Interactions Between Glutamate Receptors and TRPV1 Involved in Nociceptive Processing at Peripheral Endings of Primary Afferent Fibers

Jin, Youhong; Takemura, Motohide; Furuyama, Akira; Yonehara, Norifumi

doi:10.5772/34100

Cited by 2 publications

(2 citation statements)

References 50 publications

(61 reference statements)

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“…All three mGluR agonists tested have been shown to modulate neuronal processes through systemic routes of administration The numbers into brackets correspond to the degrees of freedom. ( Linden et al, 2004;Jin et al, 2012;Zhang et al, 2012). On this basis, together with the relative permeability of the blood brain barrier in newborn rodents (Saunders et al, 2012), we then tested the effects of subcutaneous injections of mGluR agonists on the locomotor behavior of P3 and P8-P10 pups by making EMG recordings from the Gastrocnemius and Tibialis Anterior muscles during episodes of spontaneous swimming behavior (see Materials and Methods).…”

Section: Modulation Of the Swimming Behavior By Metabotropic Glutamate Receptor Agonistsmentioning

confidence: 99%

Developmentally Regulated Modulation of Lumbar Motoneurons by Metabotropic Glutamate Receptors: A Cellular and Behavioral Analysis in Newborn Mice

Cazalets

Bertrand

2021

Front. Cell. Neurosci.

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The present study explores the impact of metabotropic glutamate receptor (mGluR) activation on activity-dependent synaptic plasticity (ADSP) and the intrinsic membrane properties of lumbar motoneurons (MNs) using a combination of biochemical, pharmacological, electrophysiological and behavioral techniques. Using spinal cord slices from C57BL/6JRJ mice at two developmental stages, 1-3 and 8-12 postnatal days (P1-P3; P8-P12, respectively), we found that ADSP expressed at glutamatergic synapses between axons conveyed in the ventrolateral funiculus (VLF) and MNs, involved mGluR activation. Using specific agonists of the three groups of mGluRs, we observed that mGluR stimulation causes subtype-specific and developmentally regulated modulation of the ADSP and synaptic transmission at VLF-MN synapses as well as the intrinsic membrane properties of MNs. RT-qPCR analysis revealed a downregulation of mGluR gene expression with age in the ventral part of the lumbar spinal cord. Interestingly, the selective harvest by laser microdissection of MNs innervating the Gastrocnemius and Tibialis anterior muscles unraveled that the level of Grm2 expression is higher in Tibialis MNs compared to Gastrocnemius MNs suggesting a specific mGluR gene expression profile in these two MN pools. Finally, we assessed the functional impact of mGluR modulation on electrically induced bouts of fictive locomotion in the isolated spinal cord preparation of P1-P3 mice, and in vivo during spontaneous episodes of swimming activity in both P1-P3 and P8-P12 mouse pups. We observed that the mGluR agonists induced distinct and specific effects on the motor burst amplitudes and period of the locomotor rhythms tested and that their actions are function of the developmental stage of the animals. Altogether our data show that the metabotropic glutamatergic system exerts a complex neuromodulation in the developing spinal lumbar motor networks and provide new insights into the expression and modulation of ADSP in MNs.

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Section: Modulation Of the Swimming Behavior By Metabotropic Glutamate Receptor Agonistsmentioning

confidence: 99%

Developmentally Regulated Modulation of Lumbar Motoneurons by Metabotropic Glutamate Receptors: A Cellular and Behavioral Analysis in Newborn Mice

Cazalets

Bertrand

2021

Front. Cell. Neurosci.

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“…Given the multiple chemical mediators, including those involved in inflammation and bone degradation (acid), as well as tumour-secreted factors (glutamate), TRPV1 may become sensitized and activated under physiological conditions by its endogenous agonists. Indeed, subcutaneous injection of capsaicin has been shown to induce peripheral glutamate release, which could be inhibited by pre-administration of capsazepine, a TRPV1 antagonist [ 149 , 190 ].…”

Section: Perception Of Extracellular Glutamate In the Periphery: Trpvmentioning

confidence: 99%

Tumour-Derived Glutamate: Linking Aberrant Cancer Cell Metabolism to Peripheral Sensory Pain Pathways

Fazzari¹,

Linher‐Melville

Singh

2017

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BackgroundChronic pain is a major symptom that develops in cancer patients, most commonly emerging during advanced stages of the disease. The nature of cancer-induced pain is complex, and the efficacy of current therapeutic interventions is restricted by the dose-limiting side-effects that accompany common centrally targeted analgesics.MethodsThis review focuses on how up-regulated glutamate production and export by the tumour converge at peripheral afferent nerve terminals to transmit nociceptive signals through the transient receptor cation channel, TRPV1, thereby initiating central sensitization in response to peripheral disease-mediated stimuli.ResultsCancer cells undergo numerous metabolic changes that include increased glutamine catabolism and over-expression of enzymes involved in glutaminolysis, including glutaminase. This mitochondrial enzyme mediates glutaminolysis, producing large pools of intracellular glutamate. Up-regulation of the plasma membrane cystine/glutamate antiporter, system xc-, promotes aberrant glutamate release from cancer cells. Increased levels of extracellular glutamate have been associated with the progression of cancer-induced pain and we discuss how this can be mediated by activation of TRPV1.ConclusionWith a growing population of patients receiving inadequate treatment for intractable pain, new targets need to be considered to better address this largely unmet clinical need for improving their quality of life. A better understanding of the mechanisms that underlie the unique qualities of cancer pain will help to identify novel targets that are able to limit the initiation of pain from a peripheral source–the tumour.

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Interactions Between Glutamate Receptors and TRPV1 Involved in Nociceptive Processing at Peripheral Endings of Primary Afferent Fibers

Cited by 2 publications

References 50 publications

Developmentally Regulated Modulation of Lumbar Motoneurons by Metabotropic Glutamate Receptors: A Cellular and Behavioral Analysis in Newborn Mice

Developmentally Regulated Modulation of Lumbar Motoneurons by Metabotropic Glutamate Receptors: A Cellular and Behavioral Analysis in Newborn Mice

Tumour-Derived Glutamate: Linking Aberrant Cancer Cell Metabolism to Peripheral Sensory Pain Pathways

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