In Bayesian and predictive coding frameworks, the magnitude and precision of pain expectancies are key determinants of perceptual experience However, relatively few studies have directly tested whether this holds for pain, and results so far have been inconclusive. Here, we investigated expectancy effects on pain experiences and affective responses. In two studies, healthy participants (n=30 in each study) received painful electrical stimuli preceded by explicit pain predictions. In study 1, the magnitude of pain predictions and administered pain intensities were varied. In study 2, the magnitude and precision of pain predictions were varied, while administered pain intensity was kept constant. Experienced pain intensity was the primary outcome in both studies. Study 1 found that pain experiences assimilated towards both under- and overpredictions of pain for moderate and very high pain stimuli, but this was not observed for non-painful stimuli. In addition, effects were not necessarily larger with predictions of greater magnitude. Study 2 found assimilation of pain experiences upon under- and overpredictions of pain, regardless of precision level, but no effects on EMG eyeblink startle responses. Moreover, results of both studies showed that under- and overpredictions caused disappointment and relief, respectively. In conclusion, the influence of pain predictions on pain may be more complex than assumed in current theoretical frameworks, with no systematically stronger assimilation of pain experiences to larger and more precise predictions. Since overpredictions are associated with relief, but underpredictions with disappointment, these findings underline the importance of providing realistic predictions when preparing for upcoming painful procedures.

Objective: Uncertainty is unavoidable in medical settings. Finding an optimal way to communicate uncertainty may improve doctor-patient communication and, consequently, patients’ health outcomes. Methods: In our exploratory study, healthy participants (n=30) were repeatedly presented with three highly uncertain pain predictions communicated by a hypothetical doctor. A direct statement of high uncertainty (“I don’t know”) was compared to more indirect predictions (social prediction: “It varies widely among people”; range prediction: “… not painful at all to very highly painful”). These were followed by individually calibrated electrical stimuli of non-, moderately, or very highly painful intensity.Results: The direct expression of uncertainty led to the most intense pain sensation (for moderately painful stimuli only), lowest and most certain pain expectations, lowest trust in the hypothetical doctor, and lowest feeling of being well-informed, especially as compared to the social prediction. No differential effects on anxiety were observed.Conclusions: Expressing high uncertainty indirectly, with reference to the common experiences of others, may be beneficial for optimizing pain experiences and enhancing patients’ trust in a medical professional when dealing with uncertainty. Practice Implications: Our findings inform on how high uncertainty could be best communicated in clinical practice, pointing to advantages of indirect communication.

Hyperproduction of highly active carbonyl compounds and reactive oxygen species initiates the development of oxidative stress in various pathological conditions and protein carbonylation is considered to be one of the key factors in the progression of diabetes mellitus and associated complications. This comparative research aimed to study the effect of metformin and rosuvastatin on the levels of biochemical markers of oxidative stress, glycemic control, and lipid profile in rats with type 2 diabetes mellitus (T2DM) complicated by a brain hemorrhage.T2DM was simulated with a single intraperitoneal injection of nicotinamide and streptozotocin (NA/STZ) to male Wistar rats (n=38). Intracerebral hemorrhage (ICH) was induced by microinjection of 1 μL of bacterial collagenase 0.2 IU/μL into the striatum. Animals were randomized into 5 groups: negative control, intact rats; positive control 1, NA/STZ; positive control 2, NA/STZ+ICH; metformin, 250 mg/kg +NA/STZ+ICH; rosuvastatin, 15 mg/kg+NA/STZ+ICH. Drug effects were assessed by the area under the glycemic curve (AUC), the content of glucose, glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), homocysteine (Hcy), advanced glycation end products (AGEs), and the markers of oxidative modification of proteins – aldehyde- and ketonephenylhydrazones (APH/KPH) in blood serum.It was found that brain hemorrhage in rats with T2DM can intensify the manifestations of oxidative modification of molecules and worsen glycemic control and lipid profile. Under these conditions, rosuvastatin improved lipid metabolism and reduced the levels of AGEs by 35.1% but did not affect glycemia and content of APH/KPH. Metformin reduced oxidative stress (AGEs by 35.4%, KPH by 21.2%) as well as improved both glycemic status and lipid profile (TG level by 20.2%, TG/HDL ratio by 31.9%). Both drugs did not produce any effect on Hcy level.Thus, metformin in conditions of T2DM complicated by acute ICH has advantages over rosuvastatin in relation to the markers of oxidative modification and glycemic control.