• International Journal of Oral Biology
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• v.45 no.4
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• pp.225-231
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• 2020

Glial cells, including astrocytes and microglia, interact closely with neurons and modulate pain transmission, particularly under pathological conditions. In this study, we examined the excitability of substantia gelatinosa (SG) neurons of the spinal dorsal horn using a patch clamp recording to investigate the roles of microglial activation in the nociceptive processes of rats. We used xanthine/xanthine oxidase (X/XO), a generator of superoxide anion (O2·-), to induce a pathological pain condition. X/XO treatment induced an inward current and membrane depolarization. The inward current was significantly inhibited by minocycline, a microglial inhibitor, and fluorocitrate, an astrocyte inhibitor. To examine whether toll-like receptor 4 (TLR4) in microglia was involved in the inward current, we used lipopolysaccharide (LPS), a highly specific TLR4 agonist. The LPS induced inward current, which was decreased by pretreatment with Tak-242, a TLR4-specific inhibitor, and phenyl N-t-butylnitrone, a reactive oxygen species scavenger. The X/XO-induced inward current was also inhibited by pretreatment with Tak-242. These results indicate that the X/XO-induced inward current of SG neurons occurs through activation of TLR4 in microglial cells, suggesting that neuroglial cells modulate the nociceptive process through central sensitization.

• The Korean Journal of Pain
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• v.35 no.2
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• pp.152-159
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• 2022

Background: Subjects with frozen shoulder (FS) might not be comfortable with vigorous physical therapy. Clinical trials assessing the effect of graded motor imagery (GMI) in FS are lacking. The aim of this study was to determine the effect of GMI as an adjunct to conventional physiotherapy in individuals with painful FS. Methods: Twenty subjects aged 40-65 years having stage I and II of FS were randomly divided into two study groups. The conventional physiotherapy group (n = 10) received electrotherapy and exercises while the GMI group (n = 10) received GMI along with the conventional physiotherapy thrice a week for 3 weeks. Pre- (Session 1) and post- (Session 9) intervention analysis for flexion, abduction, and external rotation range of motion (ROM) using a universal goniometer, fear of movement using the fear avoidance belief questionnaire (FABQ), pain with the visual analogue scale, and functional disability using the shoulder pain and disability index (SPADI) was done by a blinded assessor. Results: Statistically significant difference was seen within both the groups for all the outcomes. In terms of increasing abduction ROM as well as reducing fear of movement, pain, and functional disability, the GMI group was significantly better than control group. However, both groups were equally effective for improving flexion and external rotation ROM. Conclusions: Addition of GMI to the conventional physiotherapy proved to be superior to conventional physiotherapy alone in terms of reducing pain, kinesiophobia, and improving shoulder function for stage I and II of FS.

• International Journal of Oral Biology
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• v.33 no.3
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• pp.117-123
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• 2008

Reactive oxygen species (ROS) are toxic agents that may be involved in various neurodegenerative diseases. Recent studies indicate that ROS can act as modulators of neuronal activity, and are critically involved in persistent pain primarily through spinal mechanisms. In the present study, whole cell patch clamp recordings were carried out to investigate the effects of tert-buthyl hydroperoxide (t-BuOOH), an ROS, on neuronal excitability and the mechanisms underlying changes of membrane excitability. In current clamp condition, application of t-BuOOH caused a reversible membrane depolarization and firing activity in substantia gelatinosa (SG) neurons. When slices were pretreated with phenyl-N-tert-buthylnitrone (PBN) and ascorbate, ROS scavengers, t-BuOOH failed to induce membrane depolarization. However, isoascorbate did not prevent t-BuOOH-induced depolarization, suggesting that the site of ROS action is intracellular. The t-BuOOH-induced depolarization was not blocked by pretreatment with dithiothreitol (DTT), a sulfhydryl-reducing agent. The membrane-impermeant thiol oxidant 5,5-dithiobis 2-nitrobenzoic acid (DTNB) failed to induce membrane depolarization, suggesting that the changes of neuronal excitability by t-BuOOH are not caused by the modification of extrathiol group. The t-BuOOH-induced depolarization was suppressed by the phospholipase C (PLC) blocker U-73122 and inositol triphosphate ($IP_3$) receptor antagonist 2-aminoethoxydiphenylbolate (APB), and after depletion of intracellular $Ca^{2+}$ pool by thapsigargin. These data suggest that ROS generated by peripheral nerve injury can induce central sensitization in spinal cord, and t-BuOOH-induced depolarization may be regulated by intracellular $Ca^{2+}$ store mainly via $PLC-IP_3$ pathway.

