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J M Chung

Publications and source records attributed to J M Chung.

At least 19 recordsLinked to original sources
PubMed2000

Facilitation of NMDA-induced currents and Ca2+ transients in the rat substantia gelatinosa neurons after ligation of L5-L6 spinal nerves.

This study employing a rodent model of neuropathic pain investigated the influence of partial nerve injury on the ability of NMDA receptor activation to induce membrane currents and rises in cytosolic concentration of free calcium ([Ca2+]i) in the rat substantia gelatinosa (SG) neurons using simultaneous whole-cell patch-clamp recording and fura-2 calcium imaging in spinal slices. The novel findings are that: (I) L5-L6 spinal nerve ligation produces a sustained facilitation of NMDA-mediated membrane currents and [Ca2+]i rises both in the soma and dendrites of SG neurons on the injured side on post-operative days 4-13 after injury. (2) It appears that SG neurons in slices from injured rats recover from Ca2+ load less efficiently than neurons from naive rats. (3) The membrane depolarization-induced Ca2+ transients in SG neurons are not modified following spinal nerve ligation. The temporal profile of the changes in Ca2+ transients correlated well with the development of mechanical and thermal allodynia and hyperalgesia. These results suggest an important role of NMDA-mediated calcium signalling in the pathogenesis of neuropathic pain following spinal nerve injury.

Animals↗
PubMed2000

Potentiation of early necrotic death of glucose-starved pheochromocytoma 12 cells by nerve growth factor.

Recently suggested is an arguable hypothesis that neurotrophins can induce necrosis but suppress apoptosis of target cells in some pathological conditions. We examined this hypothesis by tracing the type of NGF-promoted cell death occurring in a hypoglycemic condition at various angles, such as kinetic analyses, histological examinations of membrane alterations, morphological observations in ultra-structural changes, and determinations of DNA fragmentation. Glucose-starved cell death consisted of two kinetically different stages, suggesting that it be mixed with early and delayed death. Several lines of evidence revealed that NGF prominently enhanced the early death with necrotic characters. By contrast, apoptotic characters of glucose-starved delayed death were not much affected by NGF. Nifedipine, a voltage-gated calcium channel blocker, could completely compensate for the enhancement of the early glucose-starved death by NGF. Interestingly, the NGF-promoted cell death was also blocked by cycloheximide that did not keep PC12 cells alive from glucose starvation. Therefore, all the data in this study suggest that NGF accelerates the early necrosis of glucose-starved cell death probably through the alterations of intracellular calcium ions and protein syntheses.

Animals↗
PubMed2000

Low dose of tetrodotoxin reduces neuropathic pain behaviors in an animal model.

We hypothesize that the accumulation of tetrodotoxin (TTX) sensitive sodium channels in injured dorsal root ganglion (DRG) neurons plays a critically important role in the generation of ectopic discharges and mechanical allodynia after peripheral nerve injury. Using the segmental spinal nerve (L5) ligation model of neuropathic pain, this hypothesis was tested by examining the effect of TTX on the mechanical sensitivity of the affected hind paw. Various concentrations of TTX were applied topically to the L5 DRG by using chronically implanted polyethylene tubing. The data showed that application of TTX at low doses (12.5-50 nM), which are far less than those needed for blocking action potential conduction, produced a significant elevation of mechanical threshold in the paw for foot withdrawals, a sign of reduced allodynic behaviors. The data suggest that TTX-sensitive subtypes of sodium channels play an important role in maintaining allodynic behaviors in an animal model of neuropathic pain.

Action Potentials↗
PubMed2000

Characteristics of ectopic discharges in a rat neuropathic pain model.

