Characterization of the glutamatergic system for induction and maintenance of allodynia

Minami, Toshiaki; Matsumura, Shinji; Okuda‐Ashitaka, Emiko; Shimamoto, Keiko; Sakimura, Kenji; Mishina, Masayoshi; Mori, Hidemaro; Ito, Seiji

doi:10.1016/s0006-8993(01)02069-8

Cited by 75 publications

(55 citation statements)

References 42 publications

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“…Intrathecal injection and studies on allodynia were performed as described previously (Minami et al, 2001). Briefly, a 27 gauge stainless steel needle attached to a microsyringe was inserted between the L5 and L6 vertebrae, and drugs in saline (5 l) were injected slowly into the subarachnoid space of conscious mice.…”

Section: Methodsmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide Is Required for the Development of Spinal Sensitization and Induction of Neuropathic Pain

Mabuchi¹,

Shintani²,

Matsumura³

et al. 2004

J. Neurosci.

114

103

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Section: Methodsmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide Is Required for the Development of Spinal Sensitization and Induction of Neuropathic Pain

Mabuchi¹,

Shintani²,

Matsumura³

et al. 2004

J. Neurosci.

114

103

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“…induced bilateral hypernociception was ipsilaterally inhibited by local s.c. injection of morphine or dipyrone. The doses of morphine and dipyrone used had no antinociceptive effect on the contralateral paw hypernociception (8,9). In contrast with inhibitors of prostaglandin synthesis, which prevent the development of nociceptor sensitization, local administration of morphine or dipyrone directly antagonized ongoing hypernociception (10,11).…”

Section: S Timulation Of Postsynaptic N-methyl-d-aspartate (Nmda)mentioning

confidence: 98%

“…Recently, a new spinal mechanism of nociceptor sensitization, retrograde sensitization of the primary sensory neuron, was proposed (8). Induction and maintenance of inflammatory nociceptor sensitization (hypernociception) were shown to depend on spinal cord presynaptic NMDA receptors.…”

Section: S Timulation Of Postsynaptic N-methyl-d-aspartate (Nmda)mentioning

confidence: 99%

Activation of presynaptic NMDA receptors coupled to NaV1.8-resistant sodium channel C-fibers causes retrograde mechanical nociceptor sensitization

Parada

Vivancos

Tambeli

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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. Recently, a new spinal mechanism of nociceptor sensitization, retrograde sensitization of the primary sensory neuron, was proposed (8). Induction and maintenance of inflammatory nociceptor sensitization (hypernociception) were shown to depend on spinal cord presynaptic NMDA receptors. In the present study, we have investigated the importance of sodium tetrodotoxin-resistant (TTX-R Na ϩ ) channels, which are characteristic of peripheral nociceptive small C fibers, for the development of hypernociception induced by intrathecal (i.t.) administration of NMDA.Intrathecal administration of prostaglandin E 2 (PGE 2 ), glutamate, and NMDA causes a bilateral long-lasting mechanical paw hypernociception (up to 6 h; refs. 9 and 10). It was previously shown that i.t. induced bilateral hypernociception was ipsilaterally inhibited by local s.c. injection of morphine or dipyrone. The doses of morphine and dipyrone used had no antinociceptive effect on the contralateral paw hypernociception (8, 9). In contrast with inhibitors of prostaglandin synthesis, which prevent the development of nociceptor sensitization, local administration of morphine or dipyrone directly antagonized ongoing hypernociception (10, 11). Peripheral ipsilateral blockade of mechanical hypernociception induced by i.t.-administered mediators constitutes a simple and straightforward behavioral test to show retrograde sensitization of primary sensory neurons.In the present investigation, mechanical hypernociception was measured with an electronic version of the von Frey hair test, in which the force that evokes a behavioral withdrawal is automatically recorded by an electronic pressure meter. Bilateral paw hypernociception was induced by i.t. administration of NMDA or PGE 2 . Pretreatment of the paws with dipyrone or morphine, at doses shown previously to cause antinociception only in the injected paws, was used to show the sensitization of the primary sensory neurons.Several studies have reported that inflammatory stimuli or mediators can significantly increase TTX-R Na ϩ channel NaV1.8 (SNS͞PN3) mRNA expression and enlarge the amplitude of TTX-R Na ϩ channel currents in dorsal root ganglia (DRG;. TTX-R Na ϩ channels are characteristically associated with fine primary sensory fibers (15, 16). By using antisense oligodeoxynucleotides (ODNs) to selectively ''knock down'' the expression of NaV1.8 (a specific and molecularly distinct TTX-R Na channel), it was shown that NaV1.8 present in primary afferent nociceptors contributes to peripheral sensitization induced by local PGE 2 (15,17). In the present study we reduced the expression of NaV1.8 mRNA by successive i.t. injections of specific antisense ODNs and compared the intensity of paw hypernociception induced by i.t. administration of NMDA with control animals (treated with mismatch ODNs followed by i.t. administration of NMDA). Materials and MethodsAnimals. The experiments were performed on 180-to 200-g male Wistar rats housed in an animal care facility of the University of São Paulo and taken to the testing ...

