Chronic pain is one of the most significant medical and scientific challenges in western society today. As well as the emotional and physical effects on the individual it proves to be a significant financial burden to society. Studies have shown that chronic pain leads to central sensitisation that is partially regulated by release of proinflammatory molecules within the CNS. Most work has concentrated on the role of the spinal cord and little is known about changes in supraspinal regions. The CFA footpad model was used to investigate the expression of inflammatory mediators in the brain in persistent inflammatory pain. Using RT-PCR, gene expression of inflammatory mediators was measured in various brain regions. Consistent with previous reports at 7 and 14 days post-injection IL1β expression was significantly elevated in the posterior of the brain (p<0.05), TNFα showed differential expression with a significant increase in the posterior ipsilateral brain region at 72 hours (p<0.05). The chemokine CXCL1 was significantly elevated at 6 hours post-injection (p<0.05) suggesting a role for this chemokine in regulation of the acute pain response. Contrary to evidence from the spinal cord, CX3CL1 and its receptor CX3CR1 were down regulated in the brain at 6 and 24 hours post-injection. Differential expression of astrocyte activation was identified by GFAP immunochemistry. Hypoxia has been implicated in neurodegeneration, a process thought to play a role in chronic pain. Here Hypoxia inducible factor (Hif1α) mRNA expression within the brain was not altered in a CFA model of peripheral inflammation. Interestingly, using Hypoxyprobe immunohistochemistry, a higher level of hypoxia was identified in non-injected controls than in CFA treated animals. This is the first evidence of differential chemokine expression in the brain in persistent inflammatory pain and the first study to suggest a potential role for differential oxygenation within the brain in this condition.

No description available.

<p>  Fetal Alcohol Syndrome (FAS) is the most serious form of Fetal Alcohol Spectrum Disorders (FASD) and the most prevalent neurodevelopmental disorder in North America. Patients with FAS may exhibit cognitive problems with working memory, manipulating information, and reduced executive functioning. Additionally, previous studies exhibited that stress responses are affected by prenatal alcohol consumption Gut microbiota compositions can also influence stress responses and memory, as several studies have shown strong relationships between the enteric gut system and the brain. However, few studies have examined how prenatal alcohol exposure’s effects on the gut microbiome and neuroinflammatory responses. For this study, pregnant HsdBlu:LE Long Evans rats were treated with either a dry diet, liquid diet, or liquid diet with alcohol. On day 28 and 42 after birth, three male and three female adolescent pups from each treatment group had their gut microbiome (fecal samples) analyzed through 16S rRNA amplicon sequencing. Brain histology staining of the cortex and hippocampus regions was also done to evaluate changes in the CNS through microglial counts and morphology analysis. There were no significant differences in alpha diversity of the fecal microbiome between groups of pups based on prenatal alcohol exposure (PAE), sex, age, the interaction of PAE and sex, or in the morphology of cortex microglia. However, analysis of beta diversity using Bray-Curtis dissimilarity and weighted UniFrac suggested distinct microbial communities between the treatment groups based on PAE and the interaction of PAE, sex, and the interaction between PAE and sex. Microglial count comparisons by PAE or sex were only statistically different in the cortex (p ≤ 0.005). The significance of this study suggests that there are some associations between the gut microbiome and CNS inflammation in rats with PAE. Based on these findings, 11 future studies may implement therapeutics such as antibiotics or probiotics to mitigate cognitive or neural symptoms of FASD affected individuals. </p>