scholarly journals Intravenous administration of lidocaine directly acts on spinal dorsal horn and produces analgesic effect: An in vivo patch-clamp analysis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Miyuki Kurabe ◽  
Hidemasa Furue ◽  
Tatsuro Kohno

Abstract Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, although the underlying mechanisms remains unclear. Here, we hypothesized that intravenous lidocaine acts on spinal cord neurons and induces analgesia in acute pain. We therefore examined the action of intravenous lidocaine in the spinal cord using the in vivo patch-clamp technique. We first investigated the effects of intravenous lidocaine using behavioural measures in rats. We then performed in vivo patch-clamp recording from spinal substantia gelatinosa (SG) neurons. Intravenous lidocaine had a dose-dependent analgesic effect on the withdrawal response to noxious mechanical stimuli. In the electrophysiological experiments, intravenous lidocaine inhibited the excitatory postsynaptic currents (EPSCs) evoked by noxious pinch stimuli. Intravenous lidocaine also decreased the frequency, but did not change the amplitude, of both spontaneous and miniature EPSCs. However, it did not affect inhibitory postsynaptic currents. Furthermore, intravenous lidocaine induced outward currents in SG neurons. Intravenous lidocaine inhibits glutamate release from presynaptic terminals in spinal SG neurons. Concomitantly, it hyperpolarizes postsynaptic neurons by shifting the membrane potential. This decrease in the excitability of spinal dorsal horn neurons may be a possible mechanism for the analgesic action of intravenous lidocaine in acute pain.

2000 ◽  
Vol 84 (4) ◽  
pp. 2171-2174 ◽  
Author(s):  
Keita Narikawa ◽  
Hidemasa Furue ◽  
Eiichi Kumamoto ◽  
Megumu Yoshimura

To know a functional role of inhibitory synaptic responses in transmitting noxious and innoxious information from the periphery to the rat spinal dorsal horn, we examined inhibitory postsynaptic currents (IPSCs) elicited in substantia gelatinosa (SG) neurons by mechanical stimuli applied to the skin using the newly developed in vivo patch-clamp technique. In the majority (80%) of SG neurons examined, a brush stimulus applied to the ipsilateral hind limb produced a barrage of IPSCs that persisted during the stimulus, while a pinch stimulus evoked IPSCs only at its beginning and end. The pinch-evoked IPSCs may have been caused by a touch that occurs at the on/off time of the pinch. The evoked IPSCs were blocked by either a glycine-receptor antagonist, strychnine (4 μM), or a GABAA-receptor antagonist, bicuculline (20 μM). All SG neurons examined received inhibitory inputs from a wide area throughout the thigh and lower leg. When IPSCs were examined together with excitatory postsynaptic currents (EPSCs) in the same neurons, a brush evoked a persistent activity of both IPSCs and EPSCs during the stimulus while a pinch evoked such an activity of EPSCs but not IPSCs. It is suggested that innoxious mechanical stimuli activate a GABAergic or glycinergic circuitry in the spinal dorsal horn. This inhibitory transmission may play an important role in the modulation of noxious information in the SG.


2019 ◽  
Vol Volume 12 ◽  
pp. 1269-1278 ◽  
Author(s):  
Motoki Sonohata ◽  
Atsushi Doi ◽  
Toshiharu Yasaka ◽  
Daisuke Uta ◽  
Masaaki Mawatari ◽  
...  

2004 ◽  
Vol 1269 ◽  
pp. 69-72 ◽  
Author(s):  
Hidemasa Furue ◽  
Go Kato ◽  
Ji Hoon Kim ◽  
Byung-Il Min ◽  
Toshihiko Katafuchi ◽  
...  

2009 ◽  
Vol 13 (S1) ◽  
Author(s):  
M. Gassner ◽  
M. Wagner ◽  
H. Fischer ◽  
R. Drdla ◽  
T. Jäger ◽  
...  

2015 ◽  
Vol 56 (5) ◽  
pp. 1307 ◽  
Author(s):  
Hee Youn Hwang ◽  
Enji Zhang ◽  
Sangil Park ◽  
Woosuk Chung ◽  
Sunyeul Lee ◽  
...  

1999 ◽  
Vol 4 (2) ◽  
pp. 192-200 ◽  
Author(s):  
Henrik Gustafsson ◽  
Guilherme de Araujo Lucas ◽  
Eva Schött ◽  
Carl-Olav Stiller ◽  
Pawel Alster ◽  
...  

Glia ◽  
2018 ◽  
Vol 67 (3) ◽  
pp. 482-497 ◽  
Author(s):  
Xisheng Yan ◽  
Fen Li ◽  
Dylan W. Maixner ◽  
Ruchi Yadav ◽  
Mei Gao ◽  
...  

2011 ◽  
Vol 105 (6) ◽  
pp. 3010-3021 ◽  
Author(s):  
Hui-Juan Hu ◽  
Robert W. Gereau

Metabotropic glutamate (mGlu) receptors play important roles in the modulation of nociception. Previous studies demonstrated that mGlu5 modulates nociceptive plasticity via activation of ERK signaling. We have reported recently that the Kv4.2 K+ channel subunit underlies A-type currents in spinal cord dorsal horn neurons and that this channel is modulated by mGlu5-ERK signaling. In the present study, we tested the hypothesis that modulation of Kv4.2 by mGlu5 occurs in excitatory spinal dorsal horn neurons. With the use of a transgenic mouse strain expressing enhanced green fluorescent protein (GFP) under control of the promoter for the γ-amino butyric acid (GABA)-synthesizing enzyme, glutamic acid decarboxylase 67 (GAD67), we found that these GABAergic neurons express less Kv4.2-mediated A-type current than non-GAD67-GFP neurons. Furthermore, the mGlu1/5 agonist, (R,S)-3,5-dihydroxyphenylglycine, had no modulatory effects on A-type currents or neuronal excitability in this subgroup of GABAergic neurons but robustly modulated A-type currents and neuronal excitability in non-GFP-expressing neurons. Immunofluorescence studies revealed that Kv4.2 was highly colocalized with markers of excitatory neurons, such as vesicular glutamate transporter 1/2, PKCγ, and neurokinin 1, in cultured dorsal horn neurons. These results indicate that mGlu5-Kv4.2 signaling is associated with excitatory dorsal horn neurons and suggest that the pronociceptive effects of mGlu5 activation in the spinal cord likely involve enhanced excitability of excitatory neurons.


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