• Advances in Traditional Medicine
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• v.5 no.3
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• pp.236-239
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• 2005

Effects of Naoxintong (NXT, a formula of Chinese Materia Medica)-containing serum on Nitrogen monoxide (NO) and calcitonin gene related peptide (CGRP) in rat cerebral microvascular endothelial cells (rCMEC) was investigated, rCMEC was injured in vitro by incubating for 4 hours at 100% NO in a hypoxia chamber. The results indicated that NXT could antagonize the reduction of NO and CGRP secreted by rCMEC during hypoxia, the effect of which was dose-dependent. After treated with NXT-containing serum at dosage of 5.0 - 30 and 50 -1.1 g/kg/U respectively, the amount of NO and CGRP secreted by rCMEC were remarkably increased during hypoxia in vitro.

• Journal of the korean academy of Pediatric Dentistry
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• v.35 no.1
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• pp.11-17
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• 2008

The purpose of this study was to investigate early histological changes and calcitonin gene-related peptide (CGRP) expression in the dental pulp of the rat after Er:YAG laser preparation. Occlusal cavities were prepared in the upper first molars using either Er:YAG laser and conventional bur. At 48 hours after cavity preparation, the teeth were processed for hematoxylin-eosin stain and CGRP immunohistochemistry. The results were as follows : 1. The cavity floor by Er:YAG laser preparation was more irregular shape compared with those by bur preparation and there are some cracks in the directions of dentinal tubules. 2. There were more inflammatory cell infiltration and disruption of odontoblast in the dental pulp by Er:YAG laser preparation in comparison with the dental pulp by bur preparation. 3. CGRP expression in the pulp tissue by both Er:YAG laser and bur preparations were increased and higher than in the normal pulp. The expression pattern of CGRP was more strong in the pulp by Er:YAG laser preparation. These results indicate that Er:YAG laser is useful in the operative dentistry such as caries removal and cavity preparation if properly applied.

• Journal of the korean academy of Pediatric Dentistry
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• v.26 no.4
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• pp.688-702
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• 1999

The purpose of this study was to investigate the revascularization and reinnervation of calcitonin gene-related peptide immunoreactive nerves in immediately replanted rat molars. First maxillary right molars in 56 rats(35days old) were extracted and immediately replanted. The rats were killed 1, 2, 3, 7, 14, 28 and 42 days after replantation and revascularization of pulpal blood vessels were examined microangiogram with korean traditional ink and reinnervation of pulpal nerve were examined immunohistochemical method using calcitonin gene-related peptide(CGRP) antiserum. The results were as follows; 1. Revascularization and reinnervation of CGRP immunoreactive nerve fibers were observed mesial side whole pulp tissue of replanted teeth. Revascularization and reinnervation of CGRP immunoreactive fiber were made at 2days after replantation in entire pulp of replanted teeth and the distribution density of blood vessels were gradually increased according time elapsed, but did not achieve the density of control. 2. Postoperative dentin formation in replanted teeth revealed at 1week after replantaton and gradually increased according to time elapsed. 3. Revascularization and Reinnervation of CGRP immunoreactive nerve fibers were established at the same time and it seems to be closed relatationship between revascularization and reinnervation.

• 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.272-278
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• 2002

To investigate the anti-inflammatory and analgesic effects of Herba Chelidoniie, the extracts of Herba Chelidoniie treated in arthritic rat model. Complete Freund,s Adjuvant(CFA) were injected in the subcutaneous tissue of left foot paw of rats to induce arthritis. Herba Chelidonii extracts(HC) was administered immediately into the peritoneal cavity after CFA injection for 12 days. The immunohistochemical stainings for calcitonin gene-related peptide(CGRP) and substance P in the L4, L5 and L6 spinal dorsal horn and ganglia were done, and the paw swelling was measured with a micrometer and the blood leukocytes were counted. The results were as follows : The paw swelling of HC treated group was significantly decreased in 12th day after CFA injection compare to control group. The change of differential leukocytes counts of HC treated group increased the ratio of lymphocytes, and decreased the ratio of neutrophils compare to control group. The extent of CGRP immunoreactive nerve fiber of dorsal horn of HC treated group was weakly stained compare to control group. The number of CGRP immunoreactive neurons of L6 spinal cord of HC treated group was significantly decreased compare to control group. The extent of substance P immunoreactive nerve fiber of dorsal horn of He treated group was weakly stained compare to control group. The number of substance P immunoreactive neurons of L4, L5 and L6 spinal cord of HC treated group was significantly decreased compare to control group. These experimental results suggest that Herba Chelidonii extracts reduce the number of CGRP and substance P immunoreactive neurons and nerve fibers of spinal dorsal horns and ganglia, and decrease paw swelling in arthritic rat model, which may be closely related to analgesic and antiinflammatory effects of Herba Chelidonii.