Injured afferent neurons produce spontaneous activity that is generated away from the normal impulse generation site. Since this activity, referred to as ectopic discharges, may play a significant role in neuropathic pain, it is important to systematically analyze the activity in various pain states. The present study used the segmental spinal nerve injury model of neuropathic pain to quantify the ectopic discharges from injured afferents in the neuropathic rat under various conditions. All aspects of measured ectopic discharges declined as postoperative time lengthened. Neuropathic pain behaviors declined in a similar fashion over the same time period. Surgical sympathectomy on neuropathic animals lowered the level of ectopic discharges along with neuropathic pain behaviors. The data indicate that the level of ectopic discharges is well correlated with that of pain behaviors in a rat neuropathic pain model, and this reinforces the supposition that ectopic discharges are important to the maintenance of neuropathic pain behaviors. The data suggest that there are two components of ectopic discharge generator mechanisms: sympathetically dependent and sympathetically independent components.

Action Potentials↗
PubMed2000

Spatial distribution of allozyme polymorphisms following clonal and sexual reproduction in populations of Rhus javanica (Anacardiaceae).

Rhus javanica L. (Anacardiaceae), a dioecious tree with both sexual reproduction and clonal growth, is widely distributed in warm temperate, subtropical, and tropical regions in east Asia. We used allozyme loci and spatial autocorrelation statistics to examine clonal structure and the spatial distribution of allozyme polymorphisms in two Korean populations. Populations of the species maintain moderate levels of allozyme variability (mean He=0.175, GST=0.060), and high levels of multilocus genotypic diversity (mean DG=0.971). Clone-pair distances ranged from 1.4 m to 57.4 m, and had high mean values of 24.0 m and 25.6 m in the two study populations. Approximate genetic patch widths were inferred to be 23-25 m. The results indicated that within populations there is moderate (one study population) or no (other study population) spatial genetic structure among sexually reproduced individuals, and vegetatively reproduced genotypes also are almost randomly distributed. The spatial genetic structure among sexually reproduced trees in the one case is probably caused by limited pollen dispersal in that population, and the lack of structure in the other probably results from the short time elapsed since founding. It appears that clonal reproduction also does not contribute substantially to genetic isolation by distance neither among the sexually reproduced individuals nor the total population. Ramets often establish long distances from their progenitors and thus do not substantially increase the degree of local consanguineous matings.

Genetic Markers↗
PubMed2000

Lack of pre-emptive analgesic effects of local anaesthetics on neuropathic pain.

We investigated the significance of pre-emptive analgesia using a well-known model of neuropathic pain in rats. Lignocaine, bupivacaine or saline was applied locally to the left L5-L6 spinal nerve before or 4 days after nerve injury. Mechanical allodynia was then evaluated before and after injury. Pre- and post-injury treatment with local anaesthetics both resulted in a two- to threefold increase in the pain threshold, as manifested by a significant increase in von Frey measurements. However, this effect lasted only 24 h. Our study in rats questions the beneficial effect of a single dose of local anaesthetic as pre-emptive analgesia.

Anesthetics, Local↗
PubMed1999

Ectopic discharges and adrenergic sensitivity of sensory neurons after spinal nerve injury.

At various times after spinal nerve injury, dorsal root ganglia (DRGs) from injured segments were removed with attached dorsal roots and spinal nerves. In an in vitro recording chamber, spontaneously active units were recorded from teased dorsal root fascicles. Sustained spontaneous activity could first be recorded at 13 h after the ligation, but adrenergic sensitivity did not develop until 24 h after the injury. Almost all recorded activity originated from the DRG. Thus, the DRG is the most common site for ectopic discharge generation after spinal nerve injury and separate mechanisms seem to be involved in the development of ectopic discharges and adrenergic sensitivity.

Action Potentials↗
PubMed1999

Electrophysiological evidence for the role of substance P in retinohypothalamic transmission in the rat.

The retinohypothalamic tract (RHT) is a neural pathway through which photic time cues are delivered directly to the mammalian circadian pacemaker in the suprachiasmatic nucleus (SCN). Although the excitatory amino acid glutamate is the primary neurotransmitter in the RHT, other substances such as substance P (SPq also have been suggested to play a role. The present study tested the hypothesis that SP participates in retinohypothalamic transmission and selectively modulates either N-methyl-D-aspartate (NMDA) or non-NMDA receptor-mediated neurotransmission. The SP antagonist L-703,606 depressed the excitatory postsynaptic current (EPSC) evoked by optic nerve stimulation in SCN neurons in rat hypothalamic slices. The SP antagonist also had a similar depressive effect on the NMDA and non-NMDA receptor-mediated components of the EPSC. These results suggest that SP is an excitatory neuromodulator contributing to the expression of both the NMDA and non-NMDA receptor-mediated components of retinohypothalamic transmission.

