• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.153-160
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• 2017

In this study, we aim to determine the in vivo effect of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) on neuropathic pain, using three, principal peripheral neuropathic pain models. Four weeks after hUCB-MSC transplantation, we observed significant antinociceptive effect in hUCB-MSC-transplanted rats compared to that in the vehicle-treated control. Spinal cord cells positive for c-fos, CGRP, p-ERK, p-p 38, MMP-9 and MMP 2 were significantly decreased in only CCI model of hUCB-MSCs-grafted rats, while spinal cord cells positive for CGRP, p-ERK and MMP-2 significantly decreased in SNL model of hUCB-MSCs-grafted rats and spinal cord cells positive for CGRP and MMP-2 significantly decreased in SNI model of hUCB-MSCs-grafted rats, compared to the control 4 weeks or 8weeks after transplantation (p<0.05). However, cells positive for TIMP-2, an endogenous tissue inhibitor of MMP-2, were significantly increased in SNL and SNI models of hUCB-MSCs-grafted rats. Taken together, subcutaneous injection of hUCB-MSCs may have an antinociceptive effect via modulation of pain signaling during pain signal processing within the nervous system, especially for CCI model. Thus, subcutaneous administration of hUCB-MSCs might be beneficial for improving those patients suffering from neuropathic pain by decreasing neuropathic pain activation factors, while increasing neuropathic pain inhibition factor.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.4
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• pp.400-404
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• 2007

The present study was carried out to investigate the antitumor activity of Salvia miltiorrhiza (SM) herbal extract in rat tumor model. We used a new tumor animal model for the invasion and metastasis of cancer using genetically k-ras-induced rat kidney cells (RK3E-ras). We observed tumor as early as 7 days after the injection of RK3E-ras cells in subcutaneous of Sprague-Dawley rats. All of the rats developed tumor mass at the inoculated site. After 7 days, the experimental groups were divided into two: saline control and injected with SM (200 mg/kg) groups. We investigated tumor's weight, size and hepatic metastasis of each group. Injection of SM herbal extract every other day for 14 days significantly inhibited tumor growth. Histologically, the tumors were undifferentiated carcinoma showing multifactorial necrosis and hemorrhage; also, the tumor invaded into hepatoportal region. Treatment with SM herbal extract caused significant inhibition of tumor cell proliferation. Our data showed that SM herbal extract is effective in controlling the tendency of tumor cell proliferation and metastasis by injection of RK3E-ras cells. These findings provided the potential value of SM as a novel antitumor agent candidate.

• Journal of Preventive Medicine and Public Health
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• v.30 no.1 s.56
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• pp.69-76
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• 1997

To exanime in vivo tissue reactions of glass fibers, we injected glass fibers to rats subcutaneously. We made fibers of average dimensions of approximately $2{\mu}m$ in diameter and $60{\mu}m$ in length. After instilation of glass fiber we sacrificed rats sequentially at 1, 3 and 6 months. At 1 month after injection of glass fibers, the exposure area turned to yellow color and formed well-demarcated round mass. The average size of the mass was $1\times0.3cm$. Grossly detectable mass was decreased in size at 6 months compared to 1 or 3 months. Microscopically, strong foreign body reaction to glass fibers, inflammation and fibrosis were observed until 6 months. Foreign body reaction was increased up to 3 months, but it was decreased after 6 months. In scanning electron microscope, there was many bundles of glass fibers around the inflammation area, but the size of glass fibers were gradually reduced from 1 month to 6 months. These results suggest that subcutaneous exposure of glass fiber can provoke strong tissue reaction including foreign body granulomas, inflammation and fibrosis. But glass fiber itself did not produce any neoplastic changes.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.625-637
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• 1997

