Evidence that DHPG-induced nociception depends on glutamate release from primary afferent C-fibres

Lefebvre, Celeste D.; Fisher, Kim; Cahill, Catherine M.; Coderre, Terence J.

doi:10.1097/00001756-200006050-00007

Cited by 23 publications

(9 citation statements)

References 22 publications

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“…Also in sheep, intrathecal administration of low doses of 3,5-DHPG increases the responsiveness to noxious mechanical stimulation (mechanical hyperalgesia), an effect that is reversed by the coadministration of AIDA (Dolan and Nolan, 2000). The induction of spon-MGLU1 STRUCTURE AND FUNCTION taneous nociceptive behaviors by 3,5-DHPG seems to depend on glutamate release from primary afferent Cfibers (Lefebvre et al, 2000;Lorrain et al, 2002). In monkeys, capsaicin injection or 3,5-DHPG administration by microdialysis produces central sensitization of spinothalamic tract cells and enhances responses to both innocuous and noxious stimuli (Neugebauer et al, 1999).…”

Section: G Painmentioning

confidence: 96%

Metabotropic Glutamate 1 Receptor: Current Concepts and Perspectives

Ferraguti

Crepaldi

Nicoletti³

2008

Pharmacol Rev

193

205

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Almost 25 years after the first report that glutamate can activate receptors coupled to heterotrimeric G-proteins, tremendous progress has been made in the field of metabotropic glutamate receptors. Now, eight members of this family of glutamate receptors, encoded by eight different genes that share distinctive structural features have been identified. The first cloned receptor, the metabotropic glutamate ( mGlu) receptor mGlu1 has probably been the most extensively studied mGlu receptor, and in many respects it represents a prototypical subtype for this family of receptors. Its biochemical, anatomical, physiological, and pharmacological characteristics have been intensely investigated. Together with subtype 5, mGlu1 receptors constitute a subgroup of receptors that couple to phospholipase C and mobilize Ca(2+) from intracellular stores. Several alternatively spliced variants of mGlu1 receptors, which differ primarily in the length of their C-terminal domain and anatomical localization, have been reported. Use of a number of genetic approaches and the recent development of selective antagonists have provided a means for clarifying the role played by this receptor in a number of neuronal systems. In this article we discuss recent advancements in the pharmacology and concepts about the intracellular transduction and pathophysiological role of mGlu1 receptors and review earlier data in view of these novel findings. The impact that this new and better understanding of the specific role of these receptors may have on novel treatment strategies for a variety of neurological and psychiatric disorders is considered

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Section: G Painmentioning

confidence: 96%

Metabotropic Glutamate 1 Receptor: Current Concepts and Perspectives

Ferraguti

Crepaldi

Nicoletti³

2008

Pharmacol Rev

193

205

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“…In addition to the critical role of NMDAR in increasing the excitability nociceptive neurons, activation of group I mGluRs by glutamate also appear important for the development of central sensitization. Although these receptors do not participate to basal nociception,221,392 their activation is necessary for activity-dependent central sensitization mediated by C-fibers 14,67,165,296,392,393. In contrast, activation of group II-III mGluRs is associated with a reduction of capsaicin-induced central sensitization 296…”

