Activation of peripheral group III metabotropic glutamate receptors inhibits pain transmission by decreasing neuronal excitability in the CFA-inflamed knee joint

Park, Eui Ho; Lee, Seung Won; Moon, Sangook; Suh, Hye Rim; Kim, Yang In; Han, Hee Chul

doi:10.1016/j.neulet.2018.11.033

Cited by 5 publications

(4 citation statements)

References 26 publications

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“…Activation of Group II mGluRs suppresses prostaglandin E2-induced sensitization of TRPV1 calcium responses in mice [128]. CFA-induced nociceptive behaviors were significantly alleviated by administration of L-AP4, group III mGluR agonist, suggesting that group III mGluRs negatively regulate nociceptive behaviors and pain transmission by lessening neuronal firing rates at the peripheral nerve in inflammation [117]. Group I mGluR antagonists and group II/III mGluR agonists attenuated the enhanced nociception and noxious stimulusinduced glutamate release in the spinal cord dorsal horn in rats of CCI model and injection of CFA into hind paw, suggesting a possible mechanism for their antihyperalgesic effects [129].…”

Section: Glutamate and Painmentioning

confidence: 97%

“…iGluR is a ligand-gated ion channel, whose subtypes are named for the agonist that activates the receptors, including the NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and kainate receptors (KA) [115]. mGluRs contain eight subtypes of receptors and are divided into three groups: Group I mGluRs (mGluR1 and mGluR5) are coupled to phospholipase C, activate PKC, and release Ca 2+ from intracellular stores; Group II mGluRs (mGluR2 and mGluR3) and group III mGluRs (mGluR4, mGluR6-8) inhibit adenylyl cyclase activity [116,117]. Both group II and group III mGluRs are mainly localized on presynaptic terminals.…”

Section: Glutamatementioning

confidence: 99%

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Peripheral Sensitization

Wei¹,

Tao²,

Yang³

et al. 2020

Peripheral Nerve Disorders and Treatment

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Peripheral sensitization indicates increased responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation, which usually occurs after peripheral tissue injury and inflammation. As an integral part of pain, peripheral sensitization and its mechanisms have received much attention, and numerous types of neurotransmitters and chemicals related to peripheral sensitization were investigated. We developed an animal model of peripheral sensitization, and it provides evidence that some neurotransmitters, such as glutamate and substance P, release from adjacent peripheral nerves contributing to the peripheral sensitization of pathological pain. In this chapter, we reviewed the advances in peripheral sensitization, and it will provide a basis for new targets to attenuate pain of peripheral origin.Several animal models of various pain states have been established to investigate the mechanisms of peripheral sensitization, for example, inflammation pain models, neuropathic pain evoked by disease or damage to peripheral nerves, and post-operative pain models. Animal models of inflammatory pain have used a number of different irritants that are injected into skin, paw, muscle, joint, and visceral organ. Carrageenan, complete Freund's adjuvant (CFA), and capsaicin are commonly used inflammatory irritants to induce hyperalgesia. Common nerve injury models include: (1) ligating or transecting the spinal nerves, such as spinal nerve ligation model (SNL); (2) ligating or lesioning the sciatic nerve, such as chronic constriction injury (CCI); and (3) ligating distal branches (peroneal and tibial) of the sciatic nerve (spared nerve injury) [16].To better understand the mechanisms of transmission between peripheral sensory nerve endings, we have successfully established an electrophysiological animal model in which antidromic electrical stimulation of a sensory nerve excites the adjacent primary afferents from the different spinal segments [17]. In this model, two adjacent cutaneous branches of spinal dorsal rami in the thoracic segments, T9 and T10, were dissociated and transected proximally from the spinal cord in anesthetized rats. Then antidromic electrical stimulation with 0.5 ms pulse duration, 20 Hz frequency, and 1 mA intensity was applied to T9 spinal nerve branch, and the nerve activities of T10 nerve branch were recorded [18]. All recorded afferent neurons from the T10 cutaneous branch were classified as Aβ, Aδ, and C fibers according to the conduction velocity and the receptive properties [19]. The discharges of the isolated Aβ, Aδ, and C fibers of the T10 cutaneous branch were significantly enhanced by antidromic electrical stimulation of the adjacent T9 spinal nerve branch [18]. It is in line with our previous studies that antidromic stimulation of T9 spinal nerve branch can activate and sensitize Aβ, Aδ, and C fibers obtained from the adjacent T10 dorsal cutaneous branch [20][21][22][23]. The activation and sensitization of these fibers not only occur between the peripheral sensory nerve...