Calcium ions are implicated in a variety of physiological functions, including enzyme activity, membrane excitability, neurotransmitter release, and synaptic transmission, etc. Calcium antagonists have been known to be effective for the treatment of exertional angina and essential hypertension. Selective and nonselective voltage-dependent calcium channel blockers also have inhibitory action on the acute and tonic pain behaviors resulting from thermal stimulation, subcutaneous formalin injection and nerve injury. This study was undertaken to investigate the effects of iontophoretically applied $Ca^{++}$ and its antagonists on the responses of WDR (wide dynamic range) cells to sensory inputs. The responses of WDR cells to graded electrical stimulation of the afferent nerve and also to thermal stimulation of the receptive field were recorded before and after iontophoretical application of $Ca^{++}$, EGTA, $Mn^{++}$, verapamil, ${\omega}-conotoxin$ GVIA, ${\omega}-conotoxin$ MVIIC and ${\omega}-agatoxin$ IVA. Also studied were the effects of a few calcium antagonists on the C-fiber responses of WDR cells sensitized by subcutaneous injection of mustard oil (10%). Calcium ions and calcium channel antagonists ($Mn^{++}$, verapamil, ${\omega}-conotoxin$ GVIA & ${\omega}-agatoxin$ IVA) current-dependently suppressed the C-fiber responses of WDR cells without any significant effects on the A-fiber responses. But ${\omega}-conotoxin$ MVIIC did not have any inhibitory actions on the responses of WDR cell to A-fiber, C-fiber and thermal stimulation. Iontophoretically applied EGTA augmented the WDR cell responses to C-fiber and thermal stimulations while spinal application of EGTA for about $20{\sim}30\;min$ strongly inhibited the C-fiber responses. The augmenting and the inhibitory actions of EGTA were blocked by calcium ions. The WDR cell responses to thermal stimulation of the receptive field were reduced by iontophoretical application of $Ca^{++}$, verapamil, ${\omega}-agatoxin$ IVA, and ${\omega}-conotoxin$ GVIA but not by ${\omega}-conotoxin$ MVIIC. The responses of WDR cells to C-fiber stimulation were augmented after subcutaneous injection of mustard oil (10%, 0.15 ml) into the receptive field and these sensitized C-fiber responses were strongly suppressed by iontophoretically applied $Ca^{++}$, verapamil, ${\omega}-conotoxin$ GVIA and ${\omega}-agatoxin$ IVA. These experimental findings suggest that in the rat spinal cord, L-, N-, and P-type, but not Q-type, voltage-sensitive calcium channels are implicated in the calcium antagonist-induced inhibition of the normal and the sensitized responses of WDR cells to C-fiber and thermal stimulation, and that the suppressive effect of calcium and augmenting action of EGTA on WDR cell responses are due to changes in excitability of the cell.

• The Korean Journal of Pain
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• v.14 no.1
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• pp.1-6
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• 2001

Background: Subcutaneous injection of 5% formalin into the hind paw of the rat produces a biphasic nociceptive response. The second phase depends on changes in the dorsal horn cell function that occur shortly after an initial C-fiber discharge, spinal sensitization, or windup phenomenon. This study was performed to investigate the role of glutamate during spinal sensitization. Methods: Sprague-Dawley rats weighing 200 to 250 g were used for this study. Under light anesthesia (0.5% isoflurane) the rats were segregated in a specially designed cage and $50{\mu}l$ 0.5% formalin was injected subcutaneously in the foot dorsum of right hindlimb. Forty minutes after the formalin injection, the rat was quickly decapitated and spinal cord was removed. The spinal segments at the level of L3 (largest area) was collected and stored in a deep freezer ($-70^{\circ}C$). The mRNA gene expression of N-methyl-D-aspartate receptor (NMDAR) and the metabotropic glutamate receptor subtype 5 (mGluR5) were determined by the polymerase chain reaction. Results: The number of flinches was $19.8{\pm}2.3/min$. at one minute after formalin injection and decreased to zero after then. The second peak appeared at 35 and 40 minutes after formalin injection. The values were $17.8{\pm}2.2$ and $17.2{\pm}3.0/min$. The mRNA gene expressions of NMDAR and mGluR5 were increased by $459.0{\pm}46.8%$ (P < 0.01) and $111.1{\pm}4.8%$ (P > 0.05) respectively at 40 minutes after formalin injection. The increased rate of NMDAR was significantly higher than that of mGluR5 (P < 0.01). Conclusions: From these results it suggested that NMDAR partly contributed to the mechanism of central sensitization after the formalin test but mGluR5 did not.

• Korean Journal of Veterinary Research
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• v.40 no.4
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• pp.677-681
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• 2000

Since the role of female sexual hormones on pancreatic exocrine secretion was not fully understood, this study was investigated to clarify the difference of spontaneous pancreatic exocrine responses during the estrous cycle and the roles of ovarian hormones on pancreatic exocrine secretion in the anesthetized female rats. Pancreatic juice was collected from the sequential 15-min samples, and then fluid and protein secretion were measured from the collected samples. The stages of estrous cycle were defined by staining the vaginal smear. The spontaneous pancreatic fluid and protein secretion were significantly increased during the diestrus stage compare to the corresponding value during the estrus stage. In the ovariectomized rat, spontaneous pancreatic exocrine secretion was significantly decreased compare to the value of female rat during the diestrus stage and was restored by subcutaneous injection of progesterone (50 mg/kg). This results suggest that the spontaneous pancreatic exocrine secretion of female rat is fluctuated according to the estrous cycle and progesterone released from ovary could stimulate the spontaneous pancreatic exocrine secretion of female rat.

