• Restorative Dentistry and Endodontics
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• v.45 no.3
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• pp.40.1-40.12
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• 2020

Objectives: The aim of this study was to evaluate the effects of endodontic treatment on levels of substance P (SP) and calcitonin gene-related peptide (CGRP) in the saliva of patients with symptomatic apical periodontitis. Materials and Methods: Twelve patients with mandibular molars with symptomatic apical periodontitis were enrolled in this study. An initial saliva sample was collected just before administration of anesthesia for root canal treatment, which was performed at the first visit. A second saliva sample was collected at a control visit 1 week after treatment. Salivary SP and CGRP levels were evaluated quantitatively using biochemical assays. The data were analyzed using Pearson correlation analysis, the paired samples t-test, and the Mann-Whitney U test (p = 0.05). Results: The postoperative salivary level of SP was significantly lower than the preoperative level (p = 0.005). However, the postoperative salivary level of CGRP was similar to the preoperative level (p = 0.932). Visual analog scale (VAS) scores of patients' subjective pain were found to be positively correlated with salivary levels of SP (r = 0.421; p = 0.040). No statistically significant correlations were observed between salivary levels of CGRP and VAS scores for patients' subjective percussion tenderness (p = 0.533) or VAS scores for patients' subjective pain (p = 0.459). Conclusions: According to the results of the present study, salivary SP levels may be used as an objective indicator in the diagnosis and assessment of the degree of pain in endodontic diseases.

• Restorative Dentistry and Endodontics
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• v.31 no.3
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• pp.153-160
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• 2006

We investigated the secretion of Interleukin-8 (IL-8) from ginviva and periodontal ligament stimulated with Substance P (SP) and Calcitonin Gene-related Peptide (CGRP). Gingiva (GF), periodontal ligament (PDLF) and pu)p (PF) tissues were collected from extracted intact 3rd molars. Cultured cells were stimulated with different concentrations of SP for 4 hrs, and stimulated with SP, CGRP and Tumor Necrosis Factor-$\alpha$ (TNF-$\alpha$) for 8 hrs. Then RNase Protection Assay was carried out. ELISA was performed using supernatants of stimulated cells for quantitative analysis of IL-8. Results were assessed using student t-test with significance of P<0.05. According to this study, the results were as follows: 1. IL-8 mRNA was detected in all type of cells studied (PF, GF and PDLF) 2. IL-8 mRNA expression was not increased after stimulating 4 hrs with SP ($10^{-5}M$) and SP ($10^{-8}M$) compared with Mock stimulation in all type of cells studied. 3. IL-8 mRNA expression was not increased after stimulating 8 hrs with SP ($10^{-4}M$) and CGRP ($10^{-6}M$) compared with Mock stimulation in all type or cells studied. 4. TNF-$\alpha$ (2 ng/ml) increased the expression of IL-8 mRNA in all kind of cells studied. 5. The secretion of IL-8 from GF was increased 8 hrs after the stimulation with CGRP ($10^{-6}M$)(p<0.05). 6. The secretion of IL-8 from PDLF was. increased 8 hrs after the stimulation with SP ($10^{-4}M$)(p<0.05). Calcitonin Gene-related Peptide (CGRP) increased Interleukin-8 (IL-8) which plays an important role in chemotaxis of neutrophil in Calcitonin Gene-related Peptide (CGRP) gingival tissue , whereas Substance P increased the secretion of IL-8 from periodontal ligament.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.6
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• pp.323-327
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• 2006

Despite the wealth of data concerning the roles of ${\alpha}-CGRP$ in nociceptive behaviors, ${\alpha}-CGRP-null$ mice showed no obvious phenotypic differences in nociceptive behaviors from wild type. The present studies specifically demonstrate that ${\alpha}-CGRP$ null mice showed no CGRP immunoreactivity from the spinal cord, implying that CGRPs in the mice spinal cord are mainly a-isoforms. However, the nociceptive behaviors of the null mice are not significantly different from the wild type mice in thermal nociceptive behaviors on hotplate, chemical nociception tests to intraplantar capsaicin or formalin injection, and visceral pain behaviors to intraperitoneal acetic acid or magnesium sulfate injections. These data suggest that ${\alpha}-CGRP$ is dispensable for nociceptive behaviors or that compensatory mechanisms may exist to overcome the absence of this peptide.

