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Nitric Oxide Derived from Neuronal NOS Inhibits Spinal Synaptic Transmission and Neuropathic Pain
Author(s) -
Chen ShaoRui,
Jin XiaoGao,
Chen Hong,
Pan HuiLin
Publication year - 2015
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.29.1_supplement.770.2
Subject(s) - inhibitory postsynaptic potential , neurotransmission , neuroscience , excitatory postsynaptic potential , glutamatergic , neuropathic pain , nmda receptor , soluble guanylyl cyclase , chemistry , postsynaptic potential , nociception , nerve injury , glutamate receptor , allodynia , nitric oxide , hyperalgesia , biology , receptor , biochemistry , organic chemistry , guanylate cyclase
The role of nitric oxide (NO) in nociceptive transduction and transmission remains controversial. In this study, we determined how NO affects synaptic transmission at the spinal level in a rat model of neuropathic pain. Bath application of the NO precursor L‐arginine or the NO donor SNAP significantly increased the frequency of spontaneous glycinergic inhibitory postsynaptic currents (IPSCs) of spinal lamina II neurons without affecting GABAergic IPSCs in both control and nerve‐injured rats. Inhibition of the soluble guanylyl cyclase blocked the potentiating effect of NO on glycinergic IPSCs. L‐arginine or SNAP significantly inhibited glutamatergic excitatory postsynaptic currents (EPSCs) monosynaptically evoked from the dorsal root. Also, L‐arginine or SNAP significantly attenuated the amplitude of evoked NMDA receptor currents and puff NMDA‐elicited currents in spinal lamina II neurons in both control and nerve‐injured rats. Inhibition of neuronal NOS or knockdown of neuronal NOS with siRNA blocked the inhibitory effect of L‐arginine, but not SNAP, on evoked EPSCs and NMDA receptor currents. Furthermore, blocking the S‐nitrosylation reaction with N‐ethylmaleimide abolished the inhibitory effects of NO on evoked EPSCs and NMDA receptor currents recorded from lamina II neurons and voltage‐activated calcium channel currents of dorsal root ganglia in control and nerve‐injured rats. Additionally, intrathecal injection of L‐arginine or SNAP significantly attenuated tactile allodynia and mechanical hyperalgesia induced by nerve injury. These findings suggest that NO derived from neuronal NOS inhibits glutamatergic synaptic transmission at the spinal level and neuropathic pain through S‐nitrosylation of voltage‐activated calcium channels and NMDA receptors.