Role of the endocannabinoid system in human pain sensitivity, pain plasticity, pain habituation, and neurogenic and non-neurogenic inflammation

• Applicant: Privatdozent Dr. Walter Magerl
• Subject Area: Biological Psychiatry
• Term: from 2008 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 42860621

Focus of this project is the impact of the endocannabinoid system (ECS) on pain perception and pain plasticity in humans. For the second term of the Research Unit we propose the following experiments: We will continue to investigate the genotype-phenotype correlations of SNPs of the human CNR1, CNR2, FAAH, and DAGL genes in relation to a somatosensory phenotype and a model of human pain-LTP. Additionally, we will genotype a patient cohort scheduled for elective surgery (hysterectomy) to examine if the cannabinoid genotype contributes to the development of chronic postsurgical pain. CB1 receptors in cortical processing will be related to somatosensory profile and pain-LTP by positron emission tomography (PET) using the ligand [18F]MK9470. The role of cannabinoid lipids in regulation of neurogenic and non-neurogenic inflammation will be studied using the lipid palmitoyl ethanolamide (PEA) in 3 different human models of inflammation induced by high frequency electrical stimulation, noxious heat or ultraviolet B irradiation, which also vary in the contribution of peripheral versus central mechanisms of hyperalgesia. PEA acts on several receptor systems as well as increases the concentration of anandamide by down-regulating FAAH expression. Thus, in this part we will differentiate peripheral and central action of PEA on inflammation and hyperalgesia.

• DFG Programme: Research Units
• Subproject of: FOR 926: Physiology and Pathophysiology of the Endocannabinoid System
• Participating Person: Professor Dr. Rolf-Detlef Treede