The Role of Mesostriatal Dopamine System and Corticostriatal Glutamatergic Transmission in Chronic Pain

Published on Oct 1, 2021in Brain Sciences3.394
· DOI :10.3390/BRAINSCI11101311
Barbara Ziółkowska15
Estimated H-index: 15
(PAN: Polish Academy of Sciences)
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.
#1Thomas C. Jhou (MUSC: Medical University of South Carolina)H-Index: 15
Between 2005 and 2009, several research groups identified a strikingly dense inhibitory input to midbrain dopamine neurons arising from a previously uncharted region posterior to the ventral tegmental area (VTA). This region is now denoted as either the rostromedial tegmental nucleus (RMTg) or the "tail of the VTA" (tVTA), and is recognized to express distinct genetic markers, encode negative "prediction errors" (inverse to dopamine neurons), and play critical roles in behavioral inhibition and ...
#1Wen-Jie Ren (NU: Northwestern University)H-Index: 13
#2Maria Virginia Centeno (NU: Northwestern University)H-Index: 17
Last. D. James Surmeier (NU: Northwestern University)H-Index: 96
view all 7 authors...
ABSTRACT The nucleus accumbens (NAc) and the ventral tegmental area (VTA) are critical hubs in the brain circuitry controlling chronic pain. Yet, how these 2 regions interact to shape the chronic pain state is poorly understood. Our studies show that in mice, spared nerve injury (SNI) induced alterations in the functional connectome of D2-receptor expressing spiny projection neurons in the core region of the NAc-enhancing connections with prelimbic cortex and weakening them with basolateral amyg...
#1Fernanda Vergara (UFPR: Federal University of Paraná)H-Index: 2
#2Natalia F. Sardi (UFPR: Federal University of Paraná)H-Index: 6
Last. Luana Fischer (UFPR: Federal University of Paraná)H-Index: 15
view all 7 authors...
Abstract Decreased dopaminergic activity and increased kappa opioid activity in the mesolimbic system underlie the negative emotional states related to chronic pain. However, it is not known whether these changes are just consequence of chronic pain or contribute to the sensorial changes associated with chronic pain. In this study, we asked whether the mesolimbic dopamine and kappa opioid systems contribute to the development and maintenance of chronic hyperalgesia, one of the most common sensor...
#1Amie L. Severino (Semel Institute for Neuroscience and Human Behavior)H-Index: 7
#2Nitish Mittal (University of Texas at Austin)H-Index: 7
Last. Wendy Walwyn (UCLA: University of California, Los Angeles)H-Index: 24
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Abstract μ-Opioid receptors (MORs) are densely expressed in different brain regions known to mediate reward. One such region is the striatum where MORs are densely expressed, yet the role of these MOR populations in modulating reward is relatively unknown. We have begun to address this question by using a series of genetically engineered mice based on the Cre recombinase/loxP system to selectively delete MORs from specific neurons enriched in the striatum: dopamine 1 (D1) receptors, D2 receptors...
#1Shi-Hao Gao (Third Military Medical University)H-Index: 3
#2Lin-Lin Shen (Third Military Medical University)H-Index: 15
Last. Huai-Zhen Ruan (Third Military Medical University)H-Index: 7
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Although the anterior cingulate cortex (ACC) plays a vital role in neuropathic pain-related aversion, the underlying mechanisms haven't been fully studied. The mesolimbic dopamine system encodes reward and aversion, and participates in the exacerbation of chronic pain. Therefore, we investigated whether the ACC modulates aversion to neuropathic pain via control of the mesolimbic dopamine system, in a rat model of chronic constriction injury (CCI) to the sciatic nerve. Using anterograde and retro...
#1Meena M. MakaryH-Index: 7
#2Pablo Polosecki (IBM)H-Index: 5
Last. Paul Geha (UR: University of Rochester)H-Index: 22
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Chronic pain is a highly prevalent disease with poorly understood pathophysiology. In particular, the brain mechanisms mediating the transition from acute to chronic pain remain largely unknown. Here, we identify a subcortical signature of back pain. Specifically, subacute back pain patients who are at risk for developing chronic pain exhibit a smaller nucleus accumbens volume, which persists in the chronic phase, compared to healthy controls. The smaller accumbens volume was also observed in a ...
This paper examines the development of and some logistical and methodological issues surrounding the use of animal models of chronic pain. The first section addresses the emergent move towards mechanism-based and disease-related animal models of chronic pain that has accelerated since the late 1980s following publication of Bennett and Xie’s (Pain 33:87–107, 1998) paper on chronic constriction injury of the sciatic nerve and Stein et al.’s (Pharmacol Biochem Behav 31:445–451, 1988) paper on unil...
#1Agnieszka Wawrzczak-Bargiela (PAN: Polish Academy of Sciences)H-Index: 14
#2Barbara Ziółkowska (PAN: Polish Academy of Sciences)H-Index: 15
Last. Ryszard Przewlocki (PAN: Polish Academy of Sciences)H-Index: 56
view all 8 authors...
Disturbances in the function of the mesostriatal dopamine system may contribute to the development and maintenance of chronic pain, including its sensory and emotional/cognitive aspects. In the present study, we assessed the influence of chronic constriction injury (CCI) of the sciatic nerve on the expression of genes coding for dopamine and opioid receptors as well as opioid propeptides in the mouse mesostriatal system, particularly in the nucleus accumbens. We demonstrated bilateral increases ...
#1Dana E. Selley (VCU: Virginia Commonwealth University)H-Index: 51
#2Matthew F. Lazenka (VCU: Virginia Commonwealth University)H-Index: 10
Last. S. Stevens Negus (VCU: Virginia Commonwealth University)H-Index: 32
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Abstract Neuropathy is major source of chronic pain that can be caused by mechanically or chemically induced nerve injury. Intraplantar formalin injection produces local necrosis over a two-week period and has been used to model neuropathy in rats. To determine whether neuropathy alters dopamine (DA) receptor responsiveness in mesolimbic brain regions, we examined dopamine D1-like and D2-like receptor (D1/2R) signaling and expression in male rats 14 days after bilateral intraplantar formalin inj...
#1Casey A. Mussio (WSU: Wayne State University)H-Index: 1
#2Steven E. Harte (UM: University of Michigan)H-Index: 25
Last. George S. Borszcz (WSU: Wayne State University)H-Index: 13
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Abstract The anterior cingulate cortex (ACC) modulates emotional responses to pain. Whereas, the caudal ACC (cACC) promotes expression of pain affect, the rostral ACC (rACC) contributes to its suppression. Both subdivisions receive glutamatergic innervation, and the present study evaluated the contribution of NMDA receptors within these subdivisions to rats’ expression of pain affect. Vocalizations that follow a brief noxious tail shock (vocalization afterdischarges, VAD) are a validated rodent ...
Cited By0
#1Nicole Mercer Lindsay (UNC: University of North Carolina at Chapel Hill)
#2Chong Chen (UNC: University of North Carolina at Chapel Hill)
Last. Grégory Scherrer (UNC: University of North Carolina at Chapel Hill)H-Index: 2
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Pain is a multidimensional experience with sensory-discriminative, affective-motivational, and cognitive-evaluative components. Pain aversiveness is one principal cause of suffering for patients wi...
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