The Role of Dopamine in Fronto-striatal Activation in Emotional-motivational Pain Processing in Patients With Chronic Pain

PR00P1_179697/1_3_4

Pain is a powerful motivator of behavior and it is more than the perception of nociceptive input. It is a complex experience that comprises different components: sensory discriminative, emotional-motivational and cognitive components. In chronic pain, a negative hedonic shift has been proposed that is characterized by disproportionally increased emotional-motivational compared to sensory-discriminative pain components. Such a negative hedonic shift is mirrored in a high comorbidity of chronic pain with affective disorders like depression and anxiety. However, the neurobiological mechanisms underlying such a negative hedonic shift i remain elusive. Animal work suggests an involvement of neuroinflammation, caused by chronic pain, which in turn is related to impaired release of the neurotransmitter dopamine. In line with this observation, impaired dopamine functioning has been described in chronic pain. Importantly, dopamine acts also as a neuromodulator, regulating functional connectivity between brain regions. Therefore, dysfunctional dopamine in chronic pain, possibly caused by neuroinflammation, might lead to altered blood oxygen level dependent (BOLD) response and functional connectivity. Correspondingly, altered functional connectivity in fronto-striatal brain networks has been shown to be predictive of transition from subacute to chronic pain. The aim of this study is to investigate the psychobiological mechanisms underlying the negative hedonic shift in chronic pain with a focus on the role of dopamine in functional connectivity of fronto-striatal brain networks, BOLD response of frontostriatal regions and their relation to heightened emotional-motivational pain processing.

2021-11-01

2023-07-31

2023-07-31

Completed

48

For fibromyalgia patients: Inclusion criteria: * Age between 18 to 70 years * Chronic widespread pain * Symptoms such as fatigue, cognitive dysfunction, and/or depressive symptoms * Sufficient knowledge of German or English to follow instructions * Ability to give written informed consent Exclusion criteria: * Psychiatric or neurological disorders, except depression and anxiety * Substance abuse or consumption of alcohol, illegal drugs, analgesics apart from prescribed routine medication within the last 24 h before testing session * Pacemaker or metal parts in the body or any contradictions to MRI * Pregnancy and breast-feeding * Medical history indicating any risk/allergies using the amisulpride or bromocriptine or both or other ergotamine. Long QT syndrome, cardiac arrhythmia, intake of drugs causing QT prolongation in the electrocardiogram. * Liver or/and kidney problems * High blood pressure or cardiovascular or heart disease * Stomach ulcers or bleeding * Fibrosis * Diabetes * Cancer patients * Intake of drugs lowering potassium levels in the blood * Blood pressure problems during pregnancy in the past * History of breast cancer in the family first-order relatives * Cerebrovascular events in anamnesis * Simultaneous intake of potent or moderate Cytochrome P450 inhibitors For Healthy participants: Inclusion criteria: * Age-matched healthy participants * Good overall health status * Sufficient knowledge of German or English to follow instructions * Ability to give written informed consent Exclusion criteria: * Pain longer than 3 consecutive days and on more than 30 days within the last 12 months * Major psychiatric or neurological disorders * Pregnancy and breast-feeding * Substance abuse or consumption of alcohol, illegal drugs, and analgesic drugs within 24 h before testing session * Pacemaker or metal parts in the body or any contradiction to MRI * Medical history indicating any risk/allergies using the amisulpride or bromocriptine or both or other ergotamine. * Liver or/and kidney problems * High blood pressure or cardiovascular or heart disease * Stomach ulcers or bleeding * Fibrosis * Diabetes * Low potassium levels in the blood * Blood pressure problems during pregnancy in the past * History of breast cancer in first-order relatives * Cerebrovascular events in anamnesis * Simultaneous intake of potent or moderate Cytochrome P450 inhibitors

{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'The drugs that will be used in this study will not be utilised as therapeutic clinical interventions, but as modulators of endogenous process and to assess psychobiological mechanisms in pain processing. Healthy controls will be administered with placebo or a dopamine agonist (bromocriptine) or a dopamine antagonist (amisulpride) on separate days to investigate the role of dopamine and fronto-striatal functional connectivity and BOLD response in relation to emotional-motivational component of pain. Fibromyalgia patients receive only placebo or a dopamine agonist to see the effects of normalization of dopamine on fronto-striatal connectivity and BOLD response, because a lowered dopamine level is assumed to decrease the emotional-motivational component of pain.', 'primaryPurpose': 'BASIC_SCIENCE', 'maskingInfo': {'masking': 'DOUBLE', 'maskingDescription': 'Double-blinded randomized placebo-controlled between-within-subject cross-over design with repeated measures; Participants and experimenter will be blinded through out the complete data collection. In addition, participants are not fully instructed about the purpose of the specific tests during the test session, but will be debriefed after final testing session.', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 48, 'type': 'ACTUAL'}}

2023-09-07