Increase of glutamate in satellite glial cells of the trigeminal ganglion in a rat model of craniofacial neuropathic pain.

Introduction: Satellite glial cells (SGCs) that envelop the cell bodies of neurons in sensory ganglia have been shown to both release glutamate, and be activated by glutamate in the context of nociceptive signaling. However, little is known about the subpopulations of SGCs that are activated following nerve injury and whether glutamate mechanisms in the SGCs are involved in the pathologic pain.

Methods: To address this issue, we used light and electron microscopic immunohistochemistry to examine the change in the glutamate levels in the SGCs and the structural relationship between neighboring neurons in the trigeminal ganglion (TG) in a rat model of craniofacial neuropathic pain, CCI-ION.

Mediation of mPFC-LHb pathway in acupuncture inhibition of cocaine psychomotor activity.

The medial prefrontal cortex (mPFC) and the lateral habenula (LHb) play roles in drug addiction and cognitive functions. Our previous studies have suggested that acupuncture at Shenmen (HT7) points modulates mesolimbic reward system in order to suppress drug-induced addiction behaviours. To explore whether an mPFC-LHb circuit mediates the inhibitory effects of acupuncture on addictive behaviours, we examined the projection from mPFC to LHb, excitation of mPFC neurons during acupuncture stimulation, the effects of optogenetic modulation of mPFC-LHb on HT7 inhibition of cocaine-induced locomotion and the effect of mPFC lesion on HT7 inhibition of nucleus accumbens (NAc) dopamine release.

Peptides derived from high voltage-gated calcium channel β subunit reduce blood pressure in rats.

The β subunits of high voltage-gated calcium channels (HGCCs) are essential for optimal channel functions such as channel gating, activation-inactivation kinetics, and trafficking to the membrane. In this study, we report for the first time the potent blood pressure-reducing effects of peptide fragments derived from the β subunits in anesthetized and non-anesthetized rats. Intravenous administration of 16-mer peptide fragments derived from the interacting regions of the β1 [cacb1(344-359)], β2 [cacb2(392-407)], β3 [cacb3(292-307)], and β4 [cacb4(333-348)] subunits with the main α-subunit of HGCC decreased arterial blood pressure in a dose-dependent manner for 5-8 min in anesthetized rats.

Spinal orexin A attenuates opioid-induced mechanical hypersensitivity in the rat.

Background: Repeated administration of opioid analgesics for pain treatment can produce paradoxical hyperalgesia via peripheral and/or central mechanisms. Thus, this study investigated whether spinally (centrally) administered orexin A attenuates opioid-induced hyperalgesia (OIH).

Methods: [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), a selective μ-opioid receptor agonist, was used to induce mechanical hypersensitivity and was administered intradermally (4 times, 1-hour intervals) on the rat hind paw dorsum.

Voltage-dependent calcium channel β subunit-derived peptides reduce excitatory neurotransmission and arterial blood pressure.

Aims: Voltage-dependent calcium channels (VDCCs) play an important role in various physiological functions in the nervous system and the cardiovascular system. In L-, N-, P/Q-, and R-type VDCCs, β subunit assists the channels for membrane targeting and modulates channel properties. In this study, we investigated whether an inhibition of the β subunit binding to α subunit, the pore-forming main subunit of VDCCs, have any effect on channel activation and physiological functions.

Endogenous TRPC channels mediate Ca signals and trigeminal synaptic plasticity induced by mGluR5.

Aims: Metabotropic glutamate receptor 5 (mGluR5), a member of group I mGluR, exerts its effect via elevation of intracellular Ca level. We here characterized Ca signals in the tsA201 cells transfected with mGluR5 and investigated the role of passages for mGluR5-induced Ca signals in synaptic plasticity.

Main Methods: Using a genetically encoded Ca indicator, GCamp2, Ca signals were reliably induced by bath application of (S)-3,5-dihydroxyphenylglycine, the group I mGluR agonist, in the tsA201 cells transfected with mGluR5.

Trigeminal long-term potentiation as a cellular substrate for migraine.

Most previous studies suggest that the subnucleus caudalis (Vc) of spinal trigeminal nucleus (Vsp) plays a key role in the generation and maintenance of migraine, a type of primary headache, by participating in the trigeminovascular system. Furthermore, the excitability of the Vc with the stimulation of the peripheral nociceptive fibers innervating the intracranial vessels or dura matter is regarded as a main cellular substrate for migraine. Here, a revised hypothesis is introduced, reinforcing the previous hypothesis and complementing it.

Postsynaptic N-type or P/Q-type calcium channels mediate long-term potentiation by group I metabotropic glutamate receptors in the trigeminal oralis.

Aims: Both N-type and P/Q-type voltage-gated Ca channels (VGCCs) are involved in the induction of long-term potentiation (LTP), the long-lasting increase of synaptic strength, in the central nervous system. To provide further information on the roles of N-type and P/Q-type VGCCs in the induction of LTP at excitatory synapses of trigeminal primary afferents in the spinal trigeminal subnucleus oralis (Vo), we investigated whether they contribute to the induction of LTP by activation of group I metabotropic glutamate receptors (mGluRs).