• Restorative Dentistry and Endodontics
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• v.24 no.1
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• pp.180-186
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• 1999

Eugenol has been reported to reduce odontogenic pain and is known to have a structure similar to capsaicin, a potent stimulant of certain nociceptors. We have hypothesized that the analgesic effect of eugenol may be due, in part, to inhibition of capsaicin-sensitive nociceptors. To test this hypothesis, we evaluate whether eugenol inhibits capsaicin-sensitive release of immunoreactive calcitonin generated peptide(iCGRP) from bovine dental pulp. Freshly extracted bovine incisors were transported to the lab. on ice, Spilitted and pulp tissue was removed. The tissue was chopped into 200${\mu}m$ slices. Dental pulp was superfused(340 ${\mu}l/min$) in vitro with oxygenated Kreb's buffer. Eugenol and vehicle(0.02% 2-hydroxyl-${\beta}$-cyclodextrin) were administered prior to stimulation of pulp with capsaicin and iCGRP was measured by RIA. The results were as follows: 1. Administration of eugenol has no effect on basal release of iCGRP. 2. In the vehicle treated group, capsaicin evoked a 2.5-fold increase over basal iCGRP levels. 3. Administration of eugenol(600 ${\mu}M$) reduced capsaicin evoked release of iCGRP by more than 40%(153.4${\pm}$41.1% vs 258.9${\pm}$21.7%). 4. 2-hydroxylpropyl-${\beta}$-cyclodextrin of less than 0.02% is found to be an effective vehicle to dissolve eugenol without evoking iCGRP release from dental bovine pulp. These data indicate that eugenol inhibits pulpal capsaicin-sensitive fibers and suggest that intracanal medicament of eugenol may relieve pain, in part, by this mechanism.

• BMB Reports
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• v.56 no.4
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• pp.209-215
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• 2023

Maintaining internal homeostasis and regulating innate behaviors are essential for animal survival. In various animal species, a highly conserved neuroendocrine system integrates sensory inputs and regulates physiological responses to environmental and internal changes. Diuretic hormones 44 and 31, which are homologs of mammalian corticotropin-releasing factor (CRF) and calcitonin gene-related peptide (CGRP), respectively, control body fluid secretion in Drosophila. These neuropeptides and their receptors have multiple physiological roles, including the regulation of body-fluid secretion, sleep:wake cycle, internal nutrient-sensing, and CO₂-dependent response. This review discusses the physiological and behavioral roles of DH44 and DH31 signaling pathways, consisting of neuroendocrine cells that secrete DH44 or DH31 peptides and their receptor-expressing organs. Further research is needed to understand the regulatory mechanisms of the behavioral processes mediated by these neuroendocrine systems.

• Anatomy and Cell Biology
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• v.56 no.3
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• pp.304-307
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• 2023

The nervus conarii provides sympathetic nerve innervation to the pineal gland, which is thought to be the primary type of stimulus to this gland. This underreported nerve has been mostly studied in animals. One function of the nervus conarii may be to activate pinealocytes to produce melatonin. Others have also found substance P and calcitonin gene-related peptide from the nervus conarii ending in the pineal gland. The following paper reviews the extant medical literature on the nervus conarii including its anatomy and potential function.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.85-85
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• 1993

