Membrane potential synchrony of neurons in anterior cingulate cortex plays a pivotal role in generation of neuropathic pain

Abstract

The pathophysiology of neuropathic pain generation has not been fully investigated. Previous studies have primarily focused on changes in the properties of single neurons in the brain after nerve injury; however, little is known concerning the role of neuron-to-neuron connections in neuropathic pain pathogenesis. Synaptic transmission potentiation in anterior cingulate cortex (ACC) has been confirmed to be responsible for the formation of neuropathic pain. Thus, analysis of interneuronal connections in the ACC is an important approach for understanding the mechanism of neuropathic pain since it provides information on the potency of synaptic transmission. Here, we recorded membrane potentials from pairs of ACC neurons in anaesthetised rats and found that cross-correlations between pairs of ACC neurons significantly increased after surgery for chronic constriction injury (CCI). Moreover, CCI surgery could also enhance the power spectrum density of lower and higher-frequency membrane oscillations while having no effect on middle-frequency oscillations. The activation of membrane potential synchrony and power spectrum was reversed by the electrical synapse blocker mefloquine and pain behaviour was simultaneously alleviated. Our results may indicate that activation of membrane potential synchrony contributes to generation of neuropathic pain.

Pain-Relieving Effects of mTOR Inhibitor in the Anterior Cingulate Cortex of Neuropathic Rats

“…Because both the ACC and primary somatosensory cortex, which are located in the pain ascending pathway, receive nociceptive inputs from the medial thalamus, the increased activity of pyramidal cells in both areas reflects their participation in a cerebral cortical circuit involved in chronic pain. In fact, electrophysiological studies show the activation of many pyramidal neurons of ACC layer II/III after nerve injury [ 59 , 60 ], and some studies show that inhibiting the hyperactivity or plasticity of pyramidal neurons in the ACC lessens the development of chronic pain [ 59 , 61 ]. Combining our current results with those of previous studies, we speculated that rapamycin modulates the interaction between GluA1-PSD-95 and NR2B-PSD-95 by regulating the mTOR signaling pathway that controls synaptic plasticity in the ACC.…”

Effect of Electroacupuncture on Pain Perception and Pain-Related Affection: Dissociation or Interaction Based on the Anterior Cingulate Cortex and S1

“…Researchers [ 32 ] further proved that the ACC was a brain region closely linked to pain-related emotions. It has been found that the long-term enhancement of ACC activity may be one of the mechanisms of persistent emotional change in patients with chronic pain caused by nerve injury or peripheral inflammation [ 33 – 36 ]. Our data showed that the PWT of the model group was significantly lower than that of the control group at 16 d. The group with the ACC lesion did not differ from the control group at 16 d. However, the pain-related aversion developed from 2 d to 16 d, and there was no manifestation of aversion after ACC lesioning.…”

Role of mu-opioid receptor in nociceptive modulation in anterior cingulate cortex of rats

“…Studies in recent years have found that there is a close relationship between the ACC and neuropathic pain. 7,[10][11][12][23][24][25] Neuropathic pain model was set up by chronic constriction injury of the left sciatic nerve of rats. The left HWL to thermal and mechanical stimulation, by hot plate and Randall Selitto Test respectively, were used to evaluate the antinociception.…”