scholarly journals Group II metabotropic glutamate receptor expressing neurons in anterior cingulate cortex become sensitized after inflammatory and neuropathic pain

2020 ◽  
Vol 16 ◽  
pp. 174480692091533
Author(s):  
Sisi Chen ◽  
Feni Kadakia ◽  
Steve Davidson
Keyword(s):  
Neuropathic Pain ◽  
Anterior Cingulate Cortex ◽  
Glutamate Receptor ◽  
Inflammatory Pain ◽  
Metabotropic Glutamate Receptor ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Receptor Subtype ◽  
Metabotropic Glutamate ◽  
Group Ii

The anterior cingulate cortex is a limbic region associated with the emotional processing of pain. How neuropathic and inflammatory pain models alter the neurophysiology of specific subsets of neurons in the anterior cingulate cortex remains incompletely understood. Here, we used a GRM2Cre:tdtomato reporter mouse line to identify a population of pyramidal neurons selectively localized to layer II/III of the murine anterior cingulate cortex. GRM2encodes the group II metabotropic glutamate receptor subtype 2 which possesses analgesic properties in mouse and human models, although its function in the anterior cingulate cortex is not known. The majority of GRM2-tdtomato anterior cingulate cortex neurons expressed GRM2gene product in situ but did not overlap with cortical markers of local inhibitory interneurons, parvalbumin or somatostatin. Physiological properties of GRM2-tdtomato anterior cingulate cortex neurons were investigated using whole-cell patch clamp techniques in slice from animals with neuropathic or inflammatory pain, and controls. After hind-paw injection of Complete Freund’s Adjuvant or chronic constriction injury, GRM2-tdtomato anterior cingulate cortex neurons exhibited enhanced excitability as measured by an increase in the number of evoked action potentials and a decreased rheobase. This hyperexcitability was reversed pharmacologically by bath application of the metabotropic glutamate receptor subtype 2 agonist (2R, 4R)-4-Aminopyrrolidine-2,4-dicarboxylate APDC (1 µM) in both inflammatory and neuropathic models. We conclude that layer II/III pyramidal GRM2-tdtomato anterior cingulate cortex neurons express functional group II metabotropic glutamate receptors and undergo changes to membrane biophysical properties under conditions of inflammatory and neuropathic pain.

Inhibition of Metabotropic Glutamate Receptor Subtype 1 Alters the Excitability of the Commissural Pyramidal Neuron in the Rat Anterior Cingulate Cortex after Chronic Constriction Injury to the Sciatic Nerve

2017 ◽  
Vol 127 (3) ◽  
pp. 515-533 ◽  
Author(s):  
Shi-Hao Gao ◽  
Lin-Lin Shen ◽  
Hui-Zhong Wen ◽  
Yan-Dong Zhao ◽  
Huai-Zhen Ruan
Keyword(s):  
Potassium Channel ◽  
Anterior Cingulate Cortex ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Chronic Constriction Injury ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Receptor Subtype ◽  
Voltage Gated ◽  
Metabotropic Glutamate

Abstract Background Inhibition of the metabotropic glutamate receptor subtype 1 in the anterior cingulate cortex has an analgesic effect during sustained nociceptive hypersensitivity. However, the specific changes in different subtypes of anterior cingulate cortex layer 5 pyramidal neurons, as well as the distinct effect of metabotropic glutamate receptor subtype 1 inhibition on different neuronal subtypes, have not been well studied. Methods Retrograde labeling combined with immunofluorescence, whole cell clamp recording, and behavioral tests combined with RNA interference were performed in a rat model of chronic constriction injury to the sciatic nerve. Results Commissural layer 5 pyramidal neurons (projecting to the contralateral cortex) existed in the anterior cingulate cortex. The voltage-gated potassium channel subunit 2–mediated current in these neurons were substantially reduced after chronic constriction injury (current densities at +30 mV for the sham, and chronic constriction injury neurons were [mean ± SD] 10.22 ± 3.42 pA/pF vs. 5.58 ± 2.71 pA/pF, respectively; n = 11; P < 0.01), which increased the spike width and fast afterhyperpolarization potential, resulting in hyperexcitability. Inhibition of metabotropic glutamate receptor subtype 1 alleviated the down-regulation of voltage-gated potassium channel subunit 2 currents (current density increased by 8.11 ± 3.22 pA/pF; n = 7; P < 0.01). Furthermore, knockdown of voltage-gated potassium channel subunit 2 current in the commissural neurons attenuated the analgesic effect of metabotropic glutamate receptor subtype 1 inhibition (n = 6 rats; P < 0.05). Conclusions The effect of metabotropic glutamate receptor subtype 1 inhibition on commissural anterior cingulate cortex layer 5 pyramidal neurons is likely different with the modification of previously studied hyperpolarization-activated/cyclic nucleotide-gated channel-dependent neurons but relies on the alteration of voltage-gated potassium channel subunit 2 currents. These results will contribute to a better understanding of the therapeutic role of metabotropic glutamate receptor subtype 1 in chronic pain.