• International Journal of Oral Biology
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• v.38 no.1
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• pp.5-12
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• 2013

Recent studies indicate that reactive oxygen species (ROS) can act as modulators of neuronal activity, and are critically involved in persistent pain primarily through spinal mechanisms. In this study, we investigated the effects of NaOCl, a ROS donor, on neuronal excitability and the intracellular calcium concentration ($[Ca^{2+}]_i$) in spinal substantia gelatinosa (SG) neurons. In current clamp conditions, the application of NaOCl caused a membrane depolarization, which was inhibited by pretreatment with phenyl-N-tert-buthylnitrone (PBN), a ROS scavenger. The NaOCl-induced depolarization was not blocked however by pretreatment with dithiothreitol, a sulfhydryl-reducing agent. Confocal scanning laser microscopy was used to confirm whether NaOCl increases the intracellular ROS level. ROS-induced fluorescence intensity was found to be increased during perfusion of NaOCl after the loading of 2',7'-dichlorofluorescin diacetate ($H_2DCF$-DA). NaOCl-induced depolarization was not blocked by pretreatment with external $Ca^{2+}$ free solution or by the addition of nifedifine. However, when slices were pretreated with the $Ca^{2+}$ ATPase inhibitor thapsigargin, NaOCl failed to induce membrane depolarization. In a calcium imaging technique using the $Ca^{2+}$-sensitive fluorescence dye fura-2, the $[Ca^{2+}]_i$ was found to be increased by NaOCl. These results indicate that NaOCl activates the excitability of SG neurons via the modulation of the intracellular calcium concentration, and suggest that ROS induces nociception through a central sensitization.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.2
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• pp.432-437
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• 2007

Reactive oxygen species (ROS) are toxic agents that may be involved in various neurodegenerative diseases. Recent studies indicate that ROS are also involved in persistent pain through a spinal mechanism. In the present study, whole cell patch clamp recordings were carried out on substantia gelatinosa (SG) neurons in spinal cord slice of neonatal rats to investigate the effects of ROS on neuronal excitability and excitatory synaptic transmission. In current clamp condition, tert-buthyl hydroperoxide (t-BuOOH), an ROS donor, induced a electrical hyperexcitability during t-BuOOH wash-out followed by a brief inhibition of excitability in SG neurons. Application of t-BuOOH depolarized membrane potential of SG neurons and increased the neuronal firing frequencies evoked by depolarizing current pulses. Phenyl-N-tert-buthylnitrone (PBN), an ROS scavenger, antagonized t-BuOOH induced hyperexcitability. IN voltage clamp conditions, t-BuOOH increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). In order to determine the site of action of t-BuOOH, miniature excitatory postsynaptic currents (mEPSCs) were recorded. t-BuOOH increased the frequency and amplitude of mEPSCs, indicating that it may modulate the excitability of the SG neurons via pre- and postsynaptic actions. These data suggest that ROS generated by peripheral nerve injury can induce central sensitization in spinal cord.

• The Korean Journal of Pain
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• v.12 no.1
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• pp.21-26
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• 1999

Background: Preoperative blocking of surgical nociceptive inputs may prevent sensitization of central nervous system (CNS) and reduce postoperative pain. The stress responses to surgical trauma consist of increase in catabolic hormones and decrease in anabolic hormones. We studied whether preoperative low dose epidural bupivacaine and morphine could affect postoperative pain, changes plasma cortisol, and serum glucose. Methods: Thirty patients undergoing total abdominal hysterectomy were randomly assigned to one of three groups. General anesthesia was induced in all patients and after that, epidural blocks were done except the control group (n=10) patients. Preoperative block group (n=10) received 0.5% bupivacaine 50 mg and morphine 2 mg epidurally as a bolus before operation and followed by 0.1% bupivacaine $5\;mghr^{-1}$ and morphine $0.2\;mghr^{-1}$ for 10 hours. Postoperative block group (n=10) received the same doses of bupivacaine and morphine under the same method postoperatively. Postoperative pain relief was provided with i.v. fentanyl through Patient-Controlled-Analgesia Pump. Postoperative pain by visual analogue scores (VAS), analgesic requirement (first requirement time, total amounts used), side effects, plasma cortisol level and serum glucose level were compared. Results: Until postoperative 6 hrs, VAS of control group was higher than those of the epidural groups. No difference was observed in VAS between the two epidural groups. First analgesics requirement time and total amounts of used analgesics were not different between the two epidural groups, but first analgesic requirement time of preoperative block group was significantly prolonged compared with control group. Plasma cortisol and serum glucose levels were not different among groups. Conclusions: Low dose preoperative epidural bupivacaine and morphine could not reduce postoperative pain, plasma cortisol level and serum glucose level compared with postoperative block group.

• Corrosion Science and Technology
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• v.13 no.3
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• pp.112-119
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• 2014

In this work, it is aimed to develop the fabrication method of axial stress corrosion cracking (SCC) defects having various sizes, on the outer diameter surface of the steam generator (SG) tubings. To control the length of the artificial SCC defect, the specific area of the SG tubing samples was exposed to an acidic solution after a sensitization heat treatment. During the exposure to an acidic solution, a direct current potential drop (DCPD) method was adopted to monitor the crack depth. The size of the SCC defect was first evaluated by an eddy current test (ECT), and then confirmed by a destructive examination. From the comparison, it was found that the actual crack length was well controlled to be similar to the length of the surface exposed to an acidic solution (5, 10, 20 or 30 mm in this work) with small standard deviation. From in-situ monitoring of the crack depth using the DCPD method, it was possible to distinguish a non-through wall crack from a through wall crack, even though the depth of the non-through wall crack was not able to be precisely controlled. The fabrication method established in this work was useful to simulate the SCC defect having similar size and ECT signals as compared to the field cracks in the SG tubings of the operating Korean PWRs.

