Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in glycinergic neurotransmission in the spinal cord dorsal horn are critically involved in the development of pathological pain. Since the concentration of glycine in the synaptic cleft is controlled by specialized proteins, the glycine transporters GlyT1 and GlyT2, manipulation of this system might have significant effects on nociception. In the present study, we investigated the effects of the spinally applied glycine transporter inhibitors ALX 5407 (GlyT1) and ALX 1393 (GlyT2) on nociceptive behavior in the chronic constriction injury model of neuropathic pain in male Wistar rats. After implementation of neuropathy, the animals were injected with three dosages of ALX 5407 and ALX 1393 (10, 50 and 100 microg) via an intrathecal catheter (n = 8 each). Subsequently, nociceptive behavior was evaluated regarding thermal hyperalgesia (Hargreaves method) and mechanical sensitization (von Frey filaments) over 240 min after application. Inhibition of GlyT1 by ALX 5407 had differential dose-dependent effects. While the highest and the lowest concentrations were antinociceptive, the medium dose evoked pronociceptive effects. The GlyT2 inhibitor ALX 1393 was only effective in the highest concentration at which it exerted significant antinociception. However, in the same dose, ALX 1393 caused remarkable side effects such as respiratory depression and motor deficits in three animals. Our findings indicate that inhibition of glycine transporters is capable of evoking significant effects on nociceptive behavior in neuropathic pain. Whether glycine transporter inhibitors have the capability to gain clinical relevance as analgesic compounds on the long run has to be elucidated in further investigations.
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PMID:Differential effects of spinally applied glycine transporter inhibitors on nociception in a rat model of neuropathic pain. 1879 97

Glycinergic inhibitory neurotransmission plays a pivotal role in the development of neuropathic pain. The glycine concentration in the synaptic cleft is controlled by the glycine transporters GlyT1 and GlyT2. GlyT1 is expressed throughout the central nervous system, while GlyT2 is exclusively located in glycinergic neurons. Aim of the present study was to investigate whether GlyTs are also expressed in the peripheral sensory nervous system and whether their expression is modulated in experimental neuropathic pain. Neuropathic pain was induced in male Wistar rats by Chronic Constriction Injury (CCI) and verified by assessment of mechanical allodynia (von Frey method). Expression patterns of GlyTs and the glycine binding subunit NR1 of the N-methyl-d-aspartate (NMDA) receptor in the spinal cord and dorsal root ganglia (DRG) were analyzed by Western blot analysis, PCR and immunohistochemistry. While both GlyT1 and GlyT2 were detected in the spinal cord, only GlyT1, but not GlyT2, was detected in DRG. Immunofluorescence revealed a strictly neuronal localization of GlyT1 and a co-localization of GlyT1 and NR1 in DRG. Compared to sham procedure, spinal cord and DRG expression of GlyT1 was not altered and NR1 was unchanged in DRG 12 days after CCI. GlyT1, but not GlyT2, is expressed in the peripheral sensory nervous system. The co-expression of GlyT1 and NMDA receptors in DRG suggests that GlyT1 regulates glycine concentration at the glycine binding site of the NMDA receptor. Differential regulation of GlyT1 expression in the spinal cord or DRG, however, does not seem to be associated with the development of neuropathic pain.
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PMID:Glycine transporter GlyT1, but not GlyT2, is expressed in rat dorsal root ganglion--Possible implications for neuropathic pain. 2610 30