Skin health survey on atopic dermatitis among Japanese children: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

Background: Precise skin phenotypic data are indispensable in accurately diagnosing atopic dermatitis (AD). Therefore, this study examined the interobserver concordance for AD and non-AD diagnoses between two dermatologists. AD prevalence determined by the self-reported physician diagnoses and the diagnoses determined from the United Kingdom (UK) diagnostic criteria were compared with the diagnoses made by the two dermatologists, using data from a skin health survey.

Gabapentin and pregabalin ameliorate mechanical hypersensitivity after spinal cord injury in mice.

The antiepileptic drugs gabapentin and pregabalin exhibit well-established analgesic effects in patients with several neuropathic conditions. In the present study, we examined their effects on mechanical hypersensitivity in mice subjected to weight-drop spinal cord injury. Hindlimb motor function and mechanical hypersensitivity were evaluated using the Basso-Beattie-Bresnahan (BBB) locomotor rating scale and the von Frey test, respectively, for 4 weeks after spinal cord injury.

Glycine transporter blockade ameliorates motor ataxia in a mouse model of spinocerebellar atrophy.

Ataxic movement, the common major symptom of spinocerebellar atrophy, has been considered to involve impaired glutamatergic excitatory neurotransmission in the cerebellum. Considering the therapeutic importance of ataxia control, we assessed the effectiveness of increasing the extracellular concentration of glycine by administering it exogenously or via blockade of glycine transporter 1, using its selective inhibitors sarcosine and N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine (NFPS), for amelioration of motor ataxia in a mouse model of spinocerebellar atrophy developing after neonatal treatment with cytosine beta-D-arabinofuranoside. Intracerebroventricular (i.

Neurochemical evidence that supraspinally administered gabapentin activates the descending noradrenergic system after peripheral nerve injury.

We have previously demonstrated that gabapentin supraspinally activates the descending noradrenergic system to produce analgesic effects after peripheral nerve injury. To further establish the neurochemical basis for its supraspinally mediated analgesic action, concentrations of spinal noradrenaline, 4-hydroxy-3-methoxyphenylglycol (MHPG), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and dopamine were measured using high-performance liquid chromatography in a murine neuropathic pain model that was prepared by partial ligation of the sciatic nerve (the Seltzer model). Intracerebroventricularly (i.

Phenytoin and carbamazepine delay the initial depression of the population spike upon exposure to in vitro ischemia and promote its post-ischemic functional recovery in rat hippocampal slices.

Antiepileptic drugs have been shown to reduce the severity of neurodegeneration resulting from stroke or brain injury. In the present study, we evaluated the effects of the antiepileptic drugs phenytoin and carbamazepine on the time course of changes in the population spike (PS) during brief oxygen/glucose deprivation (OGD) in the CA1 pyramidal region of rat hippocampal slices in vitro. After introducing simulated ischemia by OGD, the PS was initially inhibited, followed by transient recovery and subsequent reinhibition again concomitantly with disappearance of the presynaptic volley (PV).

Gabapentin depresses C-fiber-evoked field potentials in rat spinal dorsal horn only after induction of long-term potentiation.

C-fiber-evoked field potentials in response to electrical stimulation of the sciatic nerve were recorded in the dorsal horn of the rat lumbar spinal cord, and their long-term potentiation (LTP) was induced by high-frequency stimulation applied on the sciatic nerve as a synaptic model of hypersensitivity underlying an increased efficacy of nociceptive transmission. We evaluated the effect of gabapentin on the basal C-fiber-evoked field potentials and their established LTP. Intravenously administered gabapentin (10 and 30 mg/kg, i.

Fluvoxamine, a selective serotonin reuptake inhibitor, exerts its antiallodynic effects on neuropathic pain in mice via 5-HT2A/2C receptors.

There is an association between depression and chronic pain, and some antidepressants exert antinociceptive effects in humans and laboratory animals. We examined the effects of fluvoxamine, a selective serotonin reuptake inhibitor, on mechanical allodynia and its mechanism of action in the mouse chronic pain model, which was prepared by partially ligating the sciatic nerve. The antiallodynic effect was measured using the von Frey test.

Spinal cord injury-specific depression of monosynaptic spinal reflex transmission by l-5-hydroxytryptophan results from loss of the 5-HT uptake system and not 5-HT receptor supersensitivity.