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Section: Glutamate and Painmentioning

confidence: 97%

Section: Glutamatementioning

confidence: 99%

Peripheral Sensitization

Wei¹,

Tao²,

Yang³

et al. 2020

Peripheral Nerve Disorders and Treatment

View full text Add to dashboard Cite

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“…Little information is available about electrophysiological effects of peripheral group III mGluRs in pain; however, in a recent study, electrophysiological single-unit recordings showed that local administration of a group III mGluR agonist (L-AP4) into the inflamed (CFA) knee joint attenuated neuronal excitability of mechanosensitive C- and Aδ-afferent fibers measured as discharge frequency evoked by the mechanical stimulation of the knee with von Frey filaments. Importantly, the beneficial effects were not observed in the control (sham) group, providing evidence for a pain-specific role of peripheral group III mGluRs [ 173 ]. A group III mGluR antagonist (UBP1112) enhanced the capsaicin-mediated facilitation of single nerve fibers and Ca 2+ mobilization in dissociated DRG neurons without having effects by itself; these responses were abolished by bath application of L-AP4 [ 112 ].…”

Section: Group III Mglurs In Preclinical Pain Modelsmentioning

confidence: 99%

Recent Advances in the Modulation of Pain by the Metabotropic Glutamate Receptors

Mazzitelli

Presto

Antenucci

et al. 2022

Cells

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Metabotropic glutamate receptors (mGluR or mGlu) are G-protein coupled receptors activated by the binding of glutamate, the main classical neurotransmitter of the nervous system. Eight different mGluR subtypes (mGluR1-8) have been cloned and are classified in three groups based on their molecular, pharmacological and signaling properties. mGluRs mediate several physiological functions such as neuronal excitability and synaptic plasticity, but they have also been implicated in numerous pathological conditions including pain. The availability of new and more selective allosteric modulators together with the canonical orthosteric ligands and transgenic technologies has led to significant advances in our knowledge about the role of the specific mGluR subtypes in the pathophysiological mechanisms of various diseases. Although development of successful compounds acting on mGluRs for clinical use has been scarce, the subtype-specific-pharmacological manipulation might be a compelling approach for the treatment of several disorders in humans, including pain; this review aims to summarize and update on preclinical evidence for the roles of different mGluRs in the pain system and discusses knowledge gaps regarding mGluR-related sex differences and neuroimmune signaling in pain.

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“…18) Acher et al, 1997;Tatarczy nska et al, 2002;Pałucha et al, 2004;Kłak et al, 2007;Lopez et al, 2007;Goudet et al, 2008;Pałucha-Poniewiera et al, 2008;Domin et al, 2014, 2016. 19) Fazio et al,2012) Thomsen et al, 1992;Trombley and Westbrook, 1992;Faden et al, 1997;Thomsen, 1997;Pizzi et al, 2000;Naples and Hampson, 2001;Chen and Pan, 2005;Zhou et al, 2006;Lopez et al, 2007;Vernon et al, 2007;Park et al, 2019. 21) Selvam et al, 2007) Nicoletti et al, 1986;Thomsen and Suzdak, 1993;Tizzano et al, 1995;Faden et al, 1997;Tatarczy nska et al, 2001;MacInnes et al, 2004;Antflick et al, 2009.…”

Section: E Orthosteric Ligands In the Clinic: Success And Failurementioning

confidence: 99%