ReviewStriatal dopamine D2 receptors in modulation of pain in humans: a review
Introduction
The basal ganglia consist of four main nuclei (the striatum, the globus pallidus, the subthalamic nucleus and the substantia nigra), which provide a major link between the thalamus and the cerebral cortex. These nuclei receive multimodal input from all sensory systems providing a gating station for continuous sensory information, including pain. Dysfunctions of the basal ganglia result in movement disorders indicating an important role in motor control. Depletion of dopamine in the nigrostriatal dopaminergic neurons leads to impaired movement as occurs in Parkinson’s disease. The dopaminergic system in the basal ganglia has also been implicated in attention, cognition, and stress (Kaasinen and Rinne, 2002, Kandel et al., 2000, Nieoullon, 2002, Pani et al., 2000). Although less intensively studied, the basal ganglia also appear to have a role in pain (for a comprehensive review, see the work of Chudler and Dong, 1995). In this review, we present evidence suggesting that particularly the striatum, consisting of the putamen and the caudate nucleus, and the striatal dopamine D2 receptor may have a significant role in the modulation of pain sensation both in experimental and clinical conditions.
Section snippets
Experimental animal studies
Animal studies suggest that the basal ganglia play a major role in the processing of somatosensory information including noxious stimuli (Chudler and Dong, 1995). Neurons in the substantia nigra and striatum respond to noxious thermal (Chudler, 1998, Barasi, 1979, Pay and Barasi, 1982), mechanical (Chudler, 1998, Chudler et al., 1993, Schultz and Romo, 1987) and electrical stimulation (Bernard et al., 1992, Gao et al., 1990). Electrical and chemical lesions of nigrostriatal neurons have been
Striatal dopamine is involved in pain regulation
Striatal dopamine may have an important role in pain regulation also in humans. This is suggested by the clinical observation that pain is a frequent symptom in degenerative diseases of the nigrostriatal dopaminergic system such as Parkinson's disease (Ford, 1998, Goetz et al., 1986, Witjas et al., 2002). Burning sensations characteristic of central pain have been reported in patients with Parkinson's disease (Ford et al., 1996, Koller, 1984, Schott, 1985, Snider et al., 1976, Witjas et al.,
Potential implications
Positron emission tomography studies in healthy subjects and in patients with chronic orofacial pain indicate that the nigrostriatal dopaminergic system and striatal dopamine D2 receptors may have an important role in the regulation of experimental and pathophysiological pain. According to these findings, the analgesic effect of dopaminergic compounds may, at least partly, be explained by their action on striatal dopamine D2 receptors. Imaging of striatal dopamine D2 receptors might not only
Acknowledgements
The authors were supported by the Turku University Central Hospital (EVO-funding), Turku, the Finnish Association for the Study of Pain, Helsinki, the Finnish Medical Society Duodecim, Helsinki, the Sigrid Jusélius Foundation, Helsinki, the Academy of Finland, Helsinki, the Finnish Dental Society, Helsinki, Finland and the Lundbeck Foundation, Hellerup, Denmark.
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