NMDA receptors in the anterior cingulate cortex mediate pain-related aversion

Lei, Liugen; Sun, Shan; Gao, Yong‐Jing; Zhao, Zhi‐Qi; Zhang, Yu‐Qiu

doi:10.1016/j.expneurol.2004.06.012

Cited by 69 publications

(39 citation statements)

References 48 publications

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“…The present results differ from those of another study showing, in particular, an absence of effects of another NMDA antagonist (AP5) on inflammatory pain levels after administration in the anterior cingulate cortex 43. In contrast, we found that administration of a NR2B antagonist before formalin injection reduced pain intensity.…”

Section: Discussioncontrasting

confidence: 99%

Cortical NR2B NMDA subunit antagonism reduces inflammatory pain in male and female rats

Quintero

Herrera²,

Bethancourt³

2011

JPR

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BackgroundStudies have shown that N-methyl-D-aspartate (NMDA) receptors play a critical role in pain processing at different levels of the central nervous system.MethodsIn this study, we used adult Wistar rats to examine gender differences in the effects of NR2B NMDA antagonism at the level of the anterior cingulate cortex in phasic pain, and in the first and second phases of a formalin test. Rats underwent stereotactic surgery for cannula implantation in the anterior cingulate cortex. After recovery, paw withdrawal latency to a noxious thermal stimulus was assessed. Rats were also subjected to a formalin pain test whereby 60 μL of 5% formalin was injected into the right hind paw.ResultsFemale and male rats that received Ro 25-6981, an NR2B antagonist, before formalin injection showed significantly reduced pain responses to the formalin test compared with saline-injected control rats (P < 0.05). No gender differences in phasic pain responses were found in rats treated with Ro 25-6981.ConclusionThese results suggest that cortical antagonism of the NR2B subunit reduces inflammatory pain levels in both genders of rat.

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Section: Discussioncontrasting

confidence: 99%

Cortical NR2B NMDA subunit antagonism reduces inflammatory pain in male and female rats

Quintero

Herrera²,

Bethancourt³

2011

JPR

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“…One dose of antagonist was applied to each CRD-excited neuron. The doses of AP5 and CNQX were chosen in accordance with previous studies, which showed that similar doses of glutamate receptors antagonists inhibited ACC laminar transmembrane currents (layer II/III and layer V) during noxious electrical stimulation of medial thalamus (53) and suppressed pain-related aversion (23), avoidance (27a), and visceral pain responses in rats (5).…”

Section: Experimental Designmentioning

confidence: 98%

Role for NMDA receptors in visceral nociceptive transmission in the anterior cingulate cortex of viscerally hypersensitive rats

Gao

Jin

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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We have identified colorectal distension (CRD)-responsive neurons in the anterior cingulate cortex (ACC) and demonstrated that persistence of a heightened visceral afferent nociceptive input to the ACC induces ACC sensitization. In the present study, we confirmed that rostral ACC neurons of sensitized rats [induced by chicken egg albumin (EA)] exhibit enhanced spike responses to CRD. Simultaneous in vivo recording and reverse microdialysis of single ACC neurons showed that a low dose of glutamate (50 microM) did not change basal ACC neuronal firing in normal rats but increased ACC neuronal firing in EA rats from 18 +/- 2 to 32 +/- 3.8 impulses/10 s. A high dose of glutamate (500 microM) produced 1.95-fold and a 4.27-fold increases of ACC neuronal firing in sham-treated rats and in EA rats, respectively, suggesting enhanced glutamatergic transmission in the ACC neurons of EA rats. Reverse microdialysis of the 3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainite receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM) reduced basal and abolished CRD-induced ACC neuronal firing in normal rats. In contrast, microdialysis of N-methyl-d-aspartate (NMDA) receptor antagonist AP5 had no effect on ACC neuronal firing in normal rats. However, AP5 produced 86% inhibition of ACC neuronal firing evoked by 50 mmHg CRD in the EA rats. In conclusion, ACC nociceptive transmissions are mediated by glutamate AMPA receptors in the control rats. ACC responses to CRD are enhanced in viscerally hypersensitive rats. The enhancement of excitatory glutamatergic transmission in the ACC appears to mediate this response. Furthermore, NMDA receptors mediate ACC synaptic responses after the induction of visceral hypersensitivity.

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“…In addition, while some areas in Table 3 were only identified in a few studies (e.g., habenula, ACC), it should be noted that this is likely due to the stringent inclusion/exclusion criteria applied in the present investigation (e.g., the use of passive perception of aversive stimuli; studies involving metabolic indicators or imaging only). For example, the ACC’s inclusion here is also supported by a number of studies using painful aversive stimuli which robustly activate the ACC (Lei et al, 2004a,b; Li et al, 2009). Nonetheless, areas such as the habenula were included in Figure 2 as being potentially good candidates (identified in light beige) for the core aversion-related network as emerging data from animal studies in non-human primates (Matsumoto and Hikosaka, 2009a) and rodents (Roseboom et al, 2007) and some studies in humans (Salas et al, 2010), have indicated its involvement in the processing of aversive stimuli.…”

Section: Discussionmentioning

confidence: 73%

Identifying a Network of Brain Regions Involved in Aversion-Related Processing: A Cross-Species Translational Investigation

Hayes

Northoff

2011

Front. Integr. Neurosci.

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The ability to detect and respond appropriately to aversive stimuli is essential for all organisms, from fruit flies to humans. This suggests the existence of a core neural network which mediates aversion-related processing. Human imaging studies on aversion have highlighted the involvement of various cortical regions, such as the prefrontal cortex, while animal studies have focused largely on subcortical regions like the periaqueductal gray and hypothalamus. However, whether and how these regions form a core neural network of aversion remains unclear. To help determine this, a translational cross-species investigation in humans (i.e., meta-analysis) and other animals (i.e., systematic review of functional neuroanatomy) was performed. Our results highlighted the recruitment of the anterior cingulate cortex, the anterior insula, and the amygdala as well as other subcortical (e.g., thalamus, midbrain) and cortical (e.g., orbitofrontal) regions in both animals and humans. Importantly, involvement of these regions remained independent of sensory modality. This study provides evidence for a core neural network mediating aversion in both animals and humans. This not only contributes to our understanding of the trans-species neural correlates of aversion but may also carry important implications for psychiatric disorders where abnormal aversive behavior can often be observed.

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NMDA receptors in the anterior cingulate cortex mediate pain-related aversion

Cited by 69 publications

References 48 publications

Cortical NR2B NMDA subunit antagonism reduces inflammatory pain in male and female rats

Cortical NR2B NMDA subunit antagonism reduces inflammatory pain in male and female rats

Role for NMDA receptors in visceral nociceptive transmission in the anterior cingulate cortex of viscerally hypersensitive rats

Identifying a Network of Brain Regions Involved in Aversion-Related Processing: A Cross-Species Translational Investigation

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