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Yue HY, Fujita T, Kumamoto E. Biphasic modulation by galanin of excitatory synaptic transmission in substantia gelatinosa neurons of adult rat spinal cord slices. J Neurophysiol 105: 2337-2349, 2011. First published March 16, 2011 doi:10.1152/jn.00991.2010.-Although intrathecally administrated galanin modulates nociceptive transmission in a biphasic manner, this has not been fully examined previously. In the present study, the action of galanin on synaptic transmission in the substantia gelatinosa (SG) neurons of adult rat spinal cord slices was examined, using the whole cell patch-clamp technique. Galanin concentration-dependently increased the frequency of spontaneous excitatory postsynaptic current (EPSC; EC 50 ϭ 2.0 nM) without changing the amplitude, indicating a presynaptic effect. This effect was reduced in a Ca 2ϩ -free, or voltage-gated Ca 2ϩ channel blocker La 3ϩ -containing Krebs solution and was produced by a galanin type-2/3 receptor (GalR2/R3) agonist, galanin 2-11, but not by a galanin type-1 receptor (GalR1) agonist, M617. Galanin also concentration-dependently produced an outward current at Ϫ70 mV (EC 50 ϭ 44 nM), although this appeared to be contaminated by a small inward current. This outward current was mimicked by M617, but not by galanin 2-11. Moreover, galanin reduced monosynaptic A␦-fiber-and C-fiber-evoked EPSC amplitude; the former reduction was larger than the latter. A similar action was produced by galanin 2-11, but not by M617. Spontaneous and focally evoked inhibitory (GABAergic and glycinergic) transmission was unaffected by galanin. These findings indicate that galanin at lower concentrations enhances the spontaneous release of L-glutamate from nerve terminals by Ca 2ϩ entry from the external solution following GalR2/R3 activation, whereas galanin at higher concentrations also produces a membrane hyperpolarization by activating GalR1. Moreover, galanin reduces L-glutamate release onto SG neurons from primary afferent fibers by activating GalR2/R3. These effects could partially contribute to the behavioral effect of galanin. pain; patch clamp; spinal dorsal horn GALANIN, a 29/30-amino acid peptide, was first extracted from porcine upper intestines in 1983 (Tatemoto et al. 1983). Subsequently, this peptide was reported to extensively exist in the peripheral and central nervous systems (CNS) (Lang et al. 2007). Recently, it was established that galanin serves as a neurotransmitter or neuromodulator in various physiological functions, including feeding and pain (Hökfelt 2005;Lang et al. 2007;Liu and Hökfelt 2002). There are three types of G protein-coupled metabotropic receptors (GalR1, GalR2, GalR3) for galanin (Lang et al. 2007).There is much evidence demonstrating that galanin plays a role in regulating nociceptive transmission to the spinal dorsal horn from the periphery. First, galanin-immunoreactivity, GalR1, GalR2, and GalR3 mRNAs and proteins exist in the rat The substantia gelatinosa (SG; lamina II of Rexed) of the spinal dorsal horn is thought to play an important role in ...

Transient receptor potential (TRP) channels are thought to play a role in regulating nociceptive transmission to spinal substantia gelatinosa (SG) neurons. It remains to be unveiled whether the TRP channels in the central nervous system are different in property from those involved in receiving nociceptive stimuli in the peripheral nervous system. We examined the effect of the vanilloid compound zingerone, which activates TRPV1 channels in the cell body of a primary afferent neuron, on glutamatergic excitatory transmission in the SG neurons of adult rat spinal cord slices by using the whole cell patch-clamp technique. Bath-applied zingerone reversibly and concentration-dependently increased spontaneous excitatory postsynaptic current (EPSC) frequency. This effect was accompanied by an inward current at -70 mV that was resistant to glutamate receptor antagonists. These zingerone effects were repeated and persisted in Na(+)-channel blocker tetrodotoxin-, La(3+)-, or IP3-induced Ca(2+)-release inhibitor 2-aminoethoxydiphenyl borate-containing or Ca(2+)-free Krebs solution. Zingerone activity was resistant to the selective TRPV1 antagonist capsazepine but sensitive to the nonselective TRP antagonist ruthenium red, the TRPA1 antagonist HC-030031, and the Ca(2+)-induced Ca(2+)-release inhibitor dantrolene. TRPA1 agonist allyl isothiocyanate but not capsaicin inhibited the facilitatory effect of zingerone. On the other hand, zingerone reduced monosynaptically evoked EPSC amplitudes, as did TRPA1 agonists. Like allyl isothiocyanate, zingerone enhanced GABAergic spontaneous inhibitory transmission in a manner sensitive to tetrodotoxin. We conclude that zingerone presynaptically facilitates spontaneous excitatory transmission, probably through Ca(2+)-induced Ca(2+)-release mechanisms, and produces a membrane depolarization in SG neurons by activating TRPA1 but not TRPV1 channels.

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