Section: Triggers Of Activity-dependent Central Sensitizationmentioning

confidence: 99%

Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity

Latrémolière

Woolf

2009

The Journal of Pain

2,901

2,457

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Central sensitization represents an enhancement in the function of neurons and circuits in nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as well as to reduced inhibition and is a manifestation of the remarkable plasticity of the somatosensory nervous system in response to activity, inflammation, and neural injury. The net effect of central sensitization is to recruit previously subthreshold synaptic inputs to nociceptive neurons, generating an increased or augmented action potential output: a state of facilitation, potentiation, augmentation, or amplification. Central sensitization is responsible for many of the temporal, spatial, and threshold changes in pain sensibility in acute and chronic clinical pain settings and exemplifies the fundamental contribution of the central nervous system to the generation of pain hypersensitivity. Because central sensitization results from changes in the properties of neurons in the central nervous system, the pain is no longer coupled, as acute nociceptive pain is, to the presence, intensity, or duration of noxious peripheral stimuli. Instead, central sensitization produces pain hypersensitivity by changing the sensory response elicited by normal inputs, including those that usually evoke innocuous sensations.Perspective-In this article, we review the major triggers that initiate and maintain central sensitization in healthy individuals in response to nociceptor input and in patients with inflammatory and neuropathic pain, emphasizing the fundamental contribution and multiple mechanisms of synaptic plasticity caused by changes in the density, nature, and properties of ionotropic and metabotropic glutamate receptors. KeywordsCentral sensitization; inflammatory pain; neuropathic pain; scaffolding protein; heterosynaptic facilitation Acute nociceptive pain is that physiological sensation of hurt that results from the activation of nociceptive pathways by peripheral stimuli of sufficient intensity to lead to or to threaten tissue damage (noxious stimuli). 374 Nociception, the detection of noxious stimuli, 282 is a protective process that helps prevent injury by generating both a reflex withdrawal from the stimulus and as a sensation so unpleasant that it results in complex behavioral strategies to avoid further contact with such stimuli. An additional important phenomenon that further enhances this protective function is the sensitization of the nociceptive system that occurs after repeated or particularly intense noxious stimuli, so that the threshold for its activation falls and responses to subsequent inputs are amplified. 132,376,380 In the absence of ongoing tissue injury, NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript this state of heightened sensitivity returns over time to the normal baseline, where highintensity stimuli are again required to initiate nociceptive pain; the phenomenon is long lasting but not permanent. The nociceptor-induced sensitization of the somatosensory system is adaptive in...

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“…At the spinal cord level, activation of group I mGlu receptors has been proposed to favor glutamate release, then contributing to nociceptive plasticity and excitotoxic events that follow spinal cord injury (Lefebvre et al, 2000; Mills et al, 2001; Lorrain et al, 2002). The mGlu5 receptor subtype was proposed to play the major role in these events (Hu et al, 2007; Hu and Gereau, 2011), but the participation of mGlu1 receptor subtypes was not excluded (Mills et al, 2001).…”

Section: Mglu1 Autoreceptors In Central Nervous Systemmentioning

confidence: 99%

Presynaptic Release-Regulating mGlu1 Receptors in Central Nervous System

Pittaluga

2016

Front. Pharmacol.

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Group I metabotropic glutamate (mGlu) receptors consists of mGlu1 and mGlu5 receptor subtypes. These receptors are widely distributed in the central nervous system (CNS), where they preferentially mediate facilitatory signaling in neurones and glial cells, mainly by favoring phospholipase (PLC) translocation. Based on the literature so far available, group I Metabotropic glutamate receptors (mGluRs) are preferentially expressed at the postsynaptic side of chemical synapsis, where they participate in the progression of the chemical stimulus. Studies, however, have shown the presence of these receptors also at the presynaptic level, where they exert several functions, including the modulation of transmitter exocytosis. Presynaptic Group I mGluRs can be both autoreceptors regulating release of glutamate and heteroreceptors regulating the release of various transmitters, including GABA, dopamine, noradrenaline, and acetylcholine. While the existence of presynaptic release-regulating mGlu5 receptors is largely recognized, the possibility that mGlu1 receptors also are present at this level has been a matter of discussion for a long time. A large body of evidence published in the last decade, however, supports this notion. This review aims at revisiting the data from in vitro studies concerning the existence and the role of release-regulating mGlu1 receptors presynaptically located in nerve terminals isolated from selected regions of the CNS. The functional interaction linking mGlu5 and mGlu1 receptor subtypes at nerve terminals and their relative contributions as modulators of central transmission will also be discussed. We apologize in advance for omission in our coverage of the existing literature.

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Evidence that DHPG-induced nociception depends on glutamate release from primary afferent C-fibres

Cited by 23 publications

References 22 publications

Metabotropic Glutamate 1 Receptor: Current Concepts and Perspectives

Metabotropic Glutamate 1 Receptor: Current Concepts and Perspectives

Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity

Presynaptic Release-Regulating mGlu1 Receptors in Central Nervous System

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