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Effects of baclofen on mechanical noxious and innocuous transmission in the spinal dorsal horn of the adult rat: in vivo patch‐clamp analysis
Author(s) -
Fukuhara Kaori,
Katafuchi Toshihiko,
Yoshimura Megumu
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12345
Subject(s) - baclofen , excitatory postsynaptic potential , neurotransmission , chemistry , postsynaptic potential , neuroscience , postsynaptic current , agonist , patch clamp , biophysics , electrophysiology , inhibitory postsynaptic potential , receptor , biology , biochemistry
The effects of a GABA B agonist, baclofen, on mechanical noxious and innocuous synaptic transmission in the substantia gelatinosa (SG) were investigated in adult rats with the in vivo patch‐clamp technique. Under current‐clamp conditions, perfusion with baclofen (10 μ m ) on the surface of the spinal cord caused hyperpolarisation of SG neurons and a decrease in the number of action potentials elicited by pinch and touch stimuli applied to the receptive field of the ipsilateral hindlimb. The suppression of action potentials was preserved under blockade of postsynaptic G‐proteins, although baclofen‐induced hyperpolarisation was completely blocked. These findings suggest presynaptic effects of baclofen on the induced action potentials. Under voltage‐clamp conditions, application of baclofen reduced the frequency, but not the amplitude, of miniature excitatory postsynaptic currents ( mEPSC s), whereas the GABA B receptor antagonist CGP55845 increased the frequency of mEPSC s without affecting the amplitude. Furthermore, application of a GABA uptake inhibitor, nipecotic acid, decreased the frequency of mEPSC s; this effect was blocked by CGP55845, but not by the GABA A antagonist bicuculline. Both the frequency and the amplitude of the pinch‐evoked barrage of excitatory postsynaptic currents (EPSCs) were suppressed by baclofen in a dose‐dependent manner. The frequency and amplitude of touch‐evoked EPSCs was also suppressed by baclofen, but the suppression was significantly smaller than that of pinch‐evoked EPSCs. We conclude that mechanical noxious transmission is presynaptically blocked through GABA B receptors in the SG, and is more effectively suppressed than innocuous transmission, which may account for a part of the mechanism of the efficient analgesic effects of baclofen.