2-Amino-5-phosphonovalerate↗
PubMed1999

Expression of neurotrophin mRNAs in the dorsal root ganglion after spinal nerve injury.

Neurotrophins have specificity toward distinct subpopulations of dorsal root ganglion (DRG) neurons with different neurotrophin receptors. It has been suggested that neurotrophins also play important roles in mature DRG neurons after injury. In the present study, we examined the expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3) mRNAs in the DRG after a peripheral nerve injury. The data showed that following a spinal nerve ligation, the level of NGF mRNA increased 4 times over the normal level and was maintained at a high level for a period of 3 weeks. The induction of BDNF mRNA was brief (lasting less than 3 days) and lesser in quantity ( approximately 1. 7 times increase) compared to NGF expression. The expression of NT-3 mRNA was not detected either in normal or nerve injured rats. Results suggest that different neurotrophins play different functional roles in the DRG after spinal nerve injury.

Animals↗
PubMed1999

Changes in trkA expression in the dorsal root ganglion after peripheral nerve injury.

Most of the biological effects of nerve growth factor (NGF) are mediated by TrkA, the high affinity receptor for NGF. Previous studies have shown that NGF levels in the dorsal root ganglia (DRG) fluctuate following a peripheral nerve injury. The present study examined changes of TrkA immunoreactivity and trkA mRNA expression in the DRG after segmental nerve ligation. In the normal L5 DRG of the rat, there were, on average, 4700 TrkA-immunoreactive (TrkA-IR) neurons, representing 42% of the total neuronal population. Following L5 spinal nerve ligation, the number of TrkA-IR neurons in the L5 DRG slowly declined, reducing by 25% at 1 week and 35% at 3 weeks postoperation (PO). In contrast, trkA mRNA in these ganglia showed a significant decrease from 3 days to 3 weeks PO and was followed by a full recovery at 2 months PO. The early decrease of trkA mRNA is likely due to deprivation of target-derived NGF, which is caused by nerve ligation, and the recovery might be because substitute sources of NGF become available. Despite the decline in trkA mRNA in the ganglion, 3000 injured DRG neurons sustain TrkA immunoreactivity, suggesting that exogenous NGF can still influence these TrkA expressing neurons, even though they are isolated from the periphery. Accordingly, the effects of endogenous NGF should be as well manifested by local administration of NGF to the ganglion as to the stump of the damaged nerve.

Animals↗
PubMed1999

Different strains and substrains of rats show different levels of neuropathic pain behaviors.

This study compared and contrasted the manifestation of neuropathic pain behaviors in several strains of rats. These included ACI, Brown-Norway, Fischer 344, Lewis, Long-Evans, Sprague-Dawley, and Wistar-Furth, all obtained from Harlan Sprague-Dawley Inc. Comparison was also made between two substrains of Sprague-Dawley rats: one from Harlan and the other from Sasco. Neuropathic injury was produced by tightly ligating the left L5 and L6 spinal nerves with the animals under halothane anesthesia. Tests were conducted for 2 weeks to examine behavioral signs representing mechanical allodynia, cold allodynia, and spontaneous pain. There was no difference between strains in any of the tested behaviors before surgery. After neuropathic injury, rats in most groups developed high levels of behavioral signs of various components of neuropathic pain; however, some strains of rats showed weak behavioral signs of neuropathic pain. When a comparison was made between two substrains of Sprague-Dawley rats from two different sources, the ones from Sasco showed weaker behavioral signs than those from Harlan. When comparisons were made between different strains of rats from the same source (Harlan), Brown-Norway and Long-Evans rats showed the smallest magnitude of neuropathic pain behaviors. The data indicate that different strains and substrains of rats display different degrees of pain behaviors, suggesting that strains and substrains are important variables in the development of neuropathic pain after peripheral nerve injury.

