Milnacipran inhibits glutamatergic N-Methyl-D-Aspartate receptor activity in Spinal Dorsal Horn NeuronsReport as inadecuate




Milnacipran inhibits glutamatergic N-Methyl-D-Aspartate receptor activity in Spinal Dorsal Horn Neurons - Download this document for free, or read online. Document in PDF available to download.

Molecular Pain

, 8:45

First Online: 19 June 2012Received: 02 February 2012Accepted: 19 June 2012

Abstract

BackgroundAntidepressants, which are widely used for treatment of chronic pain, are thought to have antinociceptive effects by blockade of serotonin and noradrenaline reuptake. However, these drugs also interact with various receptors such as excitatory glutamatergic receptors. Thermal hyperalgesia was induced by intrathecal injection of NMDA in rats. Paw withdrawal latency was measured after intrathecal injection of antidepressants. The effects of antidepressants on the NMDA and AMPA-induced responses were examined in lamina II neurons of rat spinal cord slices using the whole-cell patch-clamp technique. The effects of milnacipran followed by application of NMDA on pERK activation were also investigated in the spinal cord.

ResultsIntrathecal injection of milnacipran 0.1 μmol, but not citalopram 0.1 μmol and desipramine 0.1 μmol, followed by intrathecal injection of NMDA 1 μg suppressed thermal hyperalgesia. Milnacipran 100 μM reduced the amplitude of NMDA 56 ± 3 %, 64 ± 5 % of control-, but not AMPA 98 ± 5 %, 97 ± 5 % of control-mediated currents induced by exogenous application and dorsal root stimulation, respectively. Citalopram 100 μM and desipramine 30 μM had no effect on the amplitude of exogenous NMDA-induced currents. The number of pERK-positive neurons in the group treated with milnacipran 100 μM, but not citalopram 100 μM or desipramine 30 μM, followed by NMDA 100 μM was significantly lower compared with the NMDA-alone group.

ConclusionsThe antinociceptive effect of milnacipran may be dependent on the drug’s direct modulation of NMDA receptors in the superficial dorsal horn. Furthermore, in addition to inhibiting the reuptake of monoamines, glutamate NMDA receptors are also important for analgesia induced by milnacipran.

KeywordsAntidepressants N-methyl-D-aspartate NMDA Receptor Spinal Analgesia Electronic supplementary materialThe online version of this article doi:10.1186-1744-8069-8-45 contains supplementary material, which is available to authorized users.

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Author: Tatsuro Kohno - Masafumi Kimura - Mika Sasaki - Hideaki Obata - Fumimasa Amaya - Shigeru Saito

Source: https://link.springer.com/



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