The inhibiting role of periaqueductal gray metabotropic glutamate receptor subtype 8 in a rat model of central neuropathic pain

2020 ◽  
Vol 42 (6) ◽  
pp. 515-521 ◽  
Author(s):  
Marjan Hosseini ◽  
Mohsen Parviz ◽  
Alireza P. Shabanzadeh ◽  
Elham Zamani ◽  
Parvaneh Mohseni-Moghaddam ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Glutamate Receptor ◽  
Rat Model ◽  
Metabotropic Glutamate Receptor ◽  
Periaqueductal Gray ◽  
Receptor Subtype ◽  
Central Neuropathic Pain ◽  
Metabotropic Glutamate

scholarly journals Astrocyte activation in the anterior cingulate cortex and altered glutamatergic gene expression during paclitaxel-induced neuropathic pain in mice

PeerJ ◽  
2015 ◽  
Vol 3 ◽  
pp. e1350 ◽  
Author(s):  
Willias Masocha
Keyword(s):  
Gene Expression ◽  
Neuropathic Pain ◽  
Anterior Cingulate Cortex ◽  
Glutamate Receptor ◽  
Pain Perception ◽  
Thermal Hyperalgesia ◽  
Cingulate Cortex ◽  
Glutamate Transporters ◽  
Anterior Cingulate ◽  
Astrocyte Activation

Spinal astrocyte activation contributes to the pathogenesis of paclitaxel-induced neuropathic pain (PINP) in animal models. We examined glial fibrillary acidic protein (GFAP; an astrocyte marker) immunoreactivity and gene expression of GFAP, glutamate transporters and receptor subunits by real time PCR in the anterior cingulate cortex (ACC) at 7 days post first administration of paclitaxel, a time point when mice had developed thermal hyperalgesia. The ACC, an area in the brain involved in pain perception and modulation, was chosen because changes in this area might contribute to the pathophysiology of PINP. GFAP transcripts levels were elevated by more than fivefold and GFAP immunoreactivity increased in the ACC of paclitaxel-treated mice. The 6 glutamate transporters (GLAST, GLT-1 EAAC1, EAAT4, VGLUT-1 and VGLUT-2) quantified were not significantly altered by paclitaxel treatment. Of the 12 ionotropic glutamate receptor subunits transcripts analysed 6 (GLuA1, GLuA3, GLuK2, GLuK3, GLuK5 and GLuN1) were significantly up-regulated, whereas GLuA2, GLuK1, GLuK4, GLuN2A and GLuN2B were not significantly altered and GLuA4 was lowly expressed. Amongst the 8 metabotropic receptor subunits analysed only mGLuR8 was significantly elevated. In conclusion, during PINP there is astrocyte activation, with no change in glutamate transporter expression and differential up-regulation of glutamate receptor subunits in the ACC. Thus, targeting astrocyte activation and the glutamatergic system might be another therapeutic avenue for management of PINP.

scholarly journals Astrocyte activation in the anterior cingulate cortex and altered glutamatergic gene expression during paclitaxel-induced neuropathic pain in mice

