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J M Chung

Publications and source records attributed to J M Chung.

At least 55 records · Page 3Linked to original sources

Strain differences in adrenergic sensitivity of neuropathic pain behaviors in an experimental rat model.

The aim of this study was to examine and delineate the differences in adrenergic sensitivity of mechanical allodynic behavior among various strains of rats. Neuropathic injury was produced by tight ligation of the L5 and L6 spinal nerves in several strains of rats. The degree of mechanical allodynic behavior was estimated by measuring the mechanical threshold for paw flinching with von Frey filaments. Adrenergic sensitivity of the allodynic behavior was resolved by measuring changes of the mechanical threshold after intraperitoneal injection of phentolamine, an alpha-adrenergic receptor antagonist. Injection of phentolamine caused a significant but small increase in the thresholds for paw flinching in rats of most of the tested strains; however, in Lewis rats, the resulting threshold increase was extensive enough to eliminate allodynic behavior almost completely. It is concluded that there is a difference in adrenergic sensitivity to mechanical allodynic behavior among different strains of neuropathic rats. In particular, rats of the Lewis strain were extremely sensitive to systemic injection of an alpha-adrenergic receptor blocker.

Animals↗

Sprouting sympathetic fibers form synaptic varicosities in the dorsal root ganglion of the rat with neuropathic injury.

Peripheral nerve injury in a rat model (spinal nerve ligation) of neuropathic pain triggers sprouting of sympathetic fibers in the dorsal root ganglion (DRG). This sympathetic sprouting has been suggested as an important underlying mechanism for pain behaviors. To investigate the possibility of functional interaction between sprouted sympathetic fibers and sensory neurons, the present study examined the fine morphology and structural relationship between sympathetic fibers and the DRG neurons by electron microscopy. Sympathetic postganglionic fibers, as identified by electron microscopic immunostaining for tyrosine hydroxylase (TH), were all unmyelinated fibers and some of them ended as growth cones. In addition, many vesicle-containing axonal enlargements (we will refer these as synaptic varicosities) were found in the interstitial space around DRG neurons, and some were enclosed within the satellite cell capsule which surrounded the DRG soma. The presence of sympathetic synaptic varicosities near or in apposition with either the DRG somata or their processes provides a structural basis for possible interactions between sensory neurons and sympathetic fibers in the DRG of neuropathic rats.

Animals↗

Comparison of three rodent neuropathic pain models.

To characterize various animal models of neuropathic pain, we compared three previously developed rat models using the same behavioral testing methods. These models involve: (1) chronic constriction injury by loose ligation of the sciatic nerve (CCI); (2) tight ligation of the partial sciatic nerve (PSL); and (3) tight ligation of spinal nerves (SNL). Comparisons were made for the time course of behavioral signs representing various components of neuropathic pain as well as for the effects of surgical sympathectomy. In general, all three methods of peripheral nerve injury produced behavioral signs of both ongoing and evoked pain with similar time courses. However, there was a considerable difference in the magnitude of each pain component between models. Signs of mechanical allodynia were largest in the SNL injury and smallest in the CCI model. On the other hand, behavioral signs representing ongoing pain were much more prominent in the CCI model than in the other two. Although the behavioral signs of neuropathic pain tended to decrease after sympathectomy in all three models, the change was most evident in the SNL model. The results of the present study suggest that the three rat models tested have contrasting features, yet all are useful neuropathic pain models, possibly representing different populations of human neuropathic pain patients.

Animals↗

Loss of dorsal root ganglion cells concomitant with dorsal root axon sprouting following segmental nerve lesions.

Tight ligation of the fifth and sixth lumbar segmental nerves in the rat provides a model of neuropathic pain. We used this model to assess the changes in primary afferent input to the dorsal horn in neuropathic pain syndromes. Dorsal roots and ganglia were examined for up to 32 weeks following segmental nerve ligation. Stereologic and morphometric techniques revealed a notable decrease in the numbers of dorsal root ganglion cells and unmyelinated dorsal root axons by six weeks post-injury. By 32 weeks following segmental nerve ligations, the numbers of dorsal root ganglion cells have dropped to 50% of pre-ligation levels while the numbers of dorsal root axons have increased to normal levels predominantly due to sprouting of myelinated fibres. These findings indicate that although there is a great loss of dorsal root ganglion cells, there is dramatic sprouting of myelinated fibres and possibly some sprouting of unmyelinated fibres in the dorsal roots. Additionally, a difference in the responses of unmyelinated and myelinated fibres to this peripheral nerve injury is revealed. These changes in dorsal root ganglion cells and their central axons may underlie certain aspects of abnormal pain syndromes because of changes in the types and quantity of input the dorsal horn receives.

