Persistent Activity of Metabotropic Glutamate Receptor 5 in the Periaqueductal Gray Constrains Emergence of Chronic Neuropathic Pain

Chung, Geehoon; Shim, Hyun Geun; Kim, Chae Young; Ryu, Hwa-Sung; Jang, Dong Cheol; Kim, Seung Ha; Lee, Jaegeon; Kim, Chang Eop; Kim, Yu Kyeong; Lee, Yong Seok; Kim, Jun; Kim, Sun Kwang; Worley, Paul F.; Kim, Sang Jeong

doi:10.1016/j.cub.2020.09.008

Cited by 9 publications

(11 citation statements)

References 51 publications

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“…We further investigated whether MTEP microinjection into the S1DZ affected spontaneous ongoing pain in the SNL group. The CPP test, an analysis that can be used to measure the effectiveness of the intervention on tonic-aversive pain perception, was performed according to previous studies [ 22 , 24 , 29 , 32 ]. Before the conditioning process, animals in both groups showed no preference for either chamber ( Figure 4 A,D).…”

Section: Resultsmentioning

confidence: 99%

“…Injection of various mGluR5 antagonists induced analgesic effects in neuropathic pain animals [ 20 , 40 ]. In the brain, mGluR5 in the cortical regions mainly promotes pain perception [ 23 , 39 ], whereas mGluR5 in the pain modulatory area, such as periaqueductal gray, inhibits pain [ 22 , 41 , 42 ]. The potent anti-allodynic effect induced by microinjection of MTEP into the S1DZ in the current study indicates that mGluR5 in this region is critically involved in the distorted sensory-discriminative function.…”

Section: Discussionmentioning

confidence: 99%

“…Metabotropic glutamate receptor 5 (mGluR5) is a key mediator of neural plasticity and plays a critical role in changes in the nervous system in various neurological disorders. mGluR5 is highly expressed across the nervous system, including in pain circuits, and is involved in the mechanisms of neuropathic pain [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. In a previous study, we measured mGluR5 availability in the whole rat brain using a positron emission tomography (PET) imaging with an mGluR5-specific radiotracer, [ 11 C] ABP688.…”

Section: Introductionmentioning

confidence: 99%

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Metabotropic Glutamate Receptor 5 in the Dysgranular Zone of Primary Somatosensory Cortex Mediates Neuropathic Pain in Rats

et al. 2022

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The primary somatosensory cortex (S1) plays a key role in the discrimination of somatic sensations. Among subdivisions in S1, the dysgranular zone of rodent S1 (S1DZ) is homologous to Brodmann’s area 3a of primate S1, which is involved in the processing of noxious signals from the body. However, molecular changes in this region and their role in the pathological pain state have never been studied. In this study, we identified molecular alteration of the S1DZ in a rat model of neuropathic pain induced by right L5 spinal nerve ligation (SNL) surgery and investigated its functional role in pain symptoms. Brain images acquired from SNL group and control group in our previous study were analyzed, and behaviors were measured using the von Frey test, acetone test, and conditioned place preference test. We found that metabotropic glutamate receptor 5 (mGluR5) levels were significantly upregulated in the S1DZ contralateral to the nerve injury in the SNL group compared to the sham group. Pharmacological deactivation of mGluR5 in S1DZ ameliorated symptoms of neuropathic allodynia, which was shown by a significant increase in the mechanical paw withdrawal threshold and a decrease in the behavioral response to cold stimuli. We further confirmed that this treatment induced relief from the tonic-aversive state of chronic neuropathic pain, as a place preference memory associated with the treatment-paired chamber was formed in rats with neuropathic pain. Our data provide evidence that mGluR5 in the S1DZ is involved in the manifestation of abnormal pain sensations in the neuropathic pain state.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metabotropic Glutamate Receptor 5 in the Dysgranular Zone of Primary Somatosensory Cortex Mediates Neuropathic Pain in Rats

et al. 2022

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“…PAG-RVM-projecting neurons showed a reduction in excitatory input, as demonstrated by electrophysiological recordings of retrogradely labeled neurons. Interestingly, a single injection of mGluR5 inverse agonist 2-methyl-6-(phenylethynyl) pyridine (MPEP) or mGluR1 inverse agonist BAY 36-7620 in naïve animals resulted in mechanical allodynia and decreased the intrinsic excitability of ventrolateral PAG (vlPAG) neurons [91].…”

Section: Plasticity In Glutamatergic Pathway In the Pag During Neuropathic Painmentioning

confidence: 99%

“…Notably, this modulation of Homer1a specifically affects the late phase of neuropathic pain, and this analgesic effect lasts for a long time. They also showed that administration of 3,5-dihydroxyphenylglycine (DHPG), the mGluR1/5 agonist, into the PAG leads to an analgesic effect on SNL-induced mechanical allodynia [91].…”

Section: Plasticity In Glutamatergic Pathway In the Pag During Neuropathic Painmentioning

confidence: 99%

Neural Plasticity in the Brain during Neuropathic Pain

2021

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Neuropathic pain is an intractable chronic pain, caused by damage to the somatosensory nervous system. To date, treatment for neuropathic pain has limited effects. For the development of efficient therapeutic methods, it is essential to fully understand the pathological mechanisms of neuropathic pain. Besides abnormal sensitization in the periphery and spinal cord, accumulating evidence suggests that neural plasticity in the brain is also critical for the development and maintenance of this pain. Recent technological advances in the measurement and manipulation of neuronal activity allow us to understand maladaptive plastic changes in the brain during neuropathic pain more precisely and modulate brain activity to reverse pain states at the preclinical and clinical levels. In this review paper, we discuss the current understanding of pathological neural plasticity in the four pain-related brain areas: the primary somatosensory cortex, the anterior cingulate cortex, the periaqueductal gray, and the basal ganglia. We also discuss potential treatments for neuropathic pain based on the modulation of neural plasticity in these brain areas.

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Disruption of Periaqueductal Gray-default Mode Network Functional Connectivity in Patients with Crohn's Disease with Abdominal Pain

Zhang

Chen

et al. 2023

Neuroscience

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Persistent Activity of Metabotropic Glutamate Receptor 5 in the Periaqueductal Gray Constrains Emergence of Chronic Neuropathic Pain

Cited by 9 publications

References 51 publications

Metabotropic Glutamate Receptor 5 in the Dysgranular Zone of Primary Somatosensory Cortex Mediates Neuropathic Pain in Rats

Metabotropic Glutamate Receptor 5 in the Dysgranular Zone of Primary Somatosensory Cortex Mediates Neuropathic Pain in Rats

Neural Plasticity in the Brain during Neuropathic Pain

Disruption of Periaqueductal Gray-default Mode Network Functional Connectivity in Patients with Crohn's Disease with Abdominal Pain

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