pain; dopamine; fibromyalgia; reward; positron emission tomography
Kuhn F. P., Warnock G. I., Burger C., Ledermann K., Martin-Soelch C., Buck A. (2014), Comparison of PET template-based and MRI-based image processing in the quantitative analysis of C11-raclopride PET., in EJNMMI Res
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Ledermann K., Jenewein J., Sprott H., Hasler G., Schnyder U., Burger C., Johayem A., Cservenyak T., Kollias S., Buck A., Martin-Soelch C. (2013), A common neurobiology for reward, chronic pain and depression? A [11C]raclopride bolus plus constant infusion PET-study, in European Neuropsychopharmacology
, 23(2), 354.
Martin-Soelch C, Ledermann K., Jenewein J, Hasler G, Schnyder U., Burger C., Johayem A., Cservenyak T, Kollias A, Buck A, Sprott H. (2011), Is Fibromyalgia a neuropathic pain disease?, in European Journal of Pain
, Supp. 5(1), 231.
Background: Recent findings suggest that pain and reward are mediated by similar neural pathways in the central nervous system, and that these pathways are related to both the dopamine (DA) and the opioid system. It is well documented that DA is involved in the processing of rewarding information, and several findings point to a role of DA in pain regulation. However, the exact role of DA in the perception of pain and pain relief is still unknown. A dysfunction of the central DA system was evidenced in chronic pain patients, including patients with neuropathic pain and patients with fibromyalgia (FMS). Additionally, there is extensive comorbidity between chronic pain and depression, which often includes anhedonia, i.e. the reduced ability to enjoy pleasurable activities. Anhedonia has been hypothesized to be related to a hypofunction of the DA system that could affect the neural processing of rewarding information. Finally, the neuropathology of FMS is still poorly understood and the role of the observed reduction in DA presynaptic function in the pathophysiology of FMS is unclear. The main aim of this project is to investigate the modulation of pain perception and pain relief by dopamine (DA) in patients with FMS compared to healthy controls using the [11C] raclopride PET method. A second aim is to investigate whether the DA response to rewarding stimuli can differentiate between FMS patients with and without depression in order to understand whether an alteration of the neural responses to reward could contribute to the depressive symptoms that are often associated with FMS.Working hypothesis: We hypothesize 1) that FMS patients will show a reduced DA function that will be associated with increased pain perception and reduced positive feelings associated with pain relief, and 2) that FMS patients will show reduced DA release in response to unpredictable monetary rewards compared to healthy controls and that this reduction will be more accentuated in the group of FMS patients with depression than in the FMS patients without depression.Experimental design/methods: We plan to correlate on one hand basic DA2 receptor binding with the subjective ratings of pain and pain relief related to the administration of painful thermal stimulation, and on the other hand to measure the endogeneous DA release associated to unpredictable monetary rewards during bolus-plus-infusion [11C] raclopride PET scanning, while simultaneously assessing mood and pain ratings in 20 healthy subjects, 20 subjects meeting the criteria for FMS without psychiatric comorbidity, and 20 subjects meeting the criteria for FMS and the criteria for major depressive disorder (MDD).Expected value: This study is clinically relevant because it will provide new insights on the neural correlates of FMS, which are still poorly understood. FMS is related to high direct and indirect costs, but is still difficult to treat. Based on first evidence showing an involvement of DA in pain and a dysfunction of the DA function in patients with FMS, we believe to be able to bring a better understanding of the role of pain modulation by the DA system in the neuropathophysiology of FMS. This study is innovative and original because it addresses the question of the association between altered pain processing and depression in FMS by investigating potential common neural bases. This project is multidisciplinary and uses a modern method that allows in vivo imaging of the DA function in the human brain in response to motivational stimuli. Finally, we are confident that our results will both bring a better understanding of FMS as well as open new treatment perspectives, highlighting the role of DA in this condition.