Baclofen inhibition of dorsal root-evoked inhibitory postsynaptic currents in substantia gelatinosa neurons of rat spinal cord slice

2001 ◽  
Vol 900 (2) ◽  
pp. 320-323 ◽  
Author(s):  
Kun Yang ◽  
Yu-Peng Feng ◽  
Yun-Qing Li
2000 ◽  
Vol 92 (2) ◽  
pp. 507-507 ◽  
Author(s):  
Tatsuro Kohno ◽  
Eiichi Kumamoto ◽  
Hiroshi Baba ◽  
Toyofumi Ataka ◽  
Manabu Okamoto ◽  
...  

Background Although intrathecal administration of midazolam has been found to produce analgesia, how midazolam exerts this effect is not understood fully at the neuronal level in the spinal cord. Methods The effects of midazolam on either electrically evoked or spontaneous inhibitory transmission and on a response to exogenous gamma-aminobutyric acid (GABA), a GABA(A)-receptor agonist, muscimol, or glycine were evaluated in substantia gelatinosa neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique. Results Bath-applied midazolam (1 microM) prolonged the decay phase of evoked and miniature inhibitory postsynaptic currents (IPSCs), mediated by GABA(A) receptors, without a change in amplitudes, while not affecting glycine receptor-mediated miniature inhibitory postsynaptic currents in both the decay phase and the amplitude. Either GABA- or muscimol-induced currents were enhanced in amplitude by midazolam (0.1 microM) in a manner sensitive to a benzodiazepine receptor antagonist, flumazenil (1 microM); glycine currents were, however, unaltered by midazolam. Conclusions Midazolam augmented both the duration of GABA-mediated synaptic current and the amplitude of GABA-induced current by acting on the GABA(A)-benzodiazepine receptor in substantia gelatinosa neurons; this would increase the inhibitory GABAergic transmission. This may be a possible mechanism for antinociception by midazolam.


1991 ◽  
Vol 66 (6) ◽  
pp. 1941-1950 ◽  
Author(s):  
D. S. Magnuson ◽  
A. H. Dickenson

1. Extracellular recordings were made from 95 dorsal horn neurons in a sagittal slice preparation of rat spinal cord. Neurons were synaptically activated by electrical stimulation of the dorsal root entry zone (n = 72) or driven by pressure ejection of L-glutamate into the substantia gelatinosa (SG; n = 23). For the majority of neurons low-intensity electrical stimuli evoked a burst of spikes with short latency (early firing). An increase in the stimulus intensity evoked the early firing followed by a characteristic prolonged period of activity (late firing). 2. The patterns of synaptically induced activity observed from neurons located in the SG (n = 45) and in deeper laminae (n = 27) were similar. Early and late firing of both SG and deep neurons was reduced by the nonspecific excitatory amino acid antagonist kynurenate. Raising [Mg2+] in the superfusate to 5 from 2.0 mM selectively reduced the late firing of both SG and deep neurons. These findings suggest that fibers present in the dorsal root zone make excitatory amino acid-mediated synapses with dorsal horn neurons. 3. The majority of deep neurons showed reduced responses to electrical stimuli in the presence of morphine, mimicking the findings reported in vivo. Naloxone reversed morphine inhibitions or, when applied to morphine-naive slices, caused modest increases in the responses of some deep neurons. 4. Most neurons located in the SG had their responses enhanced by morphine (late firing: 86.5 +/- 19.6%, mean +/- SE) and were inhibited by naloxone (-78.3 +/- 22.7%). Morphine-induced enhancements often persisted long after the morphine had washed out of the bath. Inhibitions by naloxone, whether pre- or postmorphine, were short lived; and responses generally returned to either control or morphine-enhanced levels on washout of the naloxone. 5. The gamma-aminobutyric acid (GABA) antagonist bicuculline, applied to GABA-naive slices, caused an increase in response of SG neurons while slightly depressing activity of deep neurons. A tonic release or presence of endogenous GABA, affecting neurons that are inhibited by exogenously applied GABA, may be responsible for the observed action of bicuculline. 6. Intracellular recordings were made from a further 32 dorsal horn neurons located in the translucent band of the spinal cord slices. Of 11 neurons examined, 5 showed increased input resistance (Rin) and were depolarized in response to morphine applied in the superfusate. One neuron showed no change in Rin or potential with morphine, whereas 5 of the 11 were hyperpolarized with decreased Rin.(ABSTRACT TRUNCATED AT 400 WORDS)


2000 ◽  
Vol 92 (2) ◽  
pp. 485-485 ◽  
Author(s):  
Hiroshi Baba ◽  
Peter A. Goldstein ◽  
Manabu Okamoto ◽  
Tatsuro Kohno ◽  
Toyofumi Ataka ◽  
...  

