Formalin-induced release of excitatory amino acids in the skin of the rat hindpaw

Omote, Keiichi; Kawamata, Tomoyuki; Kawamata, Mikito; Namiki, Akiyoshi

doi:10.1016/s0006-8993(97)01568-0

Cited by 172 publications

(89 citation statements)

References 21 publications

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“…Activation of NMDA receptors expressed on the peripheral terminals of primary sensory afferents by endogenously released glutamate during injury or inflammation causes pain-related behavior. 61 Peripheral administration of MK801, a noncompetitive NMDA receptor antagonist, produces local anesthetic-like effects and inhibits formalin-induced inflammatory pain. 62 The central sensitization that occurs in the spinal dorsal horn is widely held to be an important event in the pathway leading to neuropathic pain.…”

Section: Function In Chronic Painmentioning

confidence: 99%

Targeting the NMDA Receptor Subunit NR2B for the Treatment of Neuropathic Pain

2009

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Summary:Neuropathic pain is generally defined as a chronic pain state resulting from peripheral or central nerve injury, or both. An effective treatment for neuropathic pain is still lacking. The NMDA receptor, one type of the ionotropic glutamate receptors, is known to be important for triggering long-lasting changes in synapses. NMDA receptor-dependent synaptic plasticity plays roles not only in physiological functions such as learning and memory, but also in unwanted pathological conditions such as chronic pain. This review addresses recent progress on NMDA receptors in neuropathic pain, with particular emphasis on the NR2B-subunitcontaining receptors. The expression and function of NMDA receptors in synaptic plasticity in the pain transmission pathway from dorsal root ganglia to the anterior cingulate cortex is reviewed, and preclinical and clinical investigations of selective NMDA receptor in neuropathic pain are discussed. The NMDA receptors, in particular NR2B-containing NMDA receptors, serve as promising targets for treatment of neuropathic pain.

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Section: Function In Chronic Painmentioning

confidence: 99%

Targeting the NMDA Receptor Subunit NR2B for the Treatment of Neuropathic Pain

2009

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“…It has been demonstrated that Group II activation can inhibit glutamate release in several supraspinal sites (Anwyl, 1999;Cartmell and Schoepp, 2000) and may do so in the periphery as well. When nociceptors are activated, peripheral glutamate is released (Omote et al, 1998;deGroot et al, 2000), thus, intraplantar APDC may attenuate this release, curtailing the subsequent autocrine and/or paracrine activation of excitatory GluRs on nociceptors. This would dampen nociceptor activity and peripheral sensitization (Carlton, 2001).…”

Section: Mechanisms By Which Group II Mglurs Reduce Sensitizationmentioning

confidence: 99%

Group II metabotropic glutamate receptor activation attenuates peripheral sensitization in inflammatory states

Zhou

Carlton

2008

Neuroscience

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Several lines of evidence indicate that Group II metabotropic glutamate receptor (mGluR) activation can depress sensory transmission. We have reported the expression of Group II mGluRs on unmyelinated axons, many of which were presumed to be nociceptors, in the rat digital nerve (Carlton et al., 2001b). The goals of the present study are to further our understanding of Group II modulation of nociceptor processing in the periphery, documenting behavioral changes using inflammatory models and documenting, for the first time, cutaneous single fiber activity following exposure to a Group II agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) and antagonist LY341495 (LY). The data indicate that peripheral Group II mGluR activation does not depress nociceptive behaviors or nociceptor fiber responses in the non-sensitized state (i.e. following brief nociceptive mechanical or thermal stimulation) but can depress these responses when nociceptors are sensitized by exposure to formalin or inflammatory soup. Group II mGluR agonist-induced inhibition can be blocked by a selective Group II antagonist. Peripheral Group II mGluR-induced inhibition evoked in these studies occurs through activation of local receptors and not through spinal or supraspinal mechanisms. The data indicate that administration of selective Group II agonists may be potent therapeutic agents for prevention of peripheral sensitization and for treatment of inflammatory pain. KeywordsGroup II mGluR; pain; APDC; LY341495; formalin; inflammation; inflammatory soup Glutamate and glutamate receptors play an important role in peripheral pain mechanisms in animals (Carlton, 2001;Carlton et al., 2003) and humans (McNearney et al., 1999;McNearney et al., 2000;Cairns et al., 2001;Alfredson et al., 2001;Alfredson and Lorentzon, 2002;Svensson et al., 2003;Cairns et al., 2003). To date, ionotropic glutamate receptors (iGluRs) including N-methyl-D-aspartate (NMDA) and non-NMDA receptors are implicated in peripheral cutaneous pain mechanisms Bleakman et al., 2006).More recent studies indicate that metabotropic glutamate receptors (mGluRs) can modulate peripheral nociceptor function. In contrast to iGluRs, which are ligand-gated ion channel receptors, mGluRs mediate their function via G-protein coupled receptors which trigger Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2009 June 23. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript intracellular second-messenger systems (Pin and Duvoisin, 1995). Accordin...

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“…On the other hand, local administration of antagonists for both ionotropic (Davidson et al, 1997;Davidson and Carlton, 1998) and metabotropic receptors (Bhave et al, 2001;Zhou et al, 2001b) inhibits pain behavior evoked by formalin, as well as hyperalgesia produced by kaolin and carrageenan injected into the knee joint (Lawland et al, 1997). Inflammation of the hindpaw (Omote et al, 1998) or the knee joint produces a local release of glutamate (Lawland et al, 2000) that appears to originate from A and C fibers (deGroot et al, 2000). An additional indirect mechanism, via activation of glutamate receptors on sympathetic afferents to release NA and other substances from postganglionic efferents (e.g., ATP, neuropeptide Y), could occur as NMDA, AMPA, and KA receptors also are present on postganglionic sympathetic efferents, and inflammation enhances the expression of such receptors .…”

Section: F Glutamate Receptor Antagonistsmentioning

confidence: 99%