Abstract
There is increasing recognition of the involvement of the nigrostriatal and mesolimbic dopamine systems in the modulation of chronic pain. The first part of the present article reviews the evidence indicating that dopamine exerts analgesic effects during persistent pain by stimulating the D2 receptors in the dorsal striatum and nucleus accumbens (NAc). Thereby, dopamine inhibits striatal output via the D2 receptor-expressing medium spiny neurons (D2-MSN). Dopaminergic neurotransmission in the mesostriatal pathways is hampered in chronic pain states and this alteration maintains and exacerbates pain. The second part of this article focuses on the glutamatergic inputs from the medial prefrontal cortex to the NAc, their activity changes in chronic pain, and their role in pain modulation. Finally, interactions between dopaminergic and glutamatergic inputs to the D2-MSN are considered in the context of persistent pain. Studies using novel techniques indicate that pain is regulated oppositely by two independent dopaminergic circuits linking separate parts of the ventral tegmental area and of the NAc, which also interact with distinct regions of the medial prefrontal cortex.
Highlights
Pharmacological studies involving injections of dopamine receptor ligands into the dorsal striatum (dStr) and nucleus accumbens (NAc) suggest that stimulation of the D2 receptor (D2R) exerts an analgesic effect, whereas the striatal D1 receptor (D1R) plays no role in pain
By a local administration of a GABAA receptor antagonist blocked aversion elicited by enhanced input from the anterior cingulate cortex (ACC). These results suggest that, in chronic pain, stimulation of the GABAergic neurons in the ventral tegmental area (VTA) by the overactive input from the ACC contributes to the pain-related aversion but not sensory hypersensitivity [85]
The basic view of chronic pain as a hypodopaminergic state emerged from experiments involving stimulation or lesions of the mesencephalic dopaminergic neurons, injections of dopamine receptor ligands into the dStr and NAc in rodent models of pain, as well as human brain imaging studies in chronic pain conditions and observations of pain symptom profiles in Parkinson’s disease (PD)
Summary
Chronic pain is a common condition, which affects nearly 20% of people in Western societies. Is most likely due to maladaptive plastic changes in the central nervous system (CNS), which develop in response to prolonged nociceptive stimulation resulting from an initial injury, inflammation, or other diseases that damage peripheral tissues and/or parts of the somatosensory nervous system. Such morbid neural plasticity is probably responsible for the continuation of painful sensations even after the initial lesion has healed, underlying the occurrence and persistence of such symptoms as spontaneous pain, hyperalgesia (increased sensitivity to nociceptive stimuli), and allodynia (pain in response to stimuli which are normally innocuous, e.g., touch) [8].
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