• Journal of Dental Anesthesia and Pain Medicine
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• v.20 no.3
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• pp.147-154
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• 2020

Background: Single inferior alveolar nerve block is ineffective in achieving adequate pulpal anesthesia in 30-80% of patients due to anatomical variations, local tissue pH, central sensitization, and several factors. Various supplementary techniques and combination of adjuvants with lignocaine are used to overcome these failures. Magnesium sulfate (MgSO₄), one such adjuvant, acts at the N-methyl-D-aspartate glutamate receptor resulting in effective anesthesia. The aim of this prospective, randomized, double-blind, clinical controlled trial was to evaluate the onset, anesthetic efficacy, duration and post-operative analgesia of 2% lignocaine with and without the addition of MgSO₄ in patients with symptomatic irreversible pulpitis and apical periodontitis. Methods: Fourty-two patients were randomly divided into three groups: 2% lignocaine (group 1) and 2% lignocaine with MgSO₄ (75 mg) and (150 mg) in groups 2 and 3, respectively. Pre-operative vitals and Heft Parker-Visual Analogue Scale (HP-VAS) pain scores were recorded. The onset of anesthesia, anesthetic efficacy, and duration of anesthesia were evaluated post administration of the local anesthetic solution. The post-operative analgesia was examined at intervals of 2, 6, 12, 24, and 48 h. Results: Administration of 150 mg MgSO₄ hastens the onset of anesthesia (1.29 min) and produces better anesthetic efficacy (3.29 HP-VAS) compared to group 2 (2.07 min and 9.14 HP-VAS) and group 1 (3.29 min and 35.79 HP-VAS), respectively. The duration of anesthesia was significantly higher in group 3 (247.07 min) compared to that of groups 2 and 1 (190 min and 110.21 min) with P < 0.05. Conclusion: Combining 75 mg or 150 mg of MgSO₄ with lignocaine is more effective than 2% lignocaine and 75 mg of MgSO₄ is adequate for endodontic procedures.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.8_spc
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• pp.1266-1274
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• 2019

This paper presents a review of dairy goat production in sub-Saharan Africa (SSA) from 2010- 2017, its current state, constraints and prospects for research and development. Since the introduction of dairy goats in SSA in pre-colonial times, their populations have continued to increase due to declining land size as a result of land fragmentation and increasing demand for goat milk. The current goat population in SSA is 372,716,040 head of which only 15.98% used for milk production. Populations in the Eastern and Western regions of SSA have shown an increasing trend from 2010 to 2017. The Southern Africa goat population is on the decline at an annual rate of about 1.77% whereas Central Africa has had a constant goat population within the same period. Eastern Africa reported the highest increase in the population of goats used for milk production. Milk production was highest in Eastern Africa and lowest in Southern Africa. However, dairy goat productivity remained constant in the Eastern region throughout the review period. Dairy goats are mainly raised under smallholder mixed crop-livestock systems. To enhance the development of the dairy goat, concerted efforts should be made to alleviate the constraints that stifle its growth. These constraints can be categorized into nutrition and feeding, breeding and reproduction, diseases, parasites, climate change, and underdeveloped dairy goat products market. Effective management of dairy goats requires a holistic approach and there is the need to expand the markets by further sensitization on the nutritional and medicinal advantages of dairy goat products. In order to achieve rapid development in the dairy goat sub sector, research and development initiatives should be directed towards alleviating the hurdles in nutrition and feeding, breeding, animal health and resilience as well as dairy goat markets.

• Physical Therapy Rehabilitation Science
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• v.8 no.1
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• pp.15-21
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• 2019

Objective: The purpose of this study was to identify whether cutaneous sensory (CS) changes induced by mechanical intervention (MI) increases the trigger point threshold of the same spinal segment as well as to investigate the relationship between the amounts of change in CS pressure pain thresholds (PPT). Design: Randomized controlled trial. Methods: Thirty-nine persons with myofacial pain (MFP) were recruited in this experiment. The subjects consisted of 20 men and 19 women (age 20-39). MI was applied on the subjects using the Graston technique for 5 minutes to induce CS changes. The CS changes were measured with sensory tests by using the Von Frey Filament, and PPT changes were estimated by using the pressure threshold meter. For the observation of sensory and PPT changes with time, the test was conducted for 15 minutes including a pre, post, and after intervention session. Results: CS threshold increased significantly when MI was applied (p<0.001). On the same spinal segment, changes in the right infraspinatus PPT was observed (p<0.001) but the PPT changes in other muscles were not significantly different. Furthermore, the control group CS and PPT were not significantly different. In addition, regression analysis showed that the CS changes have a larger impact on PPT in the same spinal segment (p<0.001). Conclusions: CS changes induced by MI make to change PPT on the same spinal segment. In other words, it is possible to identify PPT changes following CS changes except for the muscle which belongs to a different spinal segment. Therefore, application of MI is necessary for the CS changes in the same spinal segment. Furthermore, it can be useful in the clinical fields as a method of providing pain control and increasing the PPT.