Striatal dopamine D2 receptors in modulation of pain in humans: a review

doi:10.1016/j.ejphar.2004.07.024

European Journal of Pharmacology

Volume 500, Issues 1–3, 1 October 2004, Pages 187-192

https://doi.org/10.1016/j.ejphar.2004.07.024 Get rights and content

Abstract

We review evidence indicating that the striatum and striatal dopamine D2 receptors are involved in the regulation of pain in humans. Painful stimulation produces an increase in regional cerebral blood flow in the human striatum. Pain is a common symptom in patients with nigrostriatal dopaminergic hypofunction. Positron emission tomography findings show that a low dopamine D2 receptor availability in the striatum of healthy subjects (indicating either a low density of dopamine D2 receptors or a high synaptic concentration of dopamine) is associated with a high cold pain threshold and a low capacity to recruit central pain inhibition by conditioning stimulation. Patients with chronic orofacial pain have higher dopamine D2 receptor availability than their age-matched controls. We propose that the striatal dopamine D2 receptor may be an important target for the diagnosis and treatment of chronic pain.

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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ReviewStriatal dopamine D2 receptors in modulation of pain in humans: a review

Abstract

Introduction

Section snippets

Experimental animal studies

Striatal dopamine is involved in pain regulation

Potential implications

Acknowledgements

Brain Res.

Life Sci.

Pain

Brain Res.

Pain

Pain

NeuroImage

Pain

Pain

Brain Res.

Pain

Pain

Pain

Pain

Pain

Pain

Neurosci. Biobehav. Rev.

Exp. Neurol.

Brain Res.

J. Affect. Disord.

Eur. J. Pharmacol.

Prog. Neurobiol.

Pharmacol. Biochem. Behav.

Prog. Neurobiol.

Pain

Brain Res.

Pain

Eur. J. Pharmacol.

Dopamine D2 receptors in normal human brain: effect of age measured by positron emission tomography (PET) and [11C]-raclopride

Ann. N.Y. Acad. Sci.

An explanation for reflex blink hyperexcitability in Parkinson’s disease: II. Nucleus raphe magnus

J. Neurosci.

An explanation for reflex blink hyperexcitability in Parkinson's disease: I. Superior colliculus

J. Neurosci.

Nucleus centralis of the amygdala and the globus pallidus ventralis: electrophysiological evidence for an involvement in pain processes

J. Neurophysiol.

Apomorphine-induced yawning in migraine patients: enhanced responsiveness

Clin. Neuropharmacol.

Monoamines in the brain cerebrospinal fluid of facial pain patients

Anesth. Prog.

Comparison of human cerebral activation pattern during cutaneous warmth, heat pain, and deep cold pain

J. Neurophysiol.

Review
Striatal dopamine D2 receptors in modulation of pain in humans: a review

Dopamine D2 receptors in normal human brain: effect of age measured by positron emission tomography (PET) and [¹¹C]-raclopride