Animals↗
PubMed1999

Heritability of nociception II. 'Types' of nociception revealed by genetic correlation analysis.

Clinical pain syndromes, and experimental assays of nociception, are differentially affected by manipulations such as drug administration and exposure to environmental stress. This suggests that there are different 'types' of pain. We exploited genetic differences among inbred strains of mice in an attempt to define these primary 'types'; that is, to identify the fundamental parameters of pain processing. Eleven randomly-chosen inbred mouse strains were tested for their basal sensitivity on 12 common measures of nociception. These measures provided for a range of different nociceptive dimensions including noxious stimulus modality, location, duration and etiology, among others. Since individual members of inbred strains are identical at all genetic loci, the observation of correlated strain means in any given pair of nociceptive assays is an index of genetic correlation between these assays, and hence an indication of common physiological mediation. Obtained correlation matrices were subjected to multivariate analyses to identify constellations of nociceptive assays with common genetic mediation. This analysis revealed three major clusters of nociception: (1) baseline thermal nociception, (2) spontaneously-emitted responses to chemical stimuli, and (3) baseline mechanical sensitivity and cutaneous hypersensitivity. Many other nociceptive parameters that might a priori have been considered closely related proved to be genetically divergent.

Animals↗
PubMed1999

Heritability of nociception I: responses of 11 inbred mouse strains on 12 measures of nociception.

It is generally acknowledged that humans display highly variable sensitivity to pain, including variable responses to identical injuries or pathologies. The possible contribution of genetic factors has, however, been largely overlooked. An emerging rodent literature documents the importance of genotype in mediating basal nociceptive sensitivity, in establishing a predisposition to neuropathic pain following neural injury, and in determining sensitivity to pharmacological agents and endogenous antinociception. One clear finding from these studies is that the effect of genotype is at least partially specific to the nociceptive assay being considered. In this report we begin to systematically describe and characterize genetic variability of nociception in a mammalian species, Mus musculus. We tested 11 readily-available inbred mouse strains (129/J, A/J, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, C58/J, CBA/J, DBA/2J, RIIIS/J and SM/J) using 12 common measures of nociception. These included assays for thermal nociception (hot plate, Hargreaves' test, tail withdrawal), mechanical nociception (von Frey filaments), chemical nociception (abdominal constriction, carrageenan, formalin), and neuropathic pain (autotomy, Chung model peripheral nerve injury). We demonstrate the existence of clear strain differences in each assay, with 1.2 to 54-fold ranges of sensitivity. All nociceptive assays display moderate-to-high heritability (h2 = 0.30-0.76) and mediation by a limited number of apparent genetic loci. Data comparing inbred strains have considerable utility as a tool for understanding the genetics of nociception, and a particular relevance to transgenic studies.

Animals↗
PubMed1999

Receptor subtype mediating the adrenergic sensitivity of pain behavior and ectopic discharges in neuropathic Lewis rats.

