Presynaptic NMDARs on spinal nociceptor terminals state-dependently modulate synaptic transmission and pain.

Postsynaptic NMDARs at spinal synapses are required for postsynaptic long-term potentiation and chronic pain. However, how presynaptic NMDARs (PreNMDARs) in spinal nociceptor terminals control presynaptic plasticity and pain hypersensitivity has remained unclear. Here we report that PreNMDARs in spinal nociceptor terminals modulate synaptic transmission in a nociceptive tone-dependent manner.

Characterization of Different Types of Excitability in Large Somatosensory Neurons and Its Plastic Changes in Pathological Pain States.

Sensory neuron types have been distinguished by distinct morphological and transcriptional characteristics. Excitability is the most fundamental functional feature of neurons. Mathematical models described by Hodgkin have revealed three types of neuronal excitability based on the relationship between firing frequency and applied current intensity.

Chronic cervical radiculopathic pain is associated with increased excitability and hyperpolarization-activated current ( I) in large-diameter dorsal root ganglion neurons.

Cervical radiculopathic pain is a very common symptom that may occur with cervical spondylosis. Mechanical allodynia is often associated with cervical radiculopathic pain and is inadequately treated with current therapies. However, the precise mechanisms underlying cervical radiculopathic pain-associated mechanical allodynia have remained elusive.

Gastrodin protects against chronic inflammatory pain by inhibiting spinal synaptic potentiation.

Tissue injury is known to produce inflammation and pain. Synaptic potentiation between peripheral nociceptors and spinal lamina I neurons has been proposed to serve as a trigger for chronic inflammatory pain. Gastrodin is a main bioactive constituent of the traditional Chinese herbal medicine Gastrodia elata Blume, which has been widely used as an analgesic since ancient times.

A Novel Nitronyl Nitroxide with Salicylic Acid Framework Attenuates Pain Hypersensitivity and Ectopic Neuronal Discharges in Radicular Low Back Pain.

Evidence has accumulated that reactive oxygen species and inflammation play crucial roles in the development of chronic pain, including radicular low back pain. Nonsteroid anti-inflammatory drugs (NSAIDs), for example, salicylic acid, aspirin, provided analgesic effects in various types of pain. However, long-term use of these drugs causes unwanted side effects, which limits their implication.

Α-Dendrotoxin-sensitive Kv1 channels contribute to conduction failure of polymodal nociceptive C-fibers from rat coccygeal nerve.

It is known that some patients with diabetic neuropathy are usually accompanied by abnormal painful sensations. Evidence has accumulated that diabetic neuropathic pain is associated with the hyperexcitability of peripheral nociceptors. Previously, we demonstrated that reduced conduction failure of polymodal nociceptive C-fibers and enhanced voltage-dependent sodium currents of small dorsal root ganglion (DRG) neurons contribute to diabetic hyperalgesia.

Upregulation of Ih expressed in IB4-negative Aδ nociceptive DRG neurons contributes to mechanical hypersensitivity associated with cervical radiculopathic pain.

Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron's ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear.

Electrophysiological Features of Neurons in the Mesencephalic Trigeminal Nuclei.

Mesencephalic trigeminal nucleus (Mes V) neurons represent an uncommon class of primary sensory neurons. Besides receiving somatosensory information, Mes V neurons are also involved in regulating multisensory information. The present review first describes the passive features as well as three important currents, followed by a distinct excitability classification and a description of the excitability transition of Mes V neurons.

Saikosaponin a mediates the anticonvulsant properties in the HNC models of AE and SE by inhibiting NMDA receptor current and persistent sodium current.

Epilepsy is one of the most common neurological disorders, yet its treatment remains unsatisfactory. Saikosaponin a (SSa), a triterpene saponin derived from Bupleurum chinensis DC., has been demonstrated to have significant antiepileptic activity in a variety of epilepsy models in vivo.

Dorsal root ganglion compression as an animal model of sciatica and low back pain.

As sciatica and low back pain are among the most common medical complaints, many studies have duplicated these conditions in animals. Chronic compression of the dorsal root ganglion (CCD) is one of these models. The surgery is simple: after exposing the L4/L5 intervertebral foramina, stainless steel rods are implanted unilaterally, one rod for each vertebra, to chronically compress the lumbar dorsal root ganglion (DRG).

Modulation of action potential trains in rabbit saphenous nerve unmyelinated fibers.

Usually, the main axon is assumed to faithfully conduct action potentials (APs). Recent data have indicated that neural processing can occur along the axonal path. However, the patterns and mechanisms of temporal coding are not clear.

Gastrodin inhibits allodynia and hyperalgesia in painful diabetic neuropathy rats by decreasing excitability of nociceptive primary sensory neurons.

Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients' quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive.

Presynaptically localized cyclic GMP-dependent protein kinase 1 is a key determinant of spinal synaptic potentiation and pain hypersensitivity.

Synaptic long-term potentiation (LTP) at spinal neurons directly communicating pain-specific inputs from the periphery to the brain has been proposed to serve as a trigger for pain hypersensitivity in pathological states. Previous studies have functionally implicated the NMDA receptor-NO pathway and the downstream second messenger, cGMP, in these processes. Because cGMP can broadly influence diverse ion-channels, kinases, and phosphodiesterases, pre- as well as post-synaptically, the precise identity of cGMP targets mediating spinal LTP, their mechanisms of action, and their locus in the spinal circuitry are still unclear.

Reduced conduction failure of the main axon of polymodal nociceptive C-fibres contributes to painful diabetic neuropathy in rats.

