NMDA Receptors and Signaling in Chronic Neuropathic Pain

Laumet, Geoffroy; Pan, Hui Lin

doi:10.1007/978-3-319-49795-2_6

Cited by 6 publications

(4 citation statements)

References 116 publications

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“…Depolarization of neurons cause Mg 2+ ions unblocked from NMDAR which facilitates ion influx. 5 NMDAR's activation activates downstream cascade reactions such as increased intracellular calcium influx which acts as a secondary messenger in mitogen-activated protein kinases (MAP kinase), one of the pain pathways. MAP activation resulting in the elevation of the phosphorylated extracellular signalregulated kinase (pERK) which increases the translation of NMDAR and AMPAR and their expression in the cell membrane, leading to central sensitization.…”

Section: Central Sensitization and Painmentioning

confidence: 99%

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Pulsed Radiofrequency Decreases pERK and Affects Intracellular Ca2+ Influx, Cytosolic ATP Level, and Mitochondrial Membrane Potential in the Sensitized Dorsal Root Ganglion Neuron Induced by N-Methyl D-Aspartate

Laksono¹,

Kalim²,

Rohman³

et al. 2023

JPR

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Background:The molecular mechanism of pulsed radiofrequency (PRF) in chronic pain management is not fully understood. Chronic pain involves the activation of specific N-Methyl D-Aspartate receptors (NMDAR) to induce central sensitization. This study aims to determine the effect of PRF on central sensitization biomarker phosphorylated extracellular signal-regulated kinase (pERK), Ca 2+ influx, cytosolic ATP level, and mitochondrial membrane potential (Δψm) of the sensitized dorsal root ganglion (DRG) neuron following NMDAR activation. Methods: This study is a true experimental in-vitro study on a sensitized DRG neuron induced with 80 µM NMDA. There are six treatment groups including control, NMDA 80 µM, Ketamine 100 µM, PRF 2Hz, NMDA 80 µM + PRF 2 Hz, and NMDA 80 µM + PRF 2 Hz + ketamine 100 µM. We use PRF 2 Hz 20 ms for 360 seconds. Statistical analysis was performed using the One-Way ANOVA and the Pearson correlation test with α=5%. Results: In the sensitized DRG neuron, there is a significant elevation of pERK. There is a strong correlation between Ca 2+ , cytosolic ATP level, and Δψm with pERK intensity (p<0.05). PRF treatment decreases pERK intensity from 108. 48 ± 16.95 AU to 38.57 ± 5.20 AU (p<0.05). PRF exposure to sensitized neurons also exhibits a Ca 2+ influx, but still lower than in the unexposed neuron. PRF exposure in sensitized neurons has a higher cytosolic ATP level (0.0458 ± 0.0010 mM) than in the unexposed sensitized neuron (0.0198 ± 0.0004 mM) (p<0.05). PRF also decreases Δψm in the sensitized neuron from 109.24 ± 6.43 AU to 33.21 ± 1.769 AU (p<0.05). Conclusion: PRF mechanisms related to DRG neuron sensitization are by decreasing pERK, altering Ca 2+ influx, increasing cytosolic ATP level, and decreasing Δψm which is associated with neuron sensitization following NMDAR activation.

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Section: Central Sensitization and Painmentioning

confidence: 99%

“…1,2 The prevalence of chronic pain conditions was 37.3% in developed countries and 41.1% in developing countries. 3 Chronic pain is associated with the activation of the N-methyl-D-aspartate receptor (NMDAR), one of the glutamate receptors, 4 which also plays a role in synaptic plasticity, 5…”

Section: Introductionmentioning

confidence: 99%

Pulsed Radiofrequency Decreases pERK and Affects Intracellular Ca2+ Influx, Cytosolic ATP Level, and Mitochondrial Membrane Potential in the Sensitized Dorsal Root Ganglion Neuron Induced by N-Methyl D-Aspartate

Laksono¹,

Kalim²,

Rohman³

et al. 2023

JPR

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“…19 The NMDA receptors are abundantly distributed in the pain pathway and are responsible for synaptic plasticity corresponding to chronic pain. 20 Painful stimuli cause the activation of afferent myelinated A δ and unmyelinated C fibers that cause a release of glutamate along with substance P and neurokinin A in the dorsal horn of the spinal cord. This makes the postsynaptic neurons fire that project signal to the supraspinal structures of the CNS.…”

Section: Nmda Receptors System: a Key Player In The Pathophysiology O...mentioning

confidence: 99%

“…NMDA receptors have been widely implicated in the transmission of both nociceptive and neuropathic pain . The NMDA receptors are abundantly distributed in the pain pathway and are responsible for synaptic plasticity corresponding to chronic pain . Painful stimuli cause the activation of afferent myelinated A δ and unmyelinated C fibers that cause a release of glutamate along with substance P and neurokinin A in the dorsal horn of the spinal cord.…”

Section: Nmda Receptors System: a Key Player In The Pathophysiology O...mentioning

confidence: 99%

Kinesin Nanomotors Mediated Trafficking of NMDA-Loaded Cargo as A Novel Target in Chronic Pain

Uniyal

Thakur

Rani

et al. 2021

ACS Chem. Neurosci.

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Chronic pain is among the most prevalent burdensome disorders worldwide. The N-methyl-d-aspartate (NMDA) receptor system plays a critical role in central sensitization, a primary feature of chronic pain. Despite the proven efficacy of exogenous ligands to this receptor system in preclinical studies, evidence for the clinical efficacy of NMDA antagonists for the treatment of chronic pain is weak. Researchers are studying alternate approaches, rather than direct inhibition of the NMDA receptors in pain processing neurons. This indirect approach utilizes the modulation of molecular switches that regulates the synthesis, maturation, and transport of receptors from cellular organelles to the synaptic membrane. Kinesins are nanomotors that anterogradely transport the cargo using microtubule tracks across the neurons. Various members of the kinesin family, including KIF17, KIF11, KIF5b, and KIF21a, regulate the intracellular transport of NMDA receptors. Pharmacological targeting of these ATP-driven nanomotors could be a useful tool for manipulating the NMDAR functioning. It could provide the potential for the development of a novel strategy for the management of chronic pain.

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Can FDA-Approved Immunomodulatory Drugs be Repurposed/Repositioned to Alleviate Chronic Pain?

Inyang

Folger

Laumet

2021

J Neuroimmune Pharmacol

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NMDA Receptors and Signaling in Chronic Neuropathic Pain

Cited by 6 publications

References 116 publications

Pulsed Radiofrequency Decreases pERK and Affects Intracellular Ca2+ Influx, Cytosolic ATP Level, and Mitochondrial Membrane Potential in the Sensitized Dorsal Root Ganglion Neuron Induced by N-Methyl D-Aspartate

Pulsed Radiofrequency Decreases pERK and Affects Intracellular Ca2+ Influx, Cytosolic ATP Level, and Mitochondrial Membrane Potential in the Sensitized Dorsal Root Ganglion Neuron Induced by N-Methyl D-Aspartate

Kinesin Nanomotors Mediated Trafficking of NMDA-Loaded Cargo as A Novel Target in Chronic Pain

Can FDA-Approved Immunomodulatory Drugs be Repurposed/Repositioned to Alleviate Chronic Pain?

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