Glucocorticoid Hormones as Modulators of the Kynurenine Pathway in Chronic Pain Conditions.

The pathogenesis of chronic pain entails a series of complex interactions among the nervous, immune, and endocrine systems. Defined as pain lasting or recurring for more than 3 months, chronic pain is becoming increasingly more prevalent among the US adult population. Pro-inflammatory cytokines from persistent low-grade inflammation not only contribute to the development of chronic pain conditions, but also regulate various aspects of the tryptophan metabolism, especially that of the kynurenine pathway (KP). An elevated level of pro-inflammatory cytokines exerts similar regulatory effects on the hypothalamic-pituitary-adrenal (HPA) axis, an intricate system of neuro-endocrine-immune pathways and a major mechanism of the stress response. As the HPA axis counters inflammation through the secretion of endogenous cortisol, we review the role of cortisol along with that of exogenous glucocorticoids in patients with chronic pain conditions. Considering that different metabolites produced along the KP exhibit neuroprotective, neurotoxic, and pronociceptive properties, we also summarize evidence rendering them as reliable biomarkers in this patient population. While more in vivo studies are needed, we conclude that the interaction between glucocorticoid hormones and the KP poses an attractive venue of diagnostic and therapeutic potential in patients with chronic pain.

Starvation as cause of death in the Croatian Quarnero and hinterland between 1816 and 1825.

Our aim is to investigate starvation as cause of death and social and demographic consequences in the Croatian Quarnero and its hinterland between 1816 and 1825, paying particular attention to the infamous "year of famine" 1817. Our sources were: registers of births, marriages, and deaths from 21 parishes kept at the Croatian State Archives in Rijeka and Zagreb. We collected and processed data for statistical analysis according to the date of baptism (birth), marriage, and death, and according to sex and age. Our focus was on recorded causes of death. Between 1816 and 1825, 15,701 children were baptised (born), and 11,021 people died. Starvation was recorded as cause of death in 255 cases, of which 198 were recorded in the infamous 1817. It was the only year with negative growth in virtually all parishes, with the birth-to-death ratio of 1147:1545. In 1817, the proportion of death by starvation to the total death rate was 12.8% for the entire area, with the highest share recorded in Veprinac (33.3%), Crikvenica (23.3%), and Kastav (15.8%). Death by starvation was more common in men than in women (56.7% vs. 43.3%, respectively). Age distribution was as follows; in the population below 20 years of age the death rate was 42 (16.5% of total deaths), but the most affected age group were infants and children aged 1-4 years (69.0%) whereas in adult population the death rate was 213 (83.5% of total deaths) and the most affected group were the elderly between 60 and 69 years (26.3%). Analysis shows lower birth and marriage rates between 1816 and 1818, followed by a steep rise and a plateau with minimal variation. This study shows that the Croatian Quarnero and its hinterland suffered a great famine in the early 19th century and 1817 in particular, which had left a deep mark on local demography, just like in the neighbouring parts of Croatia and Europe.