Painful diabetic neuropathy is a common complication of diabetes mellitus and can affect many aspects of life and severely limit patients' daily functions. Signals of painful diabetic neuropathy are believed to originate in the peripheral nervous system. However, its peripheral mechanism of hyperalgesia has remained elusive.

Evoked bursting in injured Aβ dorsal root ganglion neurons: a mechanism underlying tactile allodynia.

Chronic compression of rat dorsal root ganglion (CCD) produced tactile allodynia accompanied with hyperexcitability of the myelinated Aβ dorsal root ganglion (DRG) neurons. The Aβ DRG neuron hyperexcitability exhibits as bursting discharges in response to peripherally evoked action potentials (evoked bursting [EB]). The incidence of EB was significantly increased after chronic compression of DRG (CCD) (43.

Bilateral mechanical and thermal hyperalgesia and tactile allodynia after chronic compression of dorsal root ganglion in mice.

OBJECTIVE Low back pain is one of the most inextricable problems encountered in clinics. Animal models that imitate symptoms in humans are valuable tools for investigating low back pain mechanisms and the possible therapeutic applications. With the development of genetic technology in pain field, the possibility of mutating specific genes in mice has provided a potent tool for investigating the specific mechanisms of pain.

Blockade of persistent sodium currents contributes to the riluzole-induced inhibition of spontaneous activity and oscillations in injured DRG neurons.

In addition to a fast activating and immediately inactivating inward sodium current, many types of excitable cells possess a noninactivating or slowly inactivating component: the persistent sodium current (I(NaP)). The I(NaP) is found in normal primary sensory neurons where it is mediated by tetrodotoxin-sensitive sodium channels. The dorsal root ganglion (DRG) is the gateway for ectopic impulses that originate in pathological pain signals from the periphery.

Noise enhances subthreshold oscillations in injured primary sensory neurons.

Noise can play a constructive role in the detection of weak signals in various kinds of peripheral receptors and neurons. What the mechanism underlying the effect of noise is remains unclear. Here, the perforated patch-clamp technique was used on isolated cells from chronic compression of the dorsal root ganglion (DRG) model.

Behavioral assessments of the aversive quality of pain in animals.

Animals and humans share similar mechanisms of pain detection and similar brain areas involved in pain processing. Also, they show similar pain behaviors, such as reflexed sensation to nociceptive stimuli. Pain is often described in sensory discrimination (algosity) and affective motivation (unpleasantness) dimensions.

Ionic mechanisms of the effects of sleep deprivation on excitability in hippocampal pyramidal neurons.

It has been confirmed that sleep has a key role in learning and memory. Our previous study indicated that paradoxical sleep deprivation (PSD) impairs spatial learning ability of rats, and the decrease in membrane excitability of CA1 pyramidal neurons contributes to deficits in performing a spatial learning task. To investigate the further ionic mechanisms, the persistent sodium currents (I(NaP)), the hyperpolarization-activated cation current (I(h)), and their roles in neuron excitability were detected.

Research progress in transient receptor potential vanilloid 1 of sensory nervous system.

The transient receptor potential vanilloid subfamily member 1 (TRPV1) is a protein mainly expressed in sensory neurons and fibers, such as in trigeminal ganglion and dorsal root ganglion, and has been indicated to be involved in several physiological and pathological processes. Studies on thermal activation have revealed that phosphorylation is involved in TRPV1 activation and 2 putative phosphorylation sites, Ser residues 502 (Ser-502) and Ser residues 800 (Ser-800), have been recently confirmed to possess the capability of resensitizing TRPV1. In addition to acidification, alkalization has also been proved to be a highly effective stimulator for TRPV1.

Conduction failures in rabbit saphenous nerve unmyelinated fibers.

Recent experimental and theoretical data indicate that the functional capabilities of axons with specialized structures are much more diverse than traditionally thought. However, few observations were concerned with the main axons without arborization. In the present study, electrical stimulation of the saphenous nerve at different frequencies (2, 5, 10, 20 Hz) was used to test the role of activity-dependent effects on the pattern of action potentials that propagate along individual unmyelinated fibers (C fibers) within the trunk of the saphenous nerve in rabbits.

Gabapentin selectively reduces persistent sodium current in injured type-A dorsal root ganglion neurons.

It has been confirmed that the voltage-gated persistent sodium currents mediate the generation of subthreshold membrane potential oscillations (SMPOs) and contribute to shaping repetitive firing. Our previous study indicated that gabapentin (GBP) administration induced a dose-dependent inhibition of SMPO in chronically compressed dorsal root ganglion (CCD) neurons. To investigate the mechanisms and possible site(s) of action of GBP, the persistent sodium currents (I(NaP)) were measured and the effects of GBP on I(NaP) were examined in CCD neurons electrophysiologically in vitro.

[Analgesic effects of chemical lumbar sympathectomy on refractory pain in the lower limbs].

Objective: To evaluate the effect of chemical lumbar sympathectomy (CLS) on relieving refractory pain in the lower limbs.

Methods: Twenty-four patients with refractory pain in the lower limbs underwent CLS under X-ray guidance, and 2 ml contrast agent was injected at 1/3 of the second L2 vertebrae (the L2 sympathetic ganglion). Lidocaine was then injected followed by injection of 7% phenol for performing CLS.

Paradoxical sleep deprivation impairs spatial learning and affects membrane excitability and mitochondrial protein in the hippocampus.

Previous research has demonstrated that paradoxical sleep has a key role in learning and memory, and sleep deprivation interferes with learning and memory. However, the mechanism of memory impairment induced by sleep deprivation is poorly understood. The present study investigated the effect of paradoxical sleep deprivation (PSD) on spatial learning and memory using the Morris Water Maze.