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Opioidergic activation of the descending pain inhibitory system underlies placebo analgesia.

Sci Adv

January 2025

Laboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.

Placebo analgesia is caused by inactive treatment, implicating endogenous brain function involvement. However, the neurobiological basis remains unclear. In this study, we found that μ-opioid signals in the medial prefrontal cortex (mPFC) activate the descending pain inhibitory system to initiate placebo analgesia in neuropathic pain rats.

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Although the pathophysiology of pain has been investigated tremendously, there are still many open questions with regard to specific pain entities and their pain-related symptoms. To increase the translational impact of (preclinical) animal neuroimaging pain studies, the use of disease-specific pain models, as well as relevant stimulus modalities, are critical. We developed a comprehensive framework for brain network analysis combining functional magnetic resonance imaging (MRI) with graph-theory (GT) and data classification by linear discriminant analysis.

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The brain is composed of a dense and ramified vascular network of arteries, veins and capillaries of various sizes. One way to assess the risk of cerebrovascular pathologies is to use computational models to predict the physiological effects of reduced blood supply and correlate these responses with observations of brain damage. Therefore, it is crucial to establish a detailed 3D organization of the brain vasculature, which could be used to develop more accurate in silico models.

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A fundamental issue in neuroscience is a lack of understanding regarding the relationship between brain function and the white matter architecture that supports it. Individuals with chronic neuropathic pain (NP) exhibit functional abnormalities throughout brain networks collectively termed the "dynamic pain connectome" (DPC), including the default mode network (DMN), salience network, and ascending nociceptive and descending pain modulation systems. These functional abnormalities are often observed in a sex-dependent fashion.

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