Human Evidence of a Supra-Spinal Modulating Role of Dopamine on Pain Perception

Background: Over the last decades, remarkable progresses have been accomplished regarding the understanding of the neurophysiologic and neuropharmacological bases of pain. A growing preclinical literature supports a role for substance P, endogenous opioids, glutamate, serotonin, and norepinephrine in pain perception. Recently, a series of studies explored the function of dopamine in pain perception, which we review here, while focusing on human studies. Methods: The literature was screened using electronic databases. Results: We found evidence from genetics, brain imaging, neuropsychiatry, and pharmacology of an involvement of dopamine in pain processing. Using positron emission tomography and molecular genetics, studies have been performed in healthy volunteers and patients suffering from chronic pain conditions, showing a key role of dopamine in pain perception. Moreover, abnormal pain perception has been documented in neuropsychiatric disorders, such as Parkinson's disease and schizophrenia, where dopamine has a pathophysiological role. Lastly, pharmacological studies have shown that dopaminergic drugs (antipsychotics, antiparkinsonian drugs, atypical antidepressants, psychostimulants) modify pain perception. Discussion: Although there is growing evidence supporting a role of dopamine in pain perception, the mechanisms by which dopamine influences pain processing remains to be determined. On the basis of preliminary findings, we put forth the hypothesis that dopamine is involved in endogenous pain modulation systems, and further discuss the implications of this hypothesis for the understanding of the physiopathology of chronic pain disorders associated with dysfunctional endogenous pain modulation systems. Synapse 63:390-402, 2009. (C) 2009 Wiley-Liss, Inc.