• Advances in Traditional Medicine
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• v.7 no.5
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• pp.501-508
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• 2008

Anti-nociceptive and anti-inflammatory effects of Clematidis Radix (CR)-distillates were investigated in three different pain animal models. Highly purified distillate of CR was injected to Zusanli (ST36) acupoint, called CR herb-acupuncture in the Korean traditional medicine. In tail flick latency test, the CR herb-acupuncture treatment did not show a significant effect of relieving acute phasic pain. To investigate the anti-inflammatory effect of CR herb-acupuncture, inflammatory pain was induced by subcutaneous injection of formalin to the plantar tissue or intra-articular injection of carrageenan to the tibio-tarsal joint in the rats. And the medicinal effect of CR herb-acupuncture was evaluated by analyzing pain behavior such as licking or biting behavior, or by measuring weight distribution ratio between two foot and ankle circumference. In the rat formalin test, the analgesic effect of CR herb-acupuncture was more pronounced in the late phase (for 20 min after the early phase) than in the early phase (for the first 10 min post formalin injection). It also significantly alleviated the carrageenan-induced monoarthritis, in terms of weight distribution ratio and ankle edema. These results revealed that CR herb-acupuncture was effective to treat the inflammatory pain and could be used as an analgesic treatment with an antiinflammatory effect.

• Journal of Acupuncture Research
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• v.20 no.4
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• pp.24-41
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• 2003

Objective: Dopamine activity in thenucleus accumbens is an important neuropharmacological component of morphine reinforcement. In this nucleus a shell and core have been distinguished on the basis of anatomical and neurochemical criteria. Although acupuncture has been standard intervention in many detoxication programs worldwide, the central mechanism by which morphine acts to reinforce behavior remain elusive. The present in vivo microdialysis study was conducted, in freely moving rats, to detect the effects of acupuncture on extracellular dopamine release in the nucleus accumbens. Methods: Male Sprague-Dawley rats received acupuncture for 1 min after injection of morphine hydrochloride (5mg/kg, s.c.). The employed acupuncture needle points corresponded to bilateral Neiguan(PC6) on the pericardium channel, which has been used to treat mental and psychosomatic disorders. Extracellular dopamine and its metabolites were measured every 20 mins for 3 hrs following the subcutaneous morphine injection. Results: Results showed that acupuncture at PC6 significantly attenuated increases in dopamine levels induced by a single acute morphine injection in the nucleus accumbens shell and core, respectively. Conclusions: These results provided strong evidence for acupuncture-mediated reduction in morphine-induced dopamine release in the rat nucleus accumbens.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.117-123
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• 2002

To investigate the antiinflammatory and analgesic effects of Sophorae radix extracts administered to the arthritic rat model, immunohistochemical stains for CGRP in the L4, L5 and L6 spinal cord and ganglia were done, and paw swelling thickness were measured. Complete Freund,s Adjuvant(CFA) were injected to subcutaneous tissue of left foot paw of rats to induce arthritis. Sophorae radix extracts was administered immediately after CFA injection for 10 days. The spinal cord and ganglia were frozen sectioned(30㎛). These sections were stained by CGRP immunohistochemical staining method, and observed with light microscope. The results were as follows : 1. The change of paw swelling thickness of experimental group decreased from 4 day to 10day after CFA injection compared to control group. 2. The change of differential leukocytes counts of experimental group increased the ratio of lymphocytes. and decreased the ratio of neutrophils compared to control group. 3. The change of CGRP immunoreactive nerve fiber of dorsal horn of experimental group was dense stained compared to control group. 4. The number of CGRP immunoreactive neurons of L4 and L5 spinal cord of experimental group was less than in those control group. These results suggested that Sophorae radix extracts reduces the number of CGRP immunoreactive neurons and nerve fibers of spinal cord and ganglia, and decrease paw swelling thickness in arthritic rat model, which may be closely related to analgesic and antiinflammatory effects of Sophorae radix.

• Archives of Plastic Surgery
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• v.36 no.3
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• pp.269-276
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• 2009

Purpose: Local skin necrosis after extravasation of adriamycin, a