Animals↗

Sympathetic sprouting in the dorsal root ganglia of the injured peripheral nerve in a rat neuropathic pain model.

The extent of the sprouting of sympathetic postganglionic fibers in the dorsal root ganglion (DRG) and the peripheral nerves was examined in neuropathic rats at different postoperative times. After the L5 and L6 spinal nerves were ligated on one side, three different pain behavior tests (representing mechanical allodynia, cold allodynia, ongoing pain exacerbated by cold stress) were performed at various time intervals. The sympathetic postganglionic fibers were visualized by immunostaining with antibodies to tyrosine hydroxylase (TH). In the neuropathic rats, all three pain behaviors were fully developed within 3 days after the surgery, maintained up to 2 weeks, and then started to decline gradually afterward. At 20 weeks after neuropathic surgery, pain behaviors were reduced significantly compared to the peak response, but were still higher than the presurgery levels. Sympathectomy, performed 4 days after neuropathic surgery, almost completely abolished the signs of mechanical allodynia and ongoing pain behaviors, and it reduced the behaviors of cold allodynia to approximately half. The numerical density of sympathetic fibers in the DRG of an injured segment was significantly higher at 1, 4, and 20 weeks after neuropathic surgery as compared to the normal, suggesting that there is sprouting of sympathetic fibers in the DRG after peripheral nerve injury. Sprouting of sympathetic fibers in the DRG was extensive as early as 2 days after the spinal nerve ligation, and the sprouted fibers were almost completely eliminated after sympathectomy. The data suggest that sympathetic innervation of the DRG may play an important role in the development and maintenance of sympathetically maintained neuropathic pain.

Animals↗

Neuropathic pain in neonatal rats.

The aim of this study was to determine if peripheral nerve injury in neonatal rats triggers neuropathic pain behaviors as it does in adults. The injury was produced in three groups of neonatal rats (1, 2, and 3 weeks old) by tightly ligating the left L5 and L6 spinal nerves. Behavioral tests for mechanical allodynia were conducted from the 15th day after birth for the 1- and 2-week groups, and 1 day after surgery for the 3-week group. Rats in the 3-week group developed behaviors representing mechanical allodynia as is seen in adults. For the younger animals, however, the signs of mechanical allodynia lasted for a shorter period of time. These data suggest that a factor which is critically important for the maintenance of neuropathic pain develops between the 2nd and 3rd postnatal weeks.

Age Factors↗

Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case-control study in Pusan, Korea.

BACKGROUND: Liver cancer mortality in Korea is the highest in the world. Hepatitis B and C viruses (HBV, HCV) are known to be the major risk factors of hepatocellular carcinoma (HCC). Cholangiocarcinoma (CLG) accounts for more than 20% of liver cancer in the Pusan area. In Korea, the different roles of known risk factors in the development of HCC or CLG have not been adequately evaluated. METHODS: Case-control studies involved 203 incident HCC cases, 406 controls matched to the HCC cases for age (+/- 4 years) and sex, and 41 CLG cases (the HCC controls were used). They were carried out from August 1990 to August 1993. RESULTS: Relative risk (RR) of HBsAg (87.4; 95% confidence interval [CI]: 22.2-344.3) and RR of anti-HCV positivity (30.3; 95% CI: 6.1-150.6) were significant for the risk of HCC after adjustment for potentially confounding factors. In contrast, RR of Clonorchis sinensis in stool (2.7; 95% CI: 1.1-6.3) and RR of heavy drinking (4.6; 95% CI: 1.4-15.2) were significant for the risk of CLG. Transfusion history, acupuncture history, and cigarette smoking were not associated with the risk of HCC or CLG. CONCLUSIONS: Strong evidence indicated that both HBV and HCV infection were independent risk factors for HCC. In contrast, C. sinensis in stools and heavy drinking were associated with the risk of CLG in Korea.

Adult↗

Effects of age on behavioral signs of neuropathic pain in an experimental rat model.

The present study examined the effect that aging has on the manifestations of pain behaviors in a rat model of neuropathic pain. Two experiments were conducted. The first experiment compared young, mature and old rats. After tight ligation of the L5 and L6 segmental spinal nerves, young rats displayed much more vigorous behavioral signs of mechanical allodynia and ongoing pain than did either mature or old rats. The second experiment was done using the same rats at two different time points. Spinal nerve ligation was done on the left side of rats when they were young and the same surgery was repeated on the right side 20 weeks later (mature age). Comparison of pain behaviors between the left and right sides confirmed the results of the first experiment. The data suggest that younger rats show much more robust behavioral signs of neuropathic pain compared to older rats.

Aging↗

Reliability of computer-generated prediction tracing.