We studied changes in the spinal segmental reflex and serotonergic (5-HT) responses in rats after spinal cord injury (SCI) produced by the weight-dropping method at the T8 level. The spinal monosynaptic reflex amplitude (MSR) was recorded from the L5 ventral root following stimulation of the ipsilateral L5 dorsal root. The 5-HT precursor l-5-hydroxytryptophan (L-5-HTP) depressed MSR in the spinal cord injured rats but not in normal rats.

Spinal alpha(2)-adrenergic and muscarinic receptors and the NO release cascade mediate supraspinally produced effectiveness of gabapentin at decreasing mechanical hypersensitivity in mice after partial nerve injury.

After partial nerve injury, the central analgesic effect of systemically administered gabapentin is mediated by both supraspinal and spinal actions. We further evaluate the mechanisms related to the supraspinally mediated analgesic actions of gabapentin involving the descending noradrenergic system. Intracerebroventricularly (i.

Spinal ventral root after-discharges as a pain index: involvement of NK-1 and NMDA receptors.

Nociceptive signals are transmitted to the spinal dorsal horn via primary afferent fibers, and the signals induce withdrawal reflexes by activating spinal motoneurons in the ventral horn. Therefore, nociceptive stimuli increase motoneuronal firing and ventral root discharges. This study was aimed to develop a method for the study of pain mechanisms and analgesics by recording ventral root discharges.

Presynaptic I1-imidazoline receptors reduce GABAergic synaptic transmission in striatal medium spiny neurons.

Imidazoline receptors are expressed widely in the CNS. In the present study, whole-cell patch-clamp recordings were made from medium spiny neurons in dorsal striatum slices from the rat brain, and the roles of I1-imidazoline receptors in the modulation of synaptic transmission were studied. Moxonidine, an I1-imidazoline receptor agonist, decreased the GABAA receptor-mediated IPSCs in a concentration-dependent manner.

Taltirelin improves motor ataxia independently of monoamine levels in rolling mouse nagoya, a model of spinocerebellar atrophy.

To examine the relationship between motor ataxia and monoamine levels in the central nervous system, the contents and concentrations of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the cerebellum, brain stem and spinal cord were measured in rolling mouse Nagoya (RMN), a murine model of spinocerebellar atrophy. The tissue weight of the cerebellum and spinal cord, but not that of the brain stem was significantly lower in RMN than in the control group. In RMN, the NA content of the brain stem and spinal cord, but not the cerebellum were decreased relative to the control, and the concentration of NA in the spinal cord was also lower, but not significant.

Centrally mediated antihyperalgesic and antiallodynic effects of zonisamide following partial nerve injury in the mouse.

Some antiepileptic drugs are used clinically to relieve neuropathic pain. We have evaluated the effects and investigated the possible mechanisms of action of zonisamide, an antiepileptic drug, on thermal hyperalgesia and tactile allodynia in a murine chronic pain model that was prepared by partial ligation of the sciatic nerve. Subcutaneously administered zonisamide (10 and 30 mg/kg) produced antihyperalgesic and antiallodynic effects in a dose-dependent manner; these effects were manifested by elevation of the withdrawal threshold in response to a thermal (plantar test) or mechanical (von Frey) stimulus, respectively.

Involvement of supraspinal imidazoline receptors and descending monoaminergic pathways in tizanidine-induced inhibition of rat spinal reflexes.

The neuronal pathways involved in the muscle relaxant effect of tizanidine were examined by measurement of spinal reflexes in rats. Tizanidine (i.v.

Functional alteration of inhibitory influences on spinal motor output in painful diabetic neuropathy in rats.

Diabetes is frequently accompanied by painful polyneuropathies that are mediated by enhanced neuronal excitability in the spinal cord, partly because of decrease in spinal intrinsic inhibitory influences. Changes in spinal excitatory-inhibitory balance may alter spinal segmental motor output. In the study presented here, the mono- and disynaptic (the fastest polysynaptic) reflexes (MSR and DSR, respectively) were recorded from L5 ventral roots in response to stimulation of the ipsilateral L5 dorsal root in spinalized streptozotocin (STZ)-induced diabetic rats with a reduced withdrawal threshold to mechanical stimuli.

Enhanced wind-up of the C-fiber-mediated nociceptive flexor reflex movement following painful diabetic neuropathy in mice.

We examined wind-up of the nociceptive flexor withdrawal responses in diabetic mice that had developed tactile allodynia after treatment with streptozotocin (STZ). In control and STZ-treated mice, simultaneous activation of Adelta- and C-fibers by electrical stimuli at C-fiber intensity delivered to the ventral aspect of the toe elicited a biphasic withdrawal reflex composed of short- and long-latency movements of the ipsilateral hind paw that were respectively mediated by activation of Adelta- and C-fibers. There were no significant differences between control and diabetic mice in the activation threshold of each reflex movement or the amplitude of reflexes elicited by various stimulus intensities.