Background It has been reported previously that norepinephrine, when applied to the spinal cord dorsal horn, excites a subpopulation of dorsal horn neurons, presumably inhibitory interneurons. In the current study, the authors tested whether norepinephrine could activate inhibitory interneurons, specifically those that are "GABAergic." Methods A transverse slice was obtained from a segment of the lumbar spinal cord isolated from adult male Sprague-Dawley rats. Whole-cell patch-clamp recordings were made from substantia gelatinosa neurons using the blind patch-clamp technique. The effects of norepinephrine on spontaneous GABAergic inhibitory postsynaptic currents were studied. Results In the majority of substantia gelatinosa neurons tested, norepinephrine (10-60 microM) significantly increased both the frequency and the amplitude of GABAergic inhibitory postsynaptic currents. These increases were blocked by tetrodotoxin (1 microM). The effects of norepinephrine were mimicked by the alpha1-receptor agonist phenylephrine (10-80 microM) and inhibited by the alpha1-receptor-antagonist WB-4101 (0.5 microM). Primary-afferent-evoked polysynaptic excitatory postsynaptic potentials or excitatory postsynaptic currents in wide-dynamic-range neurons of the deep dorsal horn were also attenuated by phenylephrine (40 microM). Conclusion The observations suggest that GABAergic interneurons possess somatodendritic alpha1 receptors, and activation of these receptors excites inhibitory interneurons. The alpha1 actions reported herein may contribute to the analgesic action of intrathecally administered phenylephrine.


1999 ◽  
Vol 830 (2) ◽  
pp. 268-273 ◽  
Author(s):  
Kun Yang ◽  
Eiichi Kumamoto ◽  
Hidemasa Furue ◽  
Yun-Qing Li ◽  
Megumu Yoshimura

2000 ◽  
Vol 92 (2) ◽  
pp. 473-473 ◽  
Author(s):  
Hiroshi Baba ◽  
Koki Shimoji ◽  
Megumu Yoshimura

Background The activation of descending norepinephrine-containing fibers from the brain stem inhibits nociceptive transmission at the spinal level. How these descending noradrenergic pathways exert the analgesic effect is not understood fully. Membrane hyperpolarization of substantia gelatinosa (Rexed lamina II) neurons by the activation of alpha2 receptors may account for depression of pain transmission. In addition, it is possible that norepinephrine affects transmitter release in the substantia gelatinosa. Methods Adult male Sprague-Dawley rats (9-10 weeks of age, 250-300 g) were used in this study. Transverse spinal cord slices were cut from the isolated lumbar cord. The blind whole-cell patch-clamp technique was used to record from neurons. The effects of norepinephrine on the frequency and amplitude of miniature excitatory and inhibitory postsynaptic currents were evaluated. Results In the majority of substantia gelatinosa neurons tested, norepinephrine (10-100 microM) dose-dependently increased the frequency of gamma-aminobutyric acid (GABA)ergic and glycinergic miniature inhibitory postsynaptic currents; miniature excitatory postsynaptic currents were unaffected. This augmentation was mimicked by an alpha1-receptor agonist, phenylephrine (10-60 microM), and inhibited by alpha1-receptor antagonists prazosin (0.5 microM) and 2-(2,6-dimethoxyphenoxyethyl) amino-methyl-1,4-benzodioxane (0.5 microM). Neither postsynaptic responsiveness to exogenously applied GABA and glycine nor the kinetics of GABAergic and glycinergic inhibitory postsynaptic currents were affected by norepinephrine. Conclusion These results suggest that norepinephrine enhances inhibitory synaptic transmission in the substantia gelatinosa through activation of presynaptic alpha1 receptors, thus providing a mechanism underlying the clinical use of alpha1 agonists with local anesthetics in spinal anesthesia.


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