Main Methods: (S)-3,5-Dihydroxyphenylglycine (DHPG; 10μM for 5min), the group I mGluR agonist, was used to induce LTP of excitatory postsynaptic currents that were evoked in the Vo neurons by stimulating the trigeminal track.

Proteomic analysis of the dorsal spinal cord in the mouse model of spared nerve injury-induced neuropathic pain.

Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to simultaneously analyze hundreds or thousands of proteins differentially expressed in the dorsal horn of the spinal cord in rats or dorsal root ganglion of rats with certain type of peripheral nerve injury. However, a proteomic study using a mouse model of neuropathic pain could be attempted because of abundant protein database and the availability of transgenic mice.

Electromagnetized gold nanoparticles mediate direct lineage reprogramming into induced dopamine neurons in vivo for Parkinson's disease therapy.

Electromagnetic fields (EMF) are physical energy fields generated by electrically charged objects, and specific ranges of EMF can influence numerous biological processes, which include the control of cell fate and plasticity. In this study, we show that electromagnetized gold nanoparticles (AuNPs) in the presence of specific EMF conditions facilitate an efficient direct lineage reprogramming to induced dopamine neurons in vitro and in vivo. Remarkably, electromagnetic stimulation leads to a specific activation of the histone acetyltransferase Brd2, which results in histone H3K27 acetylation and a robust activation of neuron-specific genes.

Activated leukocyte cell adhesion molecule is involved in excitatory synaptic transmission and plasticity in the rat spinal dorsal horn.

Activated leukocyte cell adhesion molecule (ALCAM), a member of type I transmembrane immunoglobulin superfamily of cell adhesion molecule, is expressed in the surface membrane of various cell types including neurons. In the spinal cord dorsal horn (DH), the first gate for the sensory and pain transmission to the brain, the expression and function of ALCAM have not been known yet. Therefore, we here investigate the synaptic function of ALCAM in the substantia gelatinosa (lamina II) of the spinal DH, as well as its expression in the DH.

Essential roles of mGluR1 and inhibitory synaptic transmission in NMDA-independent long-term potentiation in the spinal trigeminal interpolaris.

Aims: Patterns of synaptic activity determine synaptic strengthening or weakening that is typically represented as long-term potentiation (LTP) and long-term depression (LTD), respectively. In the present study, we aim to test whether a conditioning stimulation of the spinal trigeminal subnucleus caudalis (Vc) induces LTP at excitatory synapses in the subnucleus interpolaris (Vi) and to characterize the LTP.

Main Methods: Generally, a presynaptic high-frequency stimulation (HFS) protocol can induce LTP at excitatory synapses in the brain, including the spinal cord.

Spinal Gap Junction Channels in Neuropathic Pain.

Damage to peripheral nerves or the spinal cord is often accompanied by neuropathic pain, which is a complex, chronic pain state. Increasing evidence indicates that alterations in the expression and activity of gap junction channels in the spinal cord are involved in the development of neuropathic pain. Thus, this review briefly summarizes evidence that regulation of the expression, coupling, and activity of spinal gap junction channels modulates pain signals in neuropathic pain states induced by peripheral nerve or spinal cord injury.

Orexin-A modulates excitatory synaptic transmission and neuronal excitability in the spinal cord substantia gelatinosa.

Although intrathecal orexin-A has been known to be antinociceptive in various pain models, the role of orexin-A in antinociception is not well characterized. In the present study, we examined whether orexin-A modulates primary afferent fiber-mediated or spontaneous excitatory synaptic transmission using transverse spinal cord slices with attached dorsal root. Bath-application of orexin-A (100nM) reduced the amplitude of excitatory postsynaptic currents (EPSCs) evoked by electrical stimulation of Aδ- or C-primary afferent fibers.

The relaxing effect of Poncirus fructus and its flavonoid content on porcine coronary artery.

Coronary artery disease is a common occurrence in human, and causes enormous social cost. Poncirus fructus (PF), the dried immature fruits of Poncirus trifoliata Rafinesquem, is used in the treatment of womb contraction and dyspepsia, as a prokinetic, and in improving blood circulation. This study was performed to investigate the effects of PF and some of its flavonoids components on the coronary from the pig.

Differential roles of signal transduction mechanisms in long-term potentiation of excitatory synaptic transmission induced by activation of group I mGluRs in the spinal trigeminal subnucleus oralis.

Group I metabotropic glutamate receptors (mGluR1 and 5) have been implicated in long-term potentiation (LTP), a persistent increase of synaptic efficiency, in the central nervous system including the spinal trigeminal nucleus (Vsp). In the ascending pathway from the caudalis (Vc) to the oralis (Vo) subnuclus in Vsp, it has been shown that the activation of group I mGluRs (mGluR1 and 5) with their agonist (S)-3,5-dihydroxyphenylglycine (DHPG) produces a delayed type of LTP of excitatory synaptic transmission and this LTP was mediated by mGluR1. Further, this study attempts to pharmacologically characterize essential signaling components for the expression of DHPG-induced LTP.

