Intracortical Circuits in Rat Anterior Cingulate Cortex Are Activated by Nociceptive Inputs Mediated by Medial Thalamus

Abstract

We investigated the afferents and intracortical synaptic organization of the anterior cingulate cortex (ACC) during noxious electrical stimulation. Extracellular field potentials were recorded simultaneously from 16 electrodes spanning all layers of the ACC in male Sprague-Dawley rats anesthetized by halothane inhalation. Laminar-specific transmembrane currents were calculated with the current source density analysis method. Two major groups of evoked sink currents were identified: an early group (latency = 54.04 +/- 2.12 ms; 0.63 +/- 0.07 mV/mm(2)) in layers V-VI and a more intense late group (latency = 80.07 +/- 4.85 ms; 2.16 +/- 0.22 mV/mm(2)) in layer II/III and layer V. Multiunit activities were evoked mainly in layer V and deep layer II/III with latencies similar to that of the early and late sink groups. The evoked EPSP latencies of pyramidal neurons in layers II/III and V related closely with the sink currents. The sink currents were inhibited by intracortical injection of CNQX (1 mM, 1 microl), a glutaminergic receptor antagonist, and enhanced by intraperitoneal (5 mg/kg) and intracortical (10 microg/microl, 1 microl) injection of morphine, a mu-opioid receptor agonist. Paired-pulse depression was observed with interpulse intervals of 50 to 1,000 ms. High-frequency stimulation (100 Hz, 11 pulses) enhanced evoked responses in the ACC and evoked medial thalamic (MT) unit activities. MT lesions blocked evoked responses in the ACC. Our results demonstrated that two distinct synaptic circuits in the ACC were activated by noxious stimuli and that the MT is the major thalamic relay that transmits nociceptive information to the ACC.

Metabolic Abnormalities in Pain-Processing Regions of Patients with Fibromyalgia: A 3T MR Spectroscopy Study

“…30 There are many studies on the implication of Glu in nociception. [31][32][33] In particular, an increase of Glu at the level of anterior cingulate cortex was demonstrated by Mullins et al 34 in association with painful stimuli, and these variations correlated with the perceived pain intensity. Our results confirm this glutamatergic alteration, and the increase of Glx/Cr and Glu/Cr in both VLPFCs and not in thalami adds new insight into the physiopathology.…”

Cerebral cortex modulation of pain

“…Intraperitoneal and intracortical injections of morphine enhanced the sink currents in the ACC evoked by noxious electrical stimuli [24] . However, studies in patients with predominantly post-stroke pain demonstrated that there is significantly less opioid receptor binding in ACC [36,37] .…”

“…The mRNA expression level of metabotropic glutamate receptor 3 (mGluR3) is significantly increased in cortical areas of monoarthritic rats, including the contralateral cingulate cortex [32] . Intracortical injection of glutaminergic receptor antagonist inhibited the sink currents in the ACC evoked by noxious electrical stimuli [24] . Consistent with this finding, chemical activation of the NMDA receptor or mGluR in the ACC decreased the latency of the paw-withdrawal and tail-flick responses to heat stimulation [26,27] .…”

“…Furthermore, both electrophysiological and behavior studies indicate that the ACC is involved in nociceptive modulation. Two distinct synaptic circuits in the ACC were found to be activated by noxious stimuli, and two groups of laminar-specific transmembrane sink currents in ACC can be evoked by noxious electrical stimulation: an early group in layers V-VI and a more intense late group in layer II/III and layer V, and lesions in the medial thalamic nucleus blocked these evoked responses in ACC [24] . These results suggest that the medial thalamic nucleus is the major thalamic relay that transmits nociceptive information to the ACC.…”

Cingulate Cortex and Pain Architecture

“…An ACC nociceptive signal arises in the parafascicular thalamic nucleus (Pf) as shown with lidocaine block (Sikes and Vogt, 1992) and ACC is driven by MITN according to lesion (Yang et al, 2006), electrical V. CORTEX stimulation of the thalamus (Hsu and Shyu, 1997;Hsu et al, 2000), and a high correlation between MITN and ACC nociceptive responses (Lee et al, 2007). Nociceptive responses are not limited to ACC as neurons in M2 are driven by noxious cutaneous and colonic stimuli (Sikes and Vogt, 1992;Shih et al, 2008;Wang et al, 2008).…”