Receptor subtype mediating the adrenergic sensitivity of pain behavior and ectopic discharges in neuropathic Lewis rats. We attempted to identify the subtype of alpha-adrenergic receptor (alpha-AR) that is responsible for the sympathetic (adrenergic) dependency of neuropathic pain in the segmental spinal injury (SSI) model in the Lewis strain of rat. This model was chosen because our previous study showed that pain behaviors in this condition are particularly sensitive to systemic injection of phentolamine (PTL), a general alpha-AR blocker. We examined the effects of specific alpha1- and alpha2-AR blockers on 1) behavioral signs of mechanical allodynia, 2) ectopic discharges recorded in the in vivo condition, and 3) ectopic discharges recorded in an in vitro setup. One week after tight ligation of the L5 and L6 spinal nerves, mechanical thresholds of the paw for foot withdrawals were drastically lowered; we interpreted this change as a sign of mechanical allodynia. Signs of mechanical allodynia were significantly relieved by a systemic injection of PTL (a mixed alpha1- and alpha2-AR antagonist) or terazosin (TRZ, an alpha1-AR antagonist) but not by various alpha2-AR antagonists (idazoxan, rauwolscine, or yohimbine), suggesting that the alpha1-AR is in part the mediator of the signs of mechanical allodynia. Ongoing ectopic discharges were recorded from injured afferents in fascicles of the L5 dorsal root of the neuropathic rat with an in vivo recording setup. Ongoing discharge rate was significantly reduced after intraperitoneal injection of PTL or TRZ but not by idazoxan. In addition, by using an in vitro recording setup, spontaneous activity was recorded from teased dorsal root fibers in a segment in which the spinal nerve was previously ligated. Application of epinephrine to the perfusion bath enhanced ongoing discharges. This evoked activity was blocked by pretreatment with TRZ but not with idazoxan. This study demonstrated that both behavioral signs of mechanical allodynia and ectopic discharges of injured afferents in the Lewis neuropathic rat are in part mediated by mechanisms involving alpha1-ARs. These results suggest that the sympathetic dependency of neuropathic pain in the Lewis strain of the rat is mediated by the alpha1 subtype of AR.

Adrenergic alpha-Agonists↗
PubMed1999

Combined peripheral facial and abducens nerve palsy caused by caudal tegmental pontine infarction.

Isolated peripheral facial and abducens nerve palsy could theoretically be caused by a caudal pontine infarction, but as far as we know, there has been no published case history which has demonstrated this point. We describe the cases of two hypertensive patients who showed combined peripheral facial and abducens nerve palsy without other neurologic symptoms or signs. Other than hypertension, there was no identifiable etiology. Magnetic resonance imaging demonstrated compatible isolated ipsilateral ischemic infarction of the caudal tegmental pons. The present cases indicate that a well-placed small pontine infarction can cause isolated peripheral facial and abducens nerve palsy.

Abducens Nerve↗
PubMed1998

NGF-induced cytotoxicity in PC12 cells in a hypoglycemic environment.

Surprisingly, we observed that nerve growth factor (NGF) potentiated death of PC12 cells induced by glucose withdrawal, although NGF is widely believed to exert its protective role against several types of cell death. Since either glucose withdrawal or NGF treatment increases intracellular calcium levels of target cells in many cases, we hypothesized that further increase of intracellular calcium by NGF may be a determinant factor in the NGF-mediated cell death. To test this hypothesis, we examined the effect of NGF on cell death pharmacologically by measuring cell viability and traced the changes of intracellular calcium in various conditions using a confocal laser microscope. NGF promoted cell death under a glucose-deprived condition in a manner dependent on extracellular calcium, and nifedipine, but not ryanodine, could partially block the cell death. NGF treatment augmented further intracellular calcium that had been elevated by glucose withdrawal, the event that nifedipine could block. In this study, therefore, we tentatively concluded that NGF potentiates cell death of starved PC12 cells by accelerating the initial increase of intracellular calcium through activation of a dihydropyridine-sensitive calcium channel.

Animals↗
PubMed1998

Expression of nerve growth factor in the dorsal root ganglion after peripheral nerve injury.

Nerve growth factor (NGF) is believed to play a critical role in altering the phenotypic and functional properties of dorsal root ganglion (DRG) cells after a pathological insult. The present study examined NGF protein levels and NGF immunoreactivity (NGF-IR) in the DRG at multiple time points following peripheral nerve injury. The NGF protein level in the ipsilateral DRG decreased dramatically at 6 h after the injury, but recovered to an almost normal level at 2 days. In accordance with the NGF level, the proportion of NGF-IR neurons also showed a significant decrease at 6 h after the injury, but recovered to the normal level at 3 days. In addition, NGF-IR can also be found in satellite cells at a time point of 3 days after the injury. These data suggest that there is an increase in synthesis of NGF within the DRG after peripheral nerve injury, which contributes to the recovery of NGF levels. The newly synthesized NGF may play important roles in the reactions of DRG neurons to peripheral nerve injury.

Animals↗