Role of descending noradrenergic system and spinal alpha2-adrenergic receptors in the effects of gabapentin on thermal and mechanical nociception after partial nerve injury in the mouse.

1. To gain further insight into the mechanisms underlying the antihyperalgesic and antiallodynic actions of gabapentin, a chronic pain model was prepared by partially ligating the sciatic nerve in mice. The mice then received systemic or local injections of gabapentin combined with either central noradrenaline (NA) depletion by 6-hydroxydopamine (6-OHDA) or alpha-adrenergic receptor blockade.

GABAB receptors do not mediate the inhibitory actions of gabapentin on the spinal reflex in rats.

The clinical effectiveness of gabapentin for the treatment of epilepsy, spasticity, and neuropathic pain has been established. The mechanisms responsible for those actions, however, are still not clearly understood. We have recently demonstrated that gabapentin reduces the spinal reflex in rats via mechanisms that do not involve gamma-aminobutyric acid (GABA)A receptors.

Endogenously released 5-hydroxytryptamine depresses the spinal monosynaptic reflex via 5-HT1D receptors.

In the spinal cord, various 5-hydroxytryptamine (5-HT) receptor subtypes are involved in the modulation of motor output. Previously, we have shown that 5-HT1B receptors mediate the monosynaptic reflex depression induced by exogenously applied 5-HT that was formed from the precursor L-5-hydroxytryptophan in spinalized rats. In this study, we determined the effects of endogenous 5-HT, which was released from serotonergic terminals by DL-p-chloroamphetamine, on spinal reflexes.

Peritumoral CpG oligodeoxynucleotide treatment inhibits tumor growth and metastasis of B16F10 melanoma cells.

Although melanoma mostly affects the skin, it is notorious for its propensity to easily develop metastasis. Metastatic melanoma is highly resistant to a variety of therapies. We examined the anti-metastatic potential of peritumoral monotherapy against murine cutaneous B16F10 melanoma with synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs.

Antinociceptive effects of sodium channel-blocking agents on acute pain in mice.

The effects of various sodium channel blocking agents on acute thermal and mechanical nociception, as assessed using the plantar and tail pressure tests, respectively, were compared with the effects of morphine. The drugs used were mexiletine, lidocaine, carbamazepine, phenytoin, eperisone, tolperisone, and zonisamide. The sodium channel blocking agents exhibited a rather preferential elevation of the threshold for thermal nociception.

Noxious stimuli evoke a biphasic flexor reflex composed of A delta-fiber-mediated short-latency and C-fiber-mediated long-latency withdrawal movements in mice.

The nociceptive flexor reflex was studied in mice, focusing in particular on movement. Electrical stimuli delivered to the ventral aspect of the toe through a pair of needle electrodes inserted subcutaneously elicited a biphasic withdrawal reflex that was composed of short- and long-latency movements of the ipsilateral hind paw. The first response had a lower activation threshold compared with the second movement.

Endogenous GABA does not mediate the inhibitory effects of gabapentin on spinal reflexes in rats.

The novel antiepileptic drug gabapentin was designed as a structural analog of gamma-aminobutyric acid (GABA). However, its mechanism of action remains unclear. In the present study, we investigated the effect of gabapentin on spinal reflexes in anesthetized rats.

Serotonergic depression of spinal monosynaptic transmission is mediated by 5-HT1B receptors.

In the spinal cord, various subtypes of serotonin (5-hydroxytryptamine; 5-HT) receptors are involved in the modulation of motor output. Although the excitatory role of 5-HT(2) receptors is known, the receptor subtypes mediating the inhibitory effect of 5-HT on monosynaptic reflex transmission remain unclear. In this study, segmental spinal reflexes were recorded to examine the receptor subtypes underlying 5-HT-mediated inhibition of monosynaptic reflex transmission in spinalized rats.

Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal reflex transmission through 5-HT(2) receptors.

The centrally acting muscle relaxant cyclobenzaprine decreases the amplitude of monosynaptic reflex potentials by inhibiting the facilitatory descending serotonergic influences in the spinal cord. Interestingly, the structure of cyclobenzaprine is much similar to those of amitriptyline and cyproheptadine. In the present study, we attempted to elucidate the relationship between 5-HT(2) receptor antagonistic and inhibitory effects of cyclobenzaprine, amitriptyline, cyproheptadine and ketanserin on the spinal reflexes.