• Molecules and Cells
• /
• v.20 no.3
• /
• pp.315-324
• /
• 2005

Pain is an unpleasant sensation experienced when tissues are damaged. Thus, pain sensation in some way protects body from imminent threat or injury. Peripheral sensory nerves innervated to peripheral tissues initially respond to multiple forms of noxious or strong stimuli, such as heat, mechanical and chemical stimuli. In response to these stimuli, electrical signals for conducting the nociceptive neural signals through axons are generated. These action potentials are then conveyed to specific areas in the spinal cord and in the brain. Sensory afferent fibers are heterogeneous in many aspects. For example, sensory nerves are classified as $A{\alpha}$, $-{\beta}$, $-{\delta}$ and C-fibers according to their diameter and degree of myelination. It is widely accepted that small sensory fibers tend to respond to vigorous or noxious stimuli and related to nociception. Thus these fibers are specifically called nociceptors. Most of nociceptors respond to noxious mechanical stimuli and heat. In addition, these sensory fibers also respond to chemical stimuli [Davis et al. (1993)] such as capsaicin. Thus, nociceptors are considered polymodal. Recent advance in research on ion channels in sensory neurons reveals molecular mechanisms underlying how various types of stimuli can be transduced to neural signals transmitted to the brain for pain perception. In particular, electrophysiological studies on ion channels characterize biophysical properties of ion channels in sensory neurons. Furthermore, molecular biology leads to identification of genetic structures as well as molecular properties of ion channels in sensory neurons. These ion channels are expressed in axon terminals as well as in cell soma. When these channels are activated, inward currents or outward currents are generated, which will lead to depolarization or hyperpolarization of the membrane causing increased or decreased excitability of sensory neurons. In order to depolarize the membrane of nerve terminals, either inward currents should be generated or outward currents should be inhibited. So far, many cationic channels that are responsible for the excitation of sensory neurons are introduced recently. Activation of these channels in sensory neurons is evidently critical to the generation of nociceptive signals. The main channels responsible for inward membrane currents in nociceptors are voltage-activated sodium and calcium channels, while outward current is carried mainly by potassium ions. In addition, activation of non-selective cation channels is also responsible for the excitation of sensory neurons. Thus, excitability of neurons can be controlled by regulating expression or by modulating activity of these channels.

• Applied Microscopy
• /
• v.28 no.4
• /
• pp.425-434
• /
• 1998

This study was designed to investigate the microglial reactions to the neurodegenerative changes in the cat retina. All experiments were performed using adult cats of both sex, weighing $2,500g\sim3,500g$. 5,7-DHT $(100{\mu}g)$ dissolved in 0.1% ascorbic acid was injected into the vitreous body. All injections were performed in one-side eye; the other side served as the control, which was injected only with 0.1% ascorbic acid. Cats were sacrificed at 1, 3, 7, 14 and 21 days after intravitreal injection of 5,7-DHT For light microscopy, retinae were fixed with 4% paraformaldehyde and processed using NDPase histochemistry. Same retinae were fixed with 1% para(formaldehyde-2.5% glutaraldehyde and processed for electron microscopy. NDPase-positive microglial cells were mainly distributed in the inner plexiform layer of the retina, and characterized by a small somata with a few slender processes, which were also extended in the ganglion cell layer (GCL) and inner nuclear layer (INL). The intensity of the microglia stained for NDPase was abruptly increased at 7 day as compared with that of the control, and thereafter continuously sustained until 21 day, the last experimental group in this study. Under the electron microscopical observation, microglial cells in the control group exhibited elongate nucleus with perinuclear chromatin condensation, and the perikaryon was scanty. However, a few hypertrophic glial cells were frequently found at 3 days after the drug injection. By 7 day, most microglial cells directed toward the degenerated neurons in the GCL, and the number of microglial cells was slightly increased as compared with the former group. At the 14 day, most microglial cells wrapped the degenerated cells in the GCL, and a few cells showed phagocytotic features. By 21 day, most microglial cells were engaged in phagocytotic activity, and their cytoplasm was filled with the phagorytosed material. Based on the results, 5,7-DHT may act as a specific neurotoxin to the cat retina, and microglial reactions to the neuronal death are already induced in early experimental stage. These results indicate that the microglial cells in the cat retina show characteristic features as a protective effect of neural tissue.

