Peripheral Inflammation is accompanied by Cerebral Hypoperfusion in Mice

Chronic pain is a disabling condition that is accompanied by neuropsychiatric comorbidities such as anxiety, depression, and cognitive decline. While the peripheral alterations are well-studied, we lack an understanding of how these peripheral changes can result in long-lasting brain alterations and the ensuing behavioral phenotypes. This study aims to quantify changes in cerebral blood perfusion using laser speckle contrast imaging (LSCI) in the murine Complete Freund's adjuvant (CFA) model of unilateral peripheral inflammation.

Twenty female and 24 male adult C57BL/6 mice were randomly assigned to control (0.05ml saline) or 1 of 3 experimental groups receiving CFA (0.01ml, 0.05ml, and 0.1ml) on the right hindpaw. Three days after the intraplantar injections, animals were assessed for signs of pain (von Frey), working memory (y-maze), and anxiety (zero maze and open field), and subjected to craniotomy and in vivo LSCI of the parietal-temporal lobes.

Unilateral administration of CFA resulted in signs of local inflammation, decreased mechanical thresholds on the affected hindpaw, signs of anxiety in the zero maze, as well as cerebral hypoperfusion in dose-dependent manner.

To our knowledge, this is the first study using laser speckle contrast imaging to examine the effects of CFA-induced peripheral inflammation on cerebral blood perfusion. It serves as a first step in delineating the path by which insult to peripheral tissues can cause long-lasting brain plasticity via vascular mechanisms.