Theta-burst stimulation induces LTP at excitatory and inhibitory synapses in the spinal trigeminal subnucleus interpolaris.

Long-lasting synaptic modifications of excitatory and inhibitory synaptic transmissions induced by theta-burst stimulation (TBS) were examined in the spinal trigeminal subnucleus interpolaris (Vi). We found that conditioning afferents of another subnucleus caudalis (Vc) to the Vi with TBS produced long-term depression (LTD). However, when GABAA and glycine receptors were blocked, the same stimulation paradigm produced long-term potentiation (LTP).

Long-term potentiation by activation of group I metabotropic glutamate receptors at excitatory synapses in the spinal trigeminal subnucleus oralis.

In this study, I examined if activation of group I metabotropic glutamate receptors (mGluRs; mGluR1 and 5) induces long-term potentiation (LTP) at excitatory synapses in the ascending pathway from the spinal trigeminal subnuclei caudalis (Vc) to oralis (Vo), in which group I mGluRs are strongly expressed. As a result, the activation of group I mGluRs produced an initial short-lasting depression and subsequently a delayed type of long-term potentiation (LTP) of excitatory synaptic transmission. Analyses of paired pulse ratio and coefficient of variation indicated that the initial short-lasting depression was induced presynaptically, whereas LTP was expressed postsynaptically.

Ionotropic glutamate receptors and voltage-gated Ca²⁺ channels in long-term potentiation of spinal dorsal horn synapses and pain hypersensitivity.

Over the last twenty years of research on cellular mechanisms of pain hypersensitivity, long-term potentiation (LTP) of synaptic transmission in the spinal cord dorsal horn (DH) has emerged as an important contributor to pain pathology. Mechanisms that underlie LTP of spinal DH neurons include changes in the numbers, activity, and properties of ionotropic glutamate receptors (AMPA and NMDA receptors) and of voltage-gated Ca²⁺ channels. Here, we review the roles and mechanisms of these channels in the induction and expression of spinal DH LTP, and we present this within the framework of the anatomical organization and synaptic circuitry of the spinal DH.

The primo vascular structures alongside nervous system: its discovery and functional limitation.

The primo vascular structures comprising primo nodes and vessels (originally called Bonghan corpuscles and ducts, resp.) have recently been suggested to be the anatomical correlate of acupuncture, a therapeutic technique used in oriental medicine. Although the primo vascular structures have been observed in many parts of animals, including the nervous system, using anatomical methodologies, its physiological functions are still unclear.

Localized calcineurin confers Ca2+-dependent inactivation on neuronal L-type Ca2+ channels.

Excitation-driven entry of Ca(2+) through L-type voltage-gated Ca(2+) channels controls gene expression in neurons and a variety of fundamental activities in other kinds of excitable cells. The probability of opening of Ca(V)1.2 L-type channels is subject to pronounced enhancement by cAMP-dependent protein kinase (PKA), which is scaffolded to Ca(V)1.

NMDA receptor, PKC and ERK prevent fos expression induced by the activation of group I metabotropic glutamate receptors in the spinal trigeminal subnucleus oralis.

Fos, a protein product of immediate early gene c-fos, has been used as a marker for activation of nociceptive neurons in central nervous system including spinal trigeminal nucleus (Vsp). By noxious stimulation applied to orofacial area, the expression of Fos occurred in the Vsp pars oralis (Vo), the subnucleus receiving inputs from trigeminal primary afferents that predominantly innervate intraoral receptive fields. The present study demonstrates that the in vitro activation of group I metabotropic glutamate receptors (mGluRs; mGluR1 and 5) by bath-application of their well-known agonist (S)-3,5-dihydroxyphenylglycine (DHPG) increased the number of Fos-expressing neurons in the Vo area.

Preventing Extracellular Diffusion of Trigeminal Nitric Oxide Enhances Formalin-induced Orofacial Pain.

Nitric oxide (NO), a diffusible gas, is produced in the central nervous system, including the spinal cord dorsal horn and the trigeminal nucleus, the first central areas processing nociceptive information from periphery. In the spinal cord, it has been demonstrated that NO acts as pronociceptive or antinociceptive mediators, apparently in a concentration-dependent manner. However, the central role of NO in the trigeminal nucleus remains uncertain in support of processing the orofacial nociception.

Signal transduction mechanisms underlying group I mGluR-mediated increase in frequency and amplitude of spontaneous EPSCs in the spinal trigeminal subnucleus oralis of the rat.

Group I mGluRs (mGluR1 and 5) pre- and/or postsynaptically regulate synaptic transmission at glutamatergic synapses. By recording spontaneous EPSCs (sEPSCs) in the spinal trigeminal subnucleus oralis (Vo), we here investigated the regulation of glutamatergic transmission through the activation of group I mGluRs. Bath-applied DHPG (10 microM/5 min), activating the group I mGluRs, increased sEPSCs both in frequency and amplitude; particularly, the increased amplitude was long-lasting.