The reliability of a commercially available computer prediction program (Quick Ceph II) was evaluated using pretreatment and posttreatment cephalograms of 30 patients who were treated during an active period of growth. The computer prediction was compared with the actual treatment result, and the growth forecast with the computer program was compared with the growth forecast using a manual method. Using paired student's t-tests, predictions for 5 of the 10 variables measured were found to be statistically reliable. Comparing the relative accuracy of growth prediction in terms of absolute values, the computer came closer to the actual result in four of the nine variables, while the manual method came closer in three variables. Predictions for the other two variables were virtually the same using both methods. The manual method of prediction was sufficient to give a reasonably good graphic representation of growth changes to create a VTO. However, the computer offers the added advantages of quicker access to information and somewhat greater accuracy in producing the tracing, as well as its use in patient education.

Adolescent↗

Increased nitric oxide synthase immunoreactivity in rat dorsal root ganglia in a neuropathic pain model.

In rats, tight ligation of L5 and L6 spinal nerves produces symptoms of thermal hyperalgesia and mechanical allodynia, mimicking the symptoms which characterise painful peripheral neuropathies in humans. Immunoreactivity for nitric oxide synthase (NOS) was investigated in lumbar (L1, L4, L5 and L6) dorsal root ganglia from naive controls and from rats surviving for 3, 7, and 14 days after unilateral ligation of the L5 and L6 spinal nerves. Quantitative analysis revealed significant increases in the percentage of NOS-immunoreactive cell profiles in L5 and L6 ganglia on the operated side at all time points, with the number of labelled profiles increasing with time following ligation, but L1 and L4 ganglia were unaffected. These findings suggest that nitric oxide may have a role in the generation and/or maintenance of neuropathic pain.

Amino Acid Oxidoreductases↗

Immunohistochemical evidence for sprouting of ventral root afferents after neonatal sciatic neurectomy in the rat.

The present study demonstrates that afferent fibers in the rat ventral root sprout after transection of the neonatal sciatic nerve. The key data are that the number of unmyelinated fibers increased dramatically in the L5 ventral roots and about half of these unmyelinated fibers were labeled with antibody to growth associated phosphoprotein (GAP-43), suggesting that they are regenerating axons. Furthermore, these fibers survived in the distal stump of the acutely cut ventral root, suggesting that they are afferent fibers. The results provide direct evidence for sprouting of afferent fibers in the ventral root induced by a neonatal peripheral nerve lesion.

Animals↗

Quantitative assessment of tactile allodynia in the rat paw.

We applied and validated a quantitative allodynia assessment technique, using a recently developed rat surgical neuropathy model wherein nocifensive behaviors are evoked by light touch to the paw. Employing von Frey hairs from 0.41 to 15.1 g, we first characterized the percent response at each stimulus intensity. A smooth log-linear relationship was observed, with a median 50% threshold at 1.97 g (95% confidence limits, 1.12-3.57 g). Subsequently, we applied a paradigm using stimulus oscillation around the response threshold, which allowed more rapid, efficient measurements. Median 50% threshold by this up-down method was 2.4 g (1.81-2.76). Correlation coefficient between the two methods was 0.91. In neuropathic rats, good intra- and inter-observer reproducibility was found for the up-down paradigm; some variability was seen in normal rats, attributable to extensive testing. Thresholds in a sizable group of neuropathic rats showed insignificant variability over 20 days. After 50 days, 61% still met strict neuropathy criteria, using survival analysis. Threshold measurement using the up-down paradigm, in combination with the neuropathic pain model, represents a powerful tool for analyzing the effects of manipulations of the neuropathic pain state.

Animals↗

Grouping of somatosensory neurons in the spinal cord and the gracile nucleus of the rat by cluster analysis.

1. A set of 11 cutaneous stimuli defined previously to differentiate among different types of cutaneous sensory receptors in the rat hindpaw was also effective in differentially activating second-order sensory neurons in the dorsal horn and the gracile nucleus of rats. 2. All sampled units were responsive to more than 1 of the 11 stimuli. However, none responded to innocuous warming or cooling stimuli. Therefore further analysis was restricted to responses to nine of the selected stimuli. 3. Cluster analysis of the responses to nine selected innocuous and noxious mechanical stimuli and noxious thermal stimuli yielded seven classes that seemed functionally distinct from each other: a class of high-threshold neurons, three classes of convergent (wide dynamic range) neurons, a class of a mixture of poorly responsive neurons and neurons receiving Pacinian inputs, and two classes of low-threshold neurons. 4. High-threshold neurons responded predominantly to noxious mechanical and thermal stimuli and presumably received an input from both mechanically and thermally sensitive nociceptors. These cells were located in the dorsal horn, and some were spinothalamic tract cells. Wide dynamic range neurons were excited by innocuous and noxious stimuli, but better by noxious stimuli. These classes of cells were either in the dorsal horn (some were spinothalamic tract cells) or in the nucleus gracilis.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Neonatal sciatic nerve lesion triggers the sprouting of fibers in the contralateral ventral root of the rat.

