Allopregnanolone Levels Are Inversely Associated with Self-Reported Pain Symptoms in U.S. Iraq and Afghanistan-Era Veterans: Implications for Biomarkers and Therapeutics.

BACKGROUND AND OBJECTIVES: Pain symptoms are common among Iraq/Afghanistan-era veterans, many of whom continue to experience persistent pain symptoms despite multiple pharmacological interventions. Preclinical data suggest that neurosteroids such as allopregnanolone demonstrate pronounced analgesic properties, and thus represent logical biomarker candidates and therapeutic targets for pain. Allopregnanolone is also a positive GABAA receptor modulator with anxiolytic, anticonvulsant, and neuroprotective actions in rodent models. We previously reported inverse associations between serum allopregnanolone levels and self-reported pain symptom severity in a pilot study of 82 male veterans. METHODS: The current study investigates allopregnanolone levels in a larger cohort of 485 male Iraq/Afghanistan-era veterans to attempt to replicate these initial findings. Pain symptoms were assessed by items from the Symptom Checklist-90-R (SCL-90-R) querying headache, chest pain, muscle soreness, and low back pain over the past 7 days. Allopregnanolone levels were quantified by gas chromatography/mass spectrometry. RESULTS: Associations between pain ratings and allopregnanolone levels were examined with Poisson regression analyses, controlling for age and smoking. Bivariate nonparametric Mann–Whitney analyses examining allopregnanolone levels across high and low levels of pain were also conducted. Allopregnanolone levels were inversely associated with muscle soreness [P = 0.0028], chest pain [P = 0.032], and aggregate total pain (sum of all four pain items) [P = 0.0001]. In the bivariate analyses, allopregnanolone levels were lower in the group reporting high levels of muscle soreness [P = 0.001]. CONCLUSIONS: These findings are generally consistent with our prior pilot study and suggest that allopregnanolone may function as an endogenous analgesic. Thus, exogenous supplementation with allopregnanolone could have therapeutic potential. The characterization of neurosteroid profiles may also have biomarker utility.

Redeeming Faustus: Tracing the pacts of Mariken and Faust from the 1500s to the present

This dissertation uncovers and analyzes the complicated history of the devil’s pact in literature from approximately 1330 to 2015, focusing primarily on texts written in German and Dutch. That the tale of the pact with the devil (the so-called Faustian bargain) is one of the most durable and pliable literary themes is undeniable. Yet for too long, the success of Johann Wolfgang von Goethe’s Faust I (1808) decisively shaped scholarship on early devil’s pact tales, leading to a misreading of the texts with Goethe’s concerns being projected onto the earliest manifestations. But Goethe’s Faust really only borrows from the original Faust his name; the two characters could not be more different. Furthermore, Faustus was not the only early pact-maker character and his tale was neither limited to the German language nor to the Protestant faith. Among others, tales written in Dutch about a female, Catholic, latemedieval pact-maker, Mariken van Nieumeghen (1515), illustrate this. This dissertation seeks to redeem the early modern Faustus texts from its misreading and to broaden the scholarship on the literature of the devil’s pact by considering the Mariken and Faust traditions together.

The first chapter outlines the beginnings of pact literature as a Catholic phenomenon, considering the tales of Theophilus and Pope Joan alongside Mariken of Nijmegen. The second chapter turns to the original Faust tale, the Historia von D. Johann Fausten (1587), best read as a Lutheran response to the Catholic pact literature in the wake of the Reformation. In the third chapter, this dissertation offers a new, united reading of the early modern Faust tradition. The fourth and fifth chapters trace the literary preoccupation with the pacts of both Mariken and Faustus from the late early modern to the present.

The dissertation traces the evolution of these two bodies of literature and provides an in-depth analysis and comparison of the two that has not been done before. It argues for a more global literary scholarship that considers texts across multiple languages and one that takes into consideration the rich body of material of the pact tradition.