Presynaptic inhibition by baclofen of miniature EPSCs and IPSCs in substantia gelatinosa neurons of the adult rat spinal dorsal horn.
Intrathecal administration of baclofen, a GABA(B)-receptor agonist, affects pain behavior induced by formalin in a biphasic manner; baclofen at low doses enhances pain while producing antinociception at high doses. This may be due to the fact that baclofen modulates each of excitatory and inhibitory transmission in the dorsal horn of the spinal cord with a distinct sensitivity, resulting in a biphasic action on pain transmission. To address this issue, we examined the actions of baclofen on miniature excitatory (glutamatergic) and inhibitory (GABAergic) postsynaptic currents (mEPSCs and mIPSCs, respectively) in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by using the whole-cell voltage-clamp technique. Baclofen reduced the frequency of both mEPSC and mIPSC without a change in their amplitudes. These actions were dose-dependent in a concentration range of 0.1-100 microM; the effective concentrations for the half-inhibition of mEPSC and mIPSC frequency were 4.44+/-0. 60 microM (n=7) and 4.31+/-0.77 microM (n=6), respectively. These results indicate that each of glutamatergic and GABAergic nerve terminals in the SG is endowed with the GABA(B) receptor, the activation of which depresses the release of neurotransmitter from the terminal; this provides a cellular basis for the modulation of pain by baclofen. It is suggested from a similar affinity for baclofen of the GABA(B) receptors on both terminals that the baclofen-induced biphasic action on pain behaviors cannot be accounted for by only its presynaptic actions in the SG and that other actions such as an inhibitory action of baclofen on postsynaptic neurons also have to be taken into consideration.
Iyadomi
Minako
M
Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan Department of Community Health Science, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan Department of Anesthesiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Iyadomi
Ikuo
I
Kumamoto
Eiichi
E
Tomokuni
Katsumaro
K
Yoshimura
Megumu
M
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D018755:GABA Agonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects; D018080:Receptors, GABA-B / Q000187:drug effects; D017661:Receptors, Presynaptic / Q000187:drug effects*; D013376:Substantia Gelatinosa / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
D018755:GABA Agonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D017661:Receptors, Presynaptic; D001418:Baclofen