뇌동맥계는 일과성 저혈압에 반응하여 혈관확장이 야기되고, 혈압 상승시에는 혈관수축이 일어남으로서 뇌혈류가 일정하게 조절된다. 이러한 자가조절은 뇌손상 등의 병적 상태에서 야기된다. 연구의 목적은 \circled1 Cromakalim, CGRP(calcitonin-gene related peptide), 및 substance P에 의하여 뇌연막동맥의 직경이 어떻게 변동하는가를 관찰하고 \circled2 이들 신경성 peptide의 작용에 대하여 $K^{＋}$ 통로 개방 봉쇄제인 glibenclamide의 전처치 효과를 검색하고 \circled3 Capsaicin 전처치가 뇌혈류 자가조절에 어떻게 영향을 미치는가를 검색하였다. 그 결과는 다음과 같다. 1. 뇌혈류 자가조절은 대퇴동맥을 통한 사혈에 의하여 혈압하강을 일으킬 때 뇌연막 동맥은 이완하였고, reservoir내의 혈액을 체내로 주입함로서 혈압반전을 일으켰을 때는 혈관 수축이 일어났다. 2. 연막동맥은 glibenclamide (1~3$\mu$M)의 관류에 의하여는 영향을 받아니하였다. 3. 혈압변동에 따른 혈관직경의 변화를 회기직선으로 분석하였다. Glibenclamide 1과 3$\mu$M의 전처치 관류에 의하여 혈압하강에 따른 혈관 이완경사도와 혈압반전에 따른 혈관수축 경사도가 대조군에 비하여 현저히 약화되었다. 4. Cromakalim (0.1-30$\mu$M)의 각 농도를 대뇌표면에 관류시 연막동맥의 기초직경은 약물농도에 의존하여 증가되었고, 이는 glibenclamide (1$\mu$M) 전처치 관류에 의하여 억제되었다. 5. CGRP (0.1~100 nM)와 substance P (0.1~10nM)도 용량에 의존하여 혈관이완을 일으켰다. 전자는 glibenclamide (1$\mu$M) 전처치 관류에 의하여 억제되었으나 후자는 영향을 받지 아니하였다. 6. Capsaicin(50 nmol: intracisternally) 주사에 의하여 뇌혈류자가조절의 변동이 초래되었다. 이상의 결과들을 종합하면 CGRP가 혈압변동에 의하여 반사적으로 유리되고, 이는 glibenclamide-sensitive $K^{＋}$ 통로에 작용하는 것으로 시사된다.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.3
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• pp.251-262
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• 1997

Peripheral nerve injury sometimes leads to neuropathic pain and depletion of calcitonin gene related-peptide (CGRP) and substance P (SP) in the spinal cord. However, the pathophysiological mechanisms for depletion of CGRP and SP following the neurorathic injury are still unknown. This study was performed to see whether the distribution of immunoreactivity for CGRP and SP in the superficial dorsal horn and dorsal root ganglia(DRG) was related to the distance between the DRG and injury site. To this aim, we compared two groups of rats; one group was subjected to unilateral inferior and superior caudal trunk transections at the level between the S3 and S4 spinal nerves (S34 group) and the other group at the levels between the S1 and S2, between S2 and S3 and between S3 and S4 spinal nerve (S123 group). The transections in both groups equally eliminated the inputs from the tail to the S1-3 DRG, but the distance from the S1/S2 DRG to the injury site was different between the two groups. Immunostaining with SP and CGRP antibody was done in the S1-S3 spinal cord and DRG of the two groups 1 and 12 weeks after the injury. The results obtained are as follows: 1. The immunoreactivity for CGRP and SP in the ipsilateral superficial dorsal horn and DRG decreased 1 and 12 weeks after neuropathic nerve injury. 2. The immunoreactive area of SP and CGRP in the S1 dorsal horn was smaller in the S123 group than in the S34 group, whereas that in the S3 dorsal horn was not significantly different between the two groups. The number of SP-immunoreactive DRG cells decreased on the neuropathic side as compared to the sham group's in all DRGs of experimental groups except the S1 DRG of the S34 group. These results suggest that the amounts of SP and CGRP in the dorsal horn and DRG following neuropathic injury inversely decrease according to the distance between the DRG and injury site.

• Restorative Dentistry and Endodontics
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• v.24 no.2
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• pp.372-380
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• 1999

