The influence of treatment-history on the perceived efficacy of analgesic treatments

• Applicant: Alexandra Tinnermann, Ph.D.
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 446809326

The aim of this research project is to investigate how previous analgesic treatment experiences influence placebo-related expectations about current analgesic treatments and how these expectations modulate central pain processing. Particularly, the proposed study will examine if the order of different levels of efficacy in an analgesic treatment (treatment-history) influences expectations about treatment efficacy and thus modulates the perceived analgesic effect in two groups of participants. During the treatment-history phase, one group will start with a weak treatment whose efficacy will increase over time while the other group will start with a strong treatment whose efficacy will decrease over time. During the test phase, both groups will receive a medium effective treatment to test if these two treatment-histories modulate the perceived analgesic efficacy. This study design will allow testing whether a dosing scheme that initially includes the experience of a strong treatment is more effective in generating high expectations to boost treatment efficacy than the dosing scheme proposed by WHO and other pain societies that includes the incremental increase of doses in analgesic treatments. Since placebo-related expectations have been shown to contribute to the efficacy of analgesic treatments beyond their pharmacological effect, the benefit of identifying a dosing scheme that maximizes placebo-related expectations might decrease the overall quantity of analgesic drug intake in pain management. The proposed study will further apply simultaneous cortico-spinal fMRI to investigate top-down processes within the central pain system from prefrontal cortex to the spinal cord with regard to treatment-history effects. Importantly, cortico-spinal interactions (functional connectivity) will be investigated within the descending pain system from the prefrontal cortex to brainstem and spinal cord to characterize how experience-generated expectations modulate these interactions. Due to the existing infrastructure for cortico-spinal imaging at the Institute of Systems Neuroscience, this part of the project will be realized in Hamburg. Additionally, this project will implement a Bayesian modeling approach to predict pain relief ratings on the participant level. The aim of the modeling is to clarify whether the first treatment experience within the treatment-history phase mainly contributes to placebo-related expectations during the test phase. This part will be realized in a lab within the Brain and Spine Institute in Paris that has a lot of expertise in Bayesian modeling.

• DFG Programme: WBP Position