NMDA NR2A and NR2B receptors in the rostral anterior cingulate cortex contribute to pain-related aversion in male rats.
NMDA receptors, which are implicated in pain processing, are highly expressed in forebrain areas including the anterior cingulate cortex (ACC). The ACC has been implicated in the affective response to noxious stimuli. Using a combination of immunohistochemical staining, Western blot, electrophysiological recording and formalin-induced conditioned place avoidance (F-CPA) rat behavioral model that directly reflects the affective component of pain, the present study examined formalin nociceptive conditioning-induced changes in the expressions of NMDA receptor subunits NR1, NR2A, and NR2B in the rostral ACC (rACC) and its possible functional significance. We found that unilateral intraplantar (i.pl.) injection of dilute formalin with or without contextual conditioning exposure markedly increased the expressions of NMDA receptor subunits NR2A and NR2B but not of NR1 in the bilateral rACC. NMDA-evoked currents in rACC neurons were significantly greater in formalin-injected rats than in naïve or normal saline-injected rats. Selectively blocking either NR2A or NR2B subunit in the rACC abolished the acquisition of F-CPA and formalin nociceptive conditioning-induced Fos expression, but it did not affect formalin acute nociceptive behaviors and non-nociceptive fear stimulus-induced CPA. These results suggest that both NMDA receptor subunits NR2A and NR2B in the rACC are critically involved in pain-related aversion. Thus, a new strategy targeted at NMDA NR2A or NR2B subunit might be raised for the prevention of pain-related emotional disturbance.
Li
Ting-Ting
TT
Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Ren
Wen-Hua
WH
Xiao
Xiao
X
Nan
Jia
J
Cheng
Long-Zhen
LZ
Zhang
Xue-Han
XH
Zhao
Zhi-Qi
ZQ
Zhang
Yu-Qiu
YQ
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000503:physiopathology*; D004594:Electrophysiology; D005239:Fear / Q000523:psychology; D005557:Formaldehyde; D007839:Functional Laterality / Q000502:physiology; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D008297:Male; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology* / Q000523:psychology*; D010147:Pain Measurement / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology*
D007202:Indicators and Reagents; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D020320:Oligoribonucleotides, Antisense; D016194:Receptors, N-Methyl-D-Aspartate; D005557:Formaldehyde
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