• The Korean Journal of Pain
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• v.35 no.2
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• pp.173-182
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• 2022

Background: Neurokinin-1 (NK1) and calcitonin gene-related peptide (CGRP) play a vital role in pain pathogenesis, and these proteins' antagonists have attracted attention as promising pharmaceutical candidates. The authors investigated the anti-nociceptive effect of co-administration of the CGRP antagonist and an NK1 antagonist on pain models compared to conventional single regimens. Methods: C57Bl/6J mice underwent sciatic nerve ligation for the neuropathic pain model and were injected with 4% formalin into the hind paw for the inflammatory pain model. Each model was divided into four groups: vehicle, NK1 antagonist, CGRP antagonist, and combination treatment groups. The NK1 antagonist aprepitant (BIBN4096, 1 mg/kg) or the CGRP antagonist olcegepant (MK-0869, 10 mg/kg) was injected intraperitoneally. Mechanical allodynia, thermal hypersensitivity, and anxiety-related behaviors were assessed using the von Frey, hot plate, and elevated plus-maze tests. The flinching and licking responses were also evaluated after formalin injection. Results: Co-administration of aprepitant and olcegepant more significantly alleviated pain behaviors than administration of single agents or vehicle, increasing the mechanical threshold and improving the response latency. Anxiety-related behaviors were also markedly improved after dual treatment compared with either naive mice or the neuropathic pain model in the dual treatment group. Flinching frequency and licking response after formalin injection decreased significantly in the dual treatment group. Isobolographic analysis showed a meaningful additive effect between the two compounds. Conclusions: A combination pharmacological therapy comprised of multiple neuropeptide antagonists could be a more effective therapeutic strategy for alleviating neuropathic or inflammatory pain.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.287-287
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• 1994

In the present study, it was aimed to asses the possibility that calcitonin gene-related peptide (CGRP) released in response to transient hypotension may contribute to the reflex autoregulation of cerebral blood flow as a putative modulator. Changes in pial arterial diameter (mean, 33.0 ${\pm}$ 1.1 $\mu\textrm{m}$) with changes in systemic arterial blood pressure (mean, 101.9 ${\pm}$ 2.7 mmHg) were observed directly through a closed cranial window in anesthetized normotensive rats. Image of the pial vessels was captured with a stereoscope connected to a CCD video camera and the diameter was measured with a microscaler. In the capsaicin-treated rats (one day prior to experiment, 50 nmol capsaicin injected intracisternally), both vasodilater and vasoconstrictor responses evoked by a transient hypotension and the reverse of blood pressure were markedly attenuated or almost abolished. When changes in pial arterial diameter were plotted as a function of changes in blood pressure, the slopes of both regression lines (for vasodilators and vasoconstrictors ) were markedly reduced. Similar reductions were evidenced under treatment wi th the CGRP antibody serum (1:1,000) and following CGRP receptor desensitization. However, the autoregulatory mechanics were neither affected by treatment wi th spantide (1 ${\mu}$M), substance P antagonist, nor by substance P receptor desensitization. Suffusion wi th mock cerebrospinal fluid containing CGRP and cromakalim caused a vasodilatation in a concentration-dependent manner, respectively and their effects were antagonized by glibenclamide. Substance P produced a vasodilatation, which was, however, little affected by glibenclamide. These observations indicate that the CGRP released from the perivascular sensory fibers in response to a hypotension is implicated in the modulation of the autoregulation of cerebral blood flow.

• 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.

• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.573-578
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• 2003

The effects of removing the endothelium on the vasodilatory response to substance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) was examined in the isolated rabbit renal artery. The vasodilator response to substance P ($0.1{\mu}M$) was completely absent in vessels in which the endothelium had previously been removed. There was no significant difference in the vasodilatation produced in response to CGRP ($0.1{\mu}M$), or VIP ($0.1{\mu}M$) in the intact and removed-endothelium rabbit renal artery segments. L-NAME ($100{\mu}M$) significantly reduced the vasodilatory response to substance P ($0.1{\mu}M$). This inhibition was significantly attenuated when L-arginine (10 mM) was also present in the organ bath along with L-NAME ($100{\mu}M$). Indomethacin ($1{\mu}M$) did not significantly affect the vasodilatation produced in response to substance P ($0.1{\mu}M$). The inhibitory effect of L-NAME ($100{\mu}M$) and indomethacin ($1{\mu}M$) on the vasodilatory response to substance P ($0.1{\mu}M$) was not significantly different from that produced by L-NAME ($100{\mu}M$) alone. This study indicates that substance P induced vasodilatation via an endothelium-dependent mechanism in the isolated rabbit renal artery. It also established that CGRP and VIP induced vasodilatation by an endothelium-independent mechanism and substance P-induced vasodilatation is at least partially via NO.

• 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.