Kainate Receptors and Pain: From Dorsal Root Ganglion to the Anterior Cingulate Cortex

Wu, Long Jun; Ko, Shanelle W.; Zhuo, Min

doi:10.2174/138161207780765864

Cited by 40 publications

(25 citation statements)

References 95 publications

(118 reference statements)

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“…In our study, the percentage of KA-responsive DRG neurons is consistent with previous patch clamp studies on dissociated neurons [34]. Compared to other ionotropic GluRs, the importance of KA receptors in nociception has only recently been recognized [35]. Electrophysiological evidence shows that in DRGs, KA receptors are found mainly on small and medium neurons [36].…”

Section: Discussionsupporting

confidence: 91%

Increased Response to Glutamate in Small Diameter Dorsal Root Ganglion Neurons after Sciatic Nerve Injury

et al. 2014

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Glutamate in the peripheral nervous system is involved in neuropathic pain, yet we know little how nerve injury alters responses to this neurotransmitter in primary sensory neurons. We recorded neuronal responses from the ex-vivo preparations of the dorsal root ganglia (DRG) one week following a chronic constriction injury (CCI) of the sciatic nerve in adult rats. We found that small diameter DRG neurons (<30 µm) exhibited increased excitability that was associated with decreased membrane threshold and rheobase, whereas responses in large diameter neurons (>30 µm) were unaffected. Puff application of either glutamate, or the selective ionotropic glutamate receptor agonists alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid (KA), or the group I metabotropic receptor (mGluR) agonist (S)-3,5-dihydroxyphenylglycine (DHPG), induced larger inward currents in CCI DRGs compared to those from uninjured rats. N-methyl-D-aspartate (NMDA)-induced currents were unchanged. In addition to larger inward currents following CCI, a greater number of neurons responded to glutamate, AMPA, NMDA, and DHPG, but not to KA. Western blot analysis of the DRGs revealed that CCI resulted in a 35% increase in GluA1 and a 60% decrease in GluA2, the AMPA receptor subunits, compared to uninjured controls. mGluR1 receptor expression increased by 60% in the membrane fraction, whereas mGluR5 receptor subunit expression remained unchanged after CCI. These results show that following nerve injury, small diameter DRG neurons, many of which are nociceptive, have increased excitability and an increased response to glutamate that is associated with changes in receptor expression at the neuronal membrane. Our findings provide further evidence that glutamatergic transmission in the periphery plays a role in nociception.

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Section: Discussionsupporting

confidence: 91%

Increased Response to Glutamate in Small Diameter Dorsal Root Ganglion Neurons after Sciatic Nerve Injury

et al. 2014

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“…Genetic deletion of the GluR6 or GluR5 subunit significantly reduced, and GluR5 and 6 double knockout completely abolished, KA EPSCs and KA-activated currents in ACC pyramidal neurons [42]. We believe that KA receptors in the ACC may also contribute to pain and its related emotion such as anxiety [44,45]. …”

Section: Excitatory Synaptic Transmission and Plasticity In The Accmentioning

confidence: 99%

Neuronal Mechanism for Neuropathic Pain

2007

Self Cite

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Among different forms of persistent pain, neuropathic pain presents as a most difficult task for basic researchers and clinicians. Despite recent rapid development of neuroscience and modern techniques related to drug discovery, effective drugs based on clear basic mechanisms are still lacking. Here, I will review the basic neuronal mechanisms that maybe involved in neuropathic pain. I will present the problem of neuropathic pain as a rather difficult task for neuroscientists, and we may have to wait for a long time before we fully understand how brain encode, store, and retrieve painful information after the injury. I propose that neuropathic pain as a major brain disease, rather being a clinic problem due to peripheral injury.

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“…Nearly a third of the world population experiences clinical pathological pain [3]. Pain is believed to be caused by aberrant neuronal responses along the pain transmission pathway from the dorsal root ganglion (DRG) to the spinal cord, thalamus, and cortex [4]. Accumulating evidence indicates that neuroinflammation may play a vital role in the pain transmission pathway.…”

Section: Introductionmentioning

confidence: 99%

Paeoniflorin Attenuates Inflammatory Pain by Inhibiting Microglial Activation and Akt-NF-κB Signaling in the Central Nervous System

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Paeoniflorin (PF) is known to have anti-inflammatory and paregoric effects, but the mechanism underlying its analgesic effect remains unclear. The aim of this study was to clarify the effect of PF on Freund’s complete adjuvant (CFA)-induced inflammatory pain and explore the underlying molecular mechanism. Methods: An inflammatory pain model was established by intraplantar injection of CFA in C57BL/6J mice. After intrathecal injection of PF daily for 8 consecutive days, thermal and mechanical withdrawal thresholds, the levels of inflammatory factors TNF-α, IL-1β and IL-6, microglial activity, and the expression of Akt-NF-κB signaling pathway in the spinal cord tissue were detected by animal ethological test, cell culture, enzyme-linked immunosorbent assay, immunofluorescence histochemistry, and western blot. Results: PF inhibited the spinal microglial activation in the CFA-induced pain model. The production of proinflammatory cytokines was decreased in the central nervous system after PF treatment both in vivo and in vitro. PF further displayed a remarkable effect on inhibiting the activation of Akt-NF-κB signaling pathway in vivo and in vitro. Conclusion: These results suggest that PF is a potential therapeutic agent for inflammatory pain and merits further investigation.

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Kainate Receptors and Pain: From Dorsal Root Ganglion to the Anterior Cingulate Cortex

Cited by 40 publications

References 95 publications

Increased Response to Glutamate in Small Diameter Dorsal Root Ganglion Neurons after Sciatic Nerve Injury

Increased Response to Glutamate in Small Diameter Dorsal Root Ganglion Neurons after Sciatic Nerve Injury

Neuronal Mechanism for Neuropathic Pain

Paeoniflorin Attenuates Inflammatory Pain by Inhibiting Microglial Activation and Akt-NF-κB Signaling in the Central Nervous System

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