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Effects of pregabalin on D‐serine content and NMDA receptor‐mediated synaptic transmission in the mouse spinal cord (1129.9)
Author(s) -
Matsuzawa Rie,
Takasusuki Toshifumi,
Maekawa Masao,
Yamaguchi Shigaki,
Hori Yuuichi
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1129.9
Subject(s) - nmda receptor , sciatic nerve , spinal cord , chemistry , lumbar spinal cord , excitatory postsynaptic potential , neuropathic pain , neurotransmission , postsynaptic potential , pregabalin , allodynia , anesthesia , nociception , neuroscience , pharmacology , receptor , hyperalgesia , medicine , biochemistry , biology
The anticonvulsant pregabalin (PGB) is used to relieve neuropathic pain. It has been shown that PGB binds to presynaptic calcium channels and subsequently inhibits transmitter release. Additionally, a preponderance of the evidence raises the possibility of other mechanisms independent of binding to calcium channels. In the present experiments, we have studied the effects of PGB on D‐serine content and NMDA receptor‐mediated synaptic transmission in the spinal cord dorsal horn. Experiments were performed on adult ICR mice. The sciatic nerve was partially ligated under halothane anesthesia. Mechanical allodynia was assessed by von Frey filaments. PGB (30‐50 mg/kg body weight) was intraperitonealy injected daily for 5‐7 days. The lumbar spinal cord was removed, homogenized, and ultrafiltrated. Supernatant samples were treated with Marfey's reagent and analyzed with liquid chromatography‐mass spectrometry for D‐serine concentration. Tight‐seal whole‐cell recordings were made from neurons in the superficial dorsal horn of spinal cord slices. Excitatory postsynaptic currents (EPSCs) were evoked by electrical stimulation. D‐serine content was 9.9±1.0 nM/g of wet tissue in sciatic nerve‐ligated mice (n=6), which was significantly larger than that in sham‐operated mice (7.9±0.8 nM/g, p < 0.05). PGB considerably decreased D‐serine content to 6.0±0.9 nM/g (n=6, p < 0.05, vs. sciatic nerve‐ligated mice). PGB decreased the NMDA/non‐NMDA ratio of the EPSC amplitude, and shortened the decay phase of the NMDA component of the EPSCs. These observations suggest that PGB decreases D‐serine concentration and thereby affects synaptic plasticity. Grant Funding Source : Supported by a grant from the Japan Society for the Promotion of Science (23500468 to Y.H.).