The purpose of this study was to investigate the distribution of calcitonin gene-related peptide(CGRP) containing nerve fivers after pulp exposure in rats. The Spague-Dawley rats weighing about 250 - 300g were used. The animals were devided into normal control group and experimental groups. Experimental animals were sacrified on 2, 4, 7, 10 days after pulp exposure. The maxillary teeth and alveolar bone were removed and immersed in the 4% paraformaldehyde plus 0.1M phosphate buffer (pH 7.4). Serial frozen $50{\mu}m$ thick sections were cut with a cryostat. In the immunohistochemical staining procedure, the rabbit CGRP antibody was used as a primary antibody. The sections were incubated for 48 hours at $4^{\circ}C$, and placed into biotinylated anti-rabbit IgG as a secondary antibody and incubated in ABC (avidin-biotin complex), The sections were visualized by 0.05% 3.3 diaminobenzidine tetrahydrochloride. The results of this study were as follows: 1. In control group, CGRP containing nerve fibers ran parallel to the long axis of root and reached the coronal pulp. They were distributed on Raschkow plexus under the odontoblastic layer. 2. In 2 day group after pulp exposure, tissue necrosis and acute inflammation occurred and CGRP containing nerve fibers increased. In 4 day group, the necrotic tissue extended to the pulp and CGRP containing nerve fibers were distributed around the inflammation zone. 3. In 7 day group after pulp exposure, pulp necrosis occurred, and in 10 day group, the abscess under the necrotic pulp extended to the root apex area and CGRP containing nerve fibers were not observed in root canals. 4.The sprouting of CGRP nerve fibers was most remarkable at the pulp chamber under injury in 4 day group, and it was found at inflammation zone under the necrotic tissue in 7 day group and the remaining root pulp tissue in 10 day group. As mentioned above, CGRP nerve fibers had a tendency to increase around the inflammatory zone, especially around the acute inflammation tissue, when compared with control group. It is suggested that CGRP nerve fibers maybe related to the control of inflammatory response of pulp tissue.

• Restorative Dentistry and Endodontics
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• v.24 no.1
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• pp.100-115
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• 1999

The purpose of this study was to investigate the distribution of calcitonin gene-related peptide containing nerve fibers in rat pulp after dentinl injury by means of immunohistochemistry and confocal laser scanning microscope. The Spague-Dawley rats weighing about 250-300gm were used. The animals were devided into normal control and experimental groups. Experimental animals were sacrified 1, 2, 4, 7, 10, 21days after dentinal injury (dentin cutting, and then acid etching with 35% phosphoric acid) on the maxillary molar teeth. The maxillary teeth and alveolar bone were removed and immersed in the 4% paraformaldehyde in 0.1M phosphate buffer (pH 7.4), then were decalcified with 15% formic acid for 10 days. Serial frozen $50{\mu}m$ thick sections were cut on a cryostat. The rabbit CGRP antibody was used as a primary antibody with a dilution of 1:2000 in 0.01M PB. The sections were incubated for 48 hours at $4^{\circ}C$, and placed into biotinylated antirabbit Ig G as a secondary anti body with dilution of 1:200 in 0.01M PB and incubated in ABC(avidin-biotin complex). The peroxidase reaction was visualized by incubating the sections in 0.05% 3,3 diaminobenzidine tetrahydrochloride containing 0.02% $H_2O_2$. For the confocal laser scanning microscopic examination, Primary antibody reaction was same as immunoperoxidase stainning, but fluorescein isothiocyanate(FITC)-conjugate antirabbit IgG as a secondary antibody was used. The confocal laser scanning microscope was used for the examination. A series of images of optical sections was collected with a 20x objective at $3{\mu}m$ intervals throughout the depth of specimen. FITC fluerescence was registrated through a 488nm and 568nm excitation filter, and images were saved on optical disk. The stereoscopic images and three dimentionnal images were reconstructed by computer software, and then were analyzed. The results were as follows : 1. In normal control group, CGRP containing nerve fibers were coursed through the root with very little branching, and then formed a dense network of terminals in coronal pulp. 2. A slight increase in CGRP containing nerve fibers at 1 and 2day postinjury was noted subjacent to the injury site. In the 4day group, there were an extensive increase in the number of reactive fibers, followed by a partial return toward normal levels at 7~10 day postinjury, and return by 21days. 3. The sprouting of the CGRP containing nerve fibers was evident within 2day after dentinal injury, and by 4days there was a maximal increased, but was decreased at 7days and returned to normal 10~21 day postinjury. 4. In confocal laser scanning microscopic exammination, the distinct distribution pattern and sprouting reaction of CGRP containing nerve fibers were observed in stereoscopic images and three dimentional images. These results suggest that CGRP containing nerve fiber can be important role in the response to dental injury and pain regulation.