We explored the possibility that unilateral neurectomy of the sciatic nerve of the rat at the neonatal stage triggers sprouting of afferent fibers in the contralateral ventral root. 3 months after neonatal sciatic neurectomy, the numbers of both myelinated and unmyelinated fibers in the L5 and L3 ventral roots were counted on electron micrographic montages. Age-matched littermates were used as unoperated controls. To identify regenerating axons, electron microscopic immunohistochemistry was done on the ventral roots using antibody against growth-associated phosphoprotein (GAP-43). Neonatal sciatic neurectomy resulted in: (1) about a three-fold increase in the number of unmyelinated fibers in the contralateral L5 ventral root as compared with the unoperated control; (2) about a 25-fold increase in the number of unmyelinated fibers in the ipsilateral L5 ventral root as compared with the control; (3) approximately 25% of the unmyelinated fibers in the contralateral L5 ventral root expressing GAP-43; and (4) no significant change in the number of unmyelinated fibers in the L3 ventral root of either side as compared with the control. The data suggest that a neonatal sciatic neurectomy of the rat triggers sprouting of unmyelinated afferent fibers in the ventral root of the contralateral as well as the ipsilateral side. The sprouting is restricted, however, to spinal segments which receive inputs from the sciatic nerve.

Animals↗

Abnormalities of sympathetic innervation in the area of an injured peripheral nerve in a rat model of neuropathic pain.

Using the rat model that we have developed, a potential underlying mechanism for sympathetically maintained neuropathic pain (SMP) was explored. In rats showing neuropathic pain behaviors after a tight ligation of the L5 spinal nerve, putative sympathetic postganglionic fibers were examined in the injured spinal nerve and the dorsal root ganglion (DRG), using immunohistochemical staining with antibody against tyrosine hydroxylase (TH). In the neuropathic rats, there was an increase in the number of TH-immunolabeled fibers in the spinal nerve, and some DRG cells were surrounded by the labeled fibers. These abnormalities of sympathetic postganglionic innervation of the injured spinal nerve or the DRG may be a part of the mechanisms underlying the development of SMP.

Animals↗

Response properties of hypogastric afferent fibers supplying the uterus in the cat.

The present study was undertaken to examine the sensory function of uterine afferent fibers in cats at unknown stages of the estrous cycle. Single unit activity was recorded from strands of the hypogastric nerve of the anesthetized cat. Once a unit was found, the conduction velocity was determined and the mechanical receptive field localized on the uterus. The response properties of the unit to mechanical stimuli applied to the receptive field and to chemical stimuli applied by intra-arterial injection of algesic chemicals (bradykinin, KCl and capsaicin) into the uterine artery were studied. Single unit activity from a total of 52 units was examined in this study. Based on the conduction velocities, about 2/3 of these fibers were found to be unmyelinated C fibers and the remaining 1/3 were thinly myelinated A delta fibers. The receptive fields of most of these fibers were located at different parts of the uterine horn and body while a few were at the uterine cervix. Mechanical thresholds, as determined by von Frey filaments applied to the external surface of the uterus, varied more than 150-fold among mechanically sensitive units, ranging from extremely low to high thresholds. In addition, most of these afferents were activated by intra-arterially injected algesic chemicals, often by more than one chemical. The data in the present study suggest that a large portion of the cat uterus is innervated by the hypogastric nerve and that these afferents originate from sensory receptors that have potentially a wide range of functions. Their potential functions as low threshold mechanoreceptors and nociceptors are discussed.

Afferent Pathways↗

Signs of neuropathic pain depend on signals from injured nerve fibers in a rat model.

The present study was undertaken to determine the role of injured fibers in the development of neuropathic pain using our earlier established rat model. Our model was produced by placing tight ligatures to the L5 or both the L5 and L6 spinal nerves on one side in the rat. These rats showed long-lasting behavioral signs of mechanical allodynia and heat hyperalgesia. Using the uniqueness of our model, 3 specific questions are being asked concerning the initiation and maintenance of behavioral signs for neuropathic pain. The results of behavioral tests performed after various surgical manipulations suggest that: (1) peripheral nerve injury itself is the critical factor for the development of behavioral signs of neuropathic pain; (2) signs of neuropathic pain appear only when injury occurs at a part of the peripheral nerve distal to the dorsal root ganglion; and (3) signals (either electrical or chemical) entering the spinal cord from the injured fibers or the dorsal root ganglion cells play a critical role for both initiation and maintenance of the neuropathic pain state.

Animals↗