Enhanced excitatory and reduced inhibitory synaptic transmission contribute to persistent pain-induced neuronal hyper-responsiveness in anterior cingulate cortex.
The anterior cingulate cortex (ACC) has been demonstrated to play an important role in the affective dimension of pain. Although much evidence has pointed to an increased excitatory synaptic transmission in the ACC in some of the pathological pain state, the inhibitory synaptic transmission in this process has not been well studied. Also, the overall changes of excitatory and inhibitory synaptic transmission have not been comparatively studied in an animal model displaying both long-term persistent nociception and hyperalgesia. Here we used patch clamp recordings in ACC brain slices to observe the changes in synaptic transmission in a pain model induced by peripheral bee venom injection. First, we show that, comparing with those of naive and saline controlled rats, there was a significant increase in spike frequency in ACC neurons harvested from rats after 2 h period of peripheral persistent painful stimuli. Second, it is further shown that the frequency, amplitude and half-width were all increased in spontaneous excitatory post-synaptic currents (sEPSCs), while the amplitude of spontaneous inhibitory post-synaptic currents (sIPSCs) was decreased. The recordings of miniature post-synaptic currents demonstrate an increase in frequency of miniature excitatory post-synaptic currents (mEPSCs) and a decrease in both frequency and amplitude of miniature inhibitory post-synaptic currents (mIPSCs) in rats' ACC slice of bee venom treatment. Taken together, the present results demonstrate an unparalleled change between excitatory and inhibitory synaptic transmission in the ACC under a state of peripheral persistent nociception that might be underlying mechanisms of the excessive excitability of the ACC neurons. We propose that the painful stimuli when lasts or becomes persistent may cause a disruption of the balance between excitatory and inhibitory synaptic transmission that can contribute to the functional change in the ACC.
Gong
K-R
KR
Institute for Biomedical Sciences of Pain, Capital Medical University, Beijing 100069, PR China.
Cao
F-L
FL
He
Y
Y
Gao
C-Y
CY
Wang
D-D
DD
Li
H
H
Zhang
F-K
FK
An
Y-Y
YY
Lin
Q
Q
Chen
J
J
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001514:Bee Venoms / Q000009:adverse effects / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001703:Biophysics / Q000379:methods; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000473:pathology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D010146:Pain / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D001514:Bee Venoms; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001640:Bicuculline