2015 ◽  
Author(s):  
Willias Masocha
Keyword(s):  
Gene Expression ◽  
Neuropathic Pain ◽  
Anterior Cingulate Cortex ◽  
Glutamate Receptor ◽  
Pain Perception ◽  
Thermal Hyperalgesia ◽  
Cingulate Cortex ◽  
Glutamate Transporters ◽  
Anterior Cingulate ◽  
Astrocyte Activation

Spinal astrocyte activation contributes to the pathogenesis of paclitaxel-induced neuropathic pain (PINP) in animal models. We examined gene expression of glial fibrillary acidic protein (GFAP; an astrocyte marker), glutamate transporters and receptor subunits in the anterior cingulate cortex (ACC) by real time PCR at 7 days post first administration of paclitaxel, a time point when mice had developed thermal hyperalgesia. Changes in the ACC, an area in the brain involved in pain perception and modulation, might contribute to the pathophysiology of PINP. GFAP transcripts levels were elevated by more than fivefold in the ACC of paclitaxel-treated mice. The 6 glutamate transporters (GLAST, GLT-1 EAAC1, EAAT4, VGLUT-1 and VGLUT-2) quantified were not significantly altered by paclitaxel treatment. Of the 12 ionotropic glutamate receptor subunits transcripts analysed 6 (GLuA1, GLuA3, GLuK2, GLuK3, GLuK5 and GLuN1) were significantly up-regulated, whereas GLuA2, GLuK1, GLuK4, GLuN2A and GLuN2B were not significantly altered and GLuA4 was lowly expressed. Amongst the 8 metabotropic receptor subunits analysed only mGLuR 8 was significantly elevated. In conclusion, during PINP there is astrocyte activation, no change in glutamate transporter expression and differential up-regulation of glutamate receptor subunits in the ACC. Thus, targeting astrocyte activation and the glutamatergic system might be another therapeutic avenue for management of PINP.

scholarly journals Astrocyte activation in the anterior cingulate cortex and altered glutamatergic gene expression during paclitaxel-induced neuropathic pain in mice

2015 ◽  
Author(s):  
Willias Masocha
Keyword(s):  
Gene Expression ◽  
Neuropathic Pain ◽  
Anterior Cingulate Cortex ◽  
Glutamate Receptor ◽  
Pain Perception ◽  
Thermal Hyperalgesia ◽  
Cingulate Cortex ◽  
Glutamate Transporters ◽  
Anterior Cingulate ◽  
Astrocyte Activation

Spinal astrocyte activation contributes to the pathogenesis of paclitaxel-induced neuropathic pain (PINP) in animal models. We examined glial fibrillary acidic protein (GFAP; an astrocyte marker) immunoreactivity and gene expression of GFAP, glutamate transporters and receptor subunits by real time PCR in the anterior cingulate cortex (ACC) at 7 days post first administration of paclitaxel, a time point when mice had developed thermal hyperalgesia. The ACC, an area in the brain involved in pain perception and modulation, was chosen because changes in this area might contribute to the pathophysiology of PINP. GFAP transcripts levels were elevated by more than fivefold and GFAP immunoreactivity increased in the ACC of paclitaxel-treated mice. The 6 glutamate transporters (GLAST, GLT-1 EAAC1, EAAT4, VGLUT-1 and VGLUT-2) quantified were not significantly altered by paclitaxel treatment. Of the 12 ionotropic glutamate receptor subunits transcripts analysed 6 (GLuA1, GLuA3, GLuK2, GLuK3, GLuK5 and GLuN1) were significantly up-regulated, whereas GLuA2, GLuK1, GLuK4, GLuN2A and GLuN2B were not significantly altered and GLuA4 was lowly expressed. Amongst the 8 metabotropic receptor subunits analysed only mGLuR8 was significantly elevated. In conclusion, during PINP there is astrocyte activation, no change in glutamate transporter expression and differential up-regulation of glutamate receptor subunits in the ACC. Thus, targeting astrocyte activation and the glutamatergic system might be another therapeutic avenue for management of PINP.

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