in general, expectations of the outcome have a strong influence on what that outcome is going to be. As Henry Ford said (not about pain, of course), “Whether you think you can, or you think you can’t – you’re right.”

The mechanisms by which sensory cues that provide information about upcoming pain get transformed into expectations that then shape the processing of experienced pain are still largely unknown. We know that signals from the eyes will travel to the occipital cortex in the back of the brain, where visual information is processed. We know that signals from touch will go from receptors in the skin to the thalamus and to the somatosensory cortices. But if both visual and somatosensory cues mean the same thing, (ie, either high or low pain in several seconds), do they end up activating the same brain regions? Would these brain regions be positioned to shape how pain is then processed and perceived?

To answer these questions, we guided our subjects’ expectations regarding upcoming pain (low or high) via either visual or thermal nonpainful cues. We then scanned their brain with MRI to see what happens in the time period between getting a cue and experiencing low or high pain.

As expected, visual information initially went to visual cortex and somatosensory information initially went to the somatosensory cortex. However, very quickly, it no longer mattered whether information arrived from a visual or a somatosensory cue. What mattered was the meaning. When a cue signaled high upcoming pain, it activated the anterior cingulate and prefrontal cortices, regardless of the type of sensory cue. When the cue signaled low upcoming pain, it activated the posterior parietal cortex, regardless of the type of sensory cue.

Interestingly, both the anterior cingulate and prefrontal cortices are crucial mediators between an expectation and an experience. In previous work, these areas exhibited graded activation depending on the magnitude of expected pain. In other words, they were activated more when subjects expected more pain. Furthermore, when the prefrontal cortex is temporarily “turned off” with transcranial magnetic stimulation, subjects can no longer experience the effect of placebo. Similarly, patients with Alzheimer’s, whose prefrontal cortex is severely affected by the disease, also have diminished placebo effect.

Together, cues arising from different sensory modalities ultimately engage common brain mechanisms that reflect the meaning of the cue. This meaning-related activity is presumably critical for preparing sensory systems to optimally process afferent information.

 About Oleg Lobanov

Oleg Lobanov

Dr. Oleg V. Lobanov did his PhD work in the Laboratory of Pain and Cognition under the guidance and supervision of Dr. Robert C. Coghill. Oleg is in his final year of MD/PhD program at Wake Forest School of Medicine, and is applying for residency programs in Child Neurology.

Oleg’s research interests include higher cognitive brain functions (attention, expectation) in pain, their brain mechanisms and their influence on experience of pain. He hopes to find another angle in chronic pain treatment through manipulations of attention and expectation.


Lobanov OV, Zeidan F, McHaffie JG, Kraft RA, & Coghill RC (2014). From cue to meaning: brain mechanisms supporting the construction of expectations of pain. Pain, 155 (1), 129-36 PMID: 24055334

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