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“…Responses to the punctate or stroking stimulation of the hindpaw were ranked as follows: 0, no response or moving the stimulated paw aside; 1, lifting of the stimulated paw toward the abdomen; 2, flinching or licking of the stimulated hind paw. In mice given intrathecal injection of strychnine or NMDA, allodynia of the flank was assessed as described (27), with slight modifications. Immediately after intrathecal injection, the mice were individually put in an observation cage (17 × 25 × 12 cm, width × depth × height).…”

Section: Assessment Of Mechanical Allodyniamentioning

confidence: 99%

“…Glycine also acts as co-agonist for NMDA glutamate receptors to facilitate excitatory synaptic transmission (30,31). Since intrathecal injection of either strychnine or NMDA induces dynamic allodynia (27,32), manipulation of synaptic glycine concentrations with GlyT inhibitors may affect dynamic allodynia by influencing both glycinergic inhibitory and glutamatergic excitatory transmission. To address this question, we …”

Section: Effects Of Glyt Inhibitors On Dynamic Allodynia Induced By Smentioning

confidence: 99%

Blockade of Glycine Transporter (GlyT) 2, but Not GlyT1, Ameliorates Dynamic and Static Mechanical Allodynia in Mice With Herpetic or Postherpetic Pain

2010

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Abstract.Glycine is an inhibitory neurotransmitter in the spinal dorsal horn and its extracellular concentration is regulated by glial glycine transporter (GlyT) 1 and neuronal GlyT2. This study was conducted to elucidate the effects of intrathecal injections of GlyT1 and GlyT2 inhibitors on two distinct types of mechanical allodynia, dynamic and static allodynia, in mice with herpetic or postherpetic pain. The GlyT2 inhibitor ALX1393, but not the GlyT1 inhibitor sarcosine, suppressed dynamic and static allodynia at the herpetic and postherpetic stages. Intrathecal ALX1393 suppressed dynamic allodynia induced by intrathecal strychnine and N -methyl-D -aspartate (NMDA). Intrathecal sarcosine suppressed dynamic allodynia induced by intrathecal strychnine, but not NMDA. Expression level of GlyT1, but not GlyT2, mRNA in the lumbar dorsal horn was decreased at the herpetic and postherpetic stages. Glycine receptor α 1-subunit mRNA was decreased in the lumbar dorsal horn at the herpetic, but not postherpetic stage, without alteration in α 3-subunit mRNA. The results suggest that GlyT2 is a potential target for treatment of dynamic and static allodynia in patients with herpes zoster and postherpetic neuralgia. The lack of efficacy of GlyT1 inhibitor may be explained by activation of NMDA receptors and the down-regulation of GlyT1 in the lumbar dorsal horn.

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Characterization of the glutamatergic system for induction and maintenance of allodynia

Cited by 75 publications

References 42 publications

Pituitary Adenylate Cyclase-Activating Polypeptide Is Required for the Development of Spinal Sensitization and Induction of Neuropathic Pain

Pituitary Adenylate Cyclase-Activating Polypeptide Is Required for the Development of Spinal Sensitization and Induction of Neuropathic Pain

Activation of presynaptic NMDA receptors coupled to NaV1.8-resistant sodium channel C-fibers causes retrograde mechanical nociceptor sensitization

Blockade of Glycine Transporter (GlyT) 2, but Not GlyT1, Ameliorates Dynamic and Static Mechanical Allodynia in Mice With Herpetic or Postherpetic Pain

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