• Journal of The Korean Ophthalmological Society
• /
• v.59 no.11
• /
• pp.1097-1102
• /
• 2018

Purpose: To report a case of toxic optic neuropathy caused by chlorfenapyr ingestion accompanied by central nervous system involvement. Case summary: A 44-year-old female visited our clinic complaining of reduced visual acuity in both eyes for 7 days. She had ingested a mouthful of chlorfenapyr for a suicide attempt 2 weeks prior to the visit. Gastric lavage was performed immediately after ingestion at the other hospital. Her best-corrected visual acuity was finger count 30 cm in the right eye and hand motion in the left eye. Both pupils were dilated by 5.0 mm and the response to light was sluggish in both eyes. A relative afferent pupillary defect was detected in her left eye. Funduscopy revealed optic disc swelling in both eyes. Magnetic resonance imaging of the brain showed a symmetric hyper-intense signal in the white matter tract including the internal capsule, corpus callosum, middle cerebellar peduncle, and brainstem. The patient was diagnosed with toxic optic neuropathy induced by chlorfenapyr ingestion, and underwent high-dose intravenous corticosteroid pulse therapy. Three days later, the best-corrected visual acuity was no light perception in both eyes. Three months later, optic atrophy was observed in both eyes. Optical coherence tomography revealed a reduction in the thicknesses of the retinal nerve fiber layer and ganglion cell and inner plexiform layer in the macular area. Conclusions: Ingestion of even a small amount of chlorfenapyr can cause severe optic nerve damage through the latent period, despite prompt lavage and high-dose steroid treatment.

• Progress in Medical Physics
• /
• v.14 no.1
• /
• pp.54-67
• /
• 2003

The voltage-dependence of N-type calcium current inactivation is U-shaped with the degree of inactivation roughly mirroring inward current. This voltage-dependence has been reported to result from a purely voltage-dependent mechanism. However, $Ca^{2＋}$-dependent inactivation of N-channels has also been reported. We have investigated the role of $Ca^{2＋}$ in N-channel inactivation by comparing the effects of $Ba^{2＋}$and $Ca^{2＋}$ on whole-cell N-current in rat superior cervical ganglion neurons. For individual cells in-activation was always larger in $Ca^{2＋}$ than in $Ba^{2＋}$ even when internal EGTA (11 mM) was replaced with BAPTA (20 mM). The inactivation vs. voltage relationship was U-shaped in both divalent cations. The enhancement of inactivation by $Ca^{2＋}$ was inversely related with the magnitude of inactivation in $Ba^{2＋}$ as if the mechanisms of inactivation were the same in both $Ba^{2＋}$ and $Ca^{2＋}$. In support of this idea we could separate fast ( ${\gamma}$ ～150 ms) and slow ( ${\gamma}$ ～ 2500 ms) components of inactivation in both $Ba^{2＋}$and $Ca^{2＋}$ using 5 sec voltage steps. Differential effects were observed on each component with $Ca^{2＋}$ enhancing the magnitude of the fast component and the speed of the slow component. The larger amplitude of fast component indicates that the more channels inactivate via this pathway with $Ca^{2＋}$ than with $Ba^{2＋}$, but the stable time constants support the idea the fast inactivation mechanism is identical in $Ba^{2＋}$and $Ca^{2＋}$. The results do not support a $Ca^{2＋}$-dependent mechanism for fast inactivation. However, the $Ca^{2＋}$-induced acceleration of the slowly inactivating component could result from a $Ca^{2＋}$-dependent process.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.30 no.6
• /
• pp.465-473
• /
• 2004

Purpose : The essential triad for nerve regeneration is nerve conduit, supporting cell and neurotrophic factor. In order to improve the peripheral nerve regeneration, we used polyglycolic acid(PGA) tube and brain-derived neurotrophic factor(BDNF) gene transfected Schwann cells in sciatic nerve defects of SD rat. Materials and methods : Nerve conduits were made with PGA sheet and outer surface was coated with poly(lactic-co-glycolic acid) for mechanical strength and control the resorption rate. The diameter of conduit was 1.8mm and the length was 17mm Schwann cells were harvested from dorsal root ganglion(DRG) of SD rat aged 1 day. Schwann cells were cultured on the PGA sheet to test the biocompatibility adhesion of Schwann cell. Human BDNF gene was obtained from cDNA library and amplified using PCR. BDNF gene was inserted into E1 deleted region of adenovirus shuttle vector, pAACCMVpARS. BDNF-adenovirus was multiplied in 293 cells and purified. The BDNF-Adenovirus was then infected to the cultured Schwann cells. Left sciatic nerve of SD rat (250g weighing) was exposed and 14mm defects were made. After bridging the defect with PGA conduit, culture medium(MEM), Schwann cells or BDNF-Adenovirus infected Schwann cells were injected into the lumen of conduit, respectively. 12 weeks after operation, gait analysis for sciatic function index, electrophysiology and histomorphometry was performed. Results : Cultured Schwann cells were well adhered to PGA sheet. Sciatic index of BDNF transfected group was $-53.66{\pm}13.43$ which was the best among three groups. The threshold of compound action potential was between 800 to $1000{\mu}A$ in experimental groups which is about 10 times higher than normal sciatic nerve. Conduction velocity and peak voltage of action potential of BDNF group was the highest among experimental groups. The myelin thickness and axonal density of BDNF group was significantly greater than the other groups. Conclusion : BDNF gene transfected Schwann cells could regenerate the sciatic nerve gap(14mm) of rat successfully.