Placebo and nocebo effects are positive and negative treatment-like effects, respectively, that cannot be attributed to an active treatment component. They are caused by patients’ expectations of...Show morePlacebo and nocebo effects are positive and negative treatment-like effects, respectively, that cannot be attributed to an active treatment component. They are caused by patients’ expectations of symptom improvement or worsening. Both effects play a significant role in the treatment of itch. However, there is a great variability in their extent in healthy individuals and patient groups, which may be partly explained by genetic variants in specific neurotransmitter pathways. This study is the first to investigate genetic predictors of placebo and nocebo effects on itch. Based on research in pain, the genes COMT rs4680, FAAH rs324420, and OPRM1 rs1799971 were identified to investigate their potential role in the extent to which placebo and nocebo effects on itch were induced in healthy individuals. This cross-trial analysis included 58 in the placebo and 127 healthy genotyped participants in the nocebo analysis from three studies. Itch stimuli were elicited electrically or with histamine, and placebo and nocebo effects were induced with specific learning processes, i.e., conditioning with verbal suggestion, or antihistamine was classically conditioned. COMT met/met variants demonstrated significantly higher placebo effects on itch compared to val/val variants, 95% BCa CI [0.026, 1.263]. No other significant differences were found between the variants of COMT, FAAH and OPRM1 and placebo or nocebo effects on itch. Knowledge on genetic predictors of placebo and nocebo effects on itch could help to improve clinical trial design and allow clinicians to tailor itch-reducing treatments such that they optimize treatment efficacy. Future research should focus on a replication study with a larger cohort and homogenous itch-inducing methods as well as learning processes to verify the studied relationship.Show less
Acute pain has the essential function of protecting organisms from harmful influences through painful signals that trigger protective behavioral responses. Chronic pain, however, has merely stress...Show moreAcute pain has the essential function of protecting organisms from harmful influences through painful signals that trigger protective behavioral responses. Chronic pain, however, has merely stress-inducing and disabling characteristics. To enable the development of treatment, understanding the mechanisms underlying pain experience is indispensable. Previous research has demonstrated how expectancy-induced nocebo effects (i.e., the worsening of a symptom caused by negative expectations) can provoke hyperalgesia, an increased sensitivity towards pain. The present study aimed to reproduce these findings and investigate the precise role of expectancies in the relationship between nocebo-inducing cues and the resulting pain experience. Within the context of expectancy, this study was further exploring the degree of awareness involved in the participants’ perception of their accuracy in predicting upcoming pain intensities. Sixty-nine healthy volunteers were divided between the experimental and the control condition, both of which received repeated electrical pain stimulation. Through verbal suggestion and conditioning, the experimental group learned to associate a specific color with high pain intensity and a second color with a medium intensity stimulus. In the control group, there were no instructions and the order of pain intensities and color cues was randomized. During the test phase, all color cues were accompanied by medium intensity pain to measure the magnitude of nocebo responses associated with the conditioned color as opposed to the control color. Pain expectancy and experience, as well as the extent to which they both matched, were measured through self-report scales after each stimulus-color pair. Nocebo conditioning produced the expected higher pain and expectancy ratings for the conditioned cue, as compared to the unconditioned cue in the nocebo group’s test data. Next, expectancies appeared to significantly mediate the effect of the nocebo-induction on pain experience in the experimental group. Finally, there was no significant indication that participants were aware of their degree of prediction accuracy. These findings confirm the significant involvement of expectation in pain experience and warrant further research on awareness in pain perception. Additional research is needed to provide deeper insight on the psychological processes underlying pain experience, as it will help optimize treatments for patients suffering from chronic pain.Show less
Background: People with type 1 diabetes (T1D) often experience problems with their glucose regulation (glucose variability and glucose control), sleep quality, and cognitive functioning. However,...Show moreBackground: People with type 1 diabetes (T1D) often experience problems with their glucose regulation (glucose variability and glucose control), sleep quality, and cognitive functioning. However, their interrelation has not often been investigated. The aim of this study was to investigate how sleep quality and cognitive functioning are associated with glucose regulation in people with T1D. Method: Continuous glucose monitoring (CGM) data was collected over two weeks, in 18 participants, while each day subjective sleep quality (once in the morning) and cognitive functioning (e.g., ability to concentrate, finding words) (up to five times during the day) was measured using ecological momentary assessments (EMAs). Based on the CGM data, glycemic parameters (glucose variability and glucose control) during the night and day were calculated and a mean value of cognitive functioning per day was composed. Linear mixed model analyses were used to test for 1) whether sleep quality was influenced by glycemic parameters during the night and 2) whether cognitive functioning during the day was influenced by sleep quality and whether cognitive functioning was associated with glycemic parameters during the day. In addition, an interaction effect between sleep quality and glucose variability on cognitive functioning was explored. Lastly, visual plots were used to explore the associations on an individual level. Results: No statistically significant main effects were found for either association. However, an interaction trend (ß = -2.07, p = .070) between sleep quality and glucose variability on cognitive functioning scores was found. For days with normal fluctuations in glucose levels, better sleep quality was associated with better cognitive functioning, whereas for days with high glucose variability, this association could not be found. Regarding the individual plots, both, positive and negative relationships between all mentioned variables were apparent, exemplifying important inter-individual differences. Conclusion: For people with T1D, the relationships between glucose parameters, sleep quality, and cognitive functioning, vary from person to person. This finding advocates for looking at the individual level when implementing possible treatment methods for increasing sleep quality and cognitive functioning. More research in a larger sample is warranted to further examine the inter-individual factors in these associations.Show less
