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<td><span style="font-family:Helvetica, sans-serif; font-size:20px;font-weight:bold;">NIH Director's Blog Daily Digest (Unofficial)</span></td>
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<td><a href="https://directorsblog.nih.gov/2024/08/29/study-identifies-previously-unknown-pain-control-pathway-underlying-placebo-effect/" style="font-family:Helvetica, sans-serif; letter-spacing:-1px;margin:0;padding:0 0 2px;font-weight: bold;font-size: 19px;line-height: 20px;color:#222;">Study Identifies Previously Unknown Pain Control Pathway Underlying Placebo Effect</a>
<div style="font-family:Helvetica, sans-serif; text-align:left;color:#999;font-size:11px;font-weight:bold;line-height:15px;">Aug 29th 2024, 09:00</div>
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<p><figure class="wp-block-image size-large"><img fetchpriority="high" decoding="async" width="1024" height="576" src="https://directorsblog.nih.gov/wp-content/uploads/2024/08/neuron-circuitboard-3-1024x576.jpg" alt='circuit board with neurons instead of regular circuitry leading to a smiley face icon with the words "pain relief"' class="wp-image-26249" srcset="https://directorsblog.nih.gov/wp-content/uploads/2024/08/neuron-circuitboard-3-1024x576.jpg 1024w, https://directorsblog.nih.gov/wp-content/uploads/2024/08/neuron-circuitboard-3-300x169.jpg 300w, https://directorsblog.nih.gov/wp-content/uploads/2024/08/neuron-circuitboard-3-150x84.jpg 150w, https://directorsblog.nih.gov/wp-content/uploads/2024/08/neuron-circuitboard-3-768x432.jpg 768w, https://directorsblog.nih.gov/wp-content/uploads/2024/08/neuron-circuitboard-3-1536x864.jpg 1536w, https://directorsblog.nih.gov/wp-content/uploads/2024/08/neuron-circuitboard-3-180x100.jpg?crop=1 180w, https://directorsblog.nih.gov/wp-content/uploads/2024/08/neuron-circuitboard-3.jpg 1920w" sizes="(max-width: 1024px) 100vw, 1024px"><figcaption class="wp-element-caption"><em>Credit: Donny Bliss/NIH</em></figcaption></figure>
<p>When someone receives an inactive sugar pill for their pain, the expectation of benefit often leads them to experience some level of pain relief. Researchers have long known that this <a href="https://www.nccih.nih.gov/health/placebo-effect" target="_blank" rel="noreferrer noopener">placebo effect</a> is a very real phenomenon. However, the brain mechanisms underlying the placebo effect for pain have been difficult for researchers to understand.</p>
<p>Now, findings from an intriguing NIH-supported study in mice published in <a href="https://www.nature.com/articles/s41586-024-07816-z" target="_blank" rel="noreferrer noopener"><em>Nature</em></a> offer insight into how this powerful demonstration of the mind-body connection works in the brain. Furthermore, the researchers identified a previously unknown neural pathway for pain control and suggest that specifically activating this pathway in the brain by other means could one day offer a promising alternative for treating pain more safely and effectively than with current methods, including opioids.</p>
<p>The findings come from a team led by <a href="https://www.med.unc.edu/cellbiophysio/directory/gregory-scherrer-phd/" target="_blank" rel="noreferrer noopener">Grégory Scherrer</a>, University of North Carolina School of Medicine, Chapel Hill; with colleagues from Stanford University, Stanford, CA; the Howard Hughes Medical Institute, Ashburn, VA; and the Allen Institute for Brain Science, Seattle. The researchers knew from earlier human brain imaging studies that the placebo effect activates certain brain areas, including the anterior cingulate cortex, which is involved in emotion, attention, and mood. By conducting a series of more detailed studies in mice, the team sought to learn more about the specific brain activities involved.</p>
<p>To do this, the researchers set up an experiment in which mice were put in an apparatus with two distinct chambers, each with comfortably warm floors (about 86 degrees Fahrenheit). After a period of acclimatization, the floor of one of the chambers was made unpleasantly hot (about 118 degrees Fahrenheit—similar to hot pavement in the summertime). The mice learned that they could avoid their discomfort by spending time in the chamber with the comfortably warm floor. The researchers then equalized the floor temperature in both chambers to 118 degrees. Despite identical hot conditions in both chambers, the mice still exhibited fewer behaviors associated with discomfort, such as paw licking, in the chamber that was previously comfortable, indicating that the animals showed signs of a classic placebo effect.</p>
<p>The researchers used a variety of sophisticated imaging techniques to visualize the activity of individual neurons in mice to better understand their behaviors. They found the placebo effect links the anterior cingulate cortex in the front of the brain through the pontine nucleus, a part of the brain with clusters of cells in the brainstem that has not previously been associated with pain or pain relief, to the cerebellum in the back of the brain. This research indicates that the pontine nucleus could be a promising target for novel pain-relieving therapies.</p>
<p>The experiments also revealed an unexpected abundance of opioid receptors in the pontine nucleus, lending further support for the role of this brain area in responding to the body’s natural opioids that modulate pain.</p>
<p>While the experience of pain is exceedingly complex, and this research is in mice, the researchers expect that these findings will have relevance to people. The next step is to explore the role of activity in this newly discovered pain pathway in humans’ experience of the placebo effect. The hope is that with continued study it may one day be possible to target this brain area using small molecules or neural stimulation as a potentially more effective and safer means to ease pain compared to current methods.</p>
<p><strong>Reference:</strong></p>
<p>Chen C, <em>et al</em>. <a href="https://pubmed.ncbi.nlm.nih.gov/39048016/" target="_blank" rel="noreferrer noopener">Neural circuit basis of placebo pain relief</a>. <em>Nature</em>. DOI: 10.1038/s41586-024-07816-z (2024).</p>
<p><em>NIH Support: National Institute of Neurological Disorders and Stroke, National Institute on Drug Abuse</em></p></p>
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<p><strong>Forwarded by:<br />
Michael Reeder LCPC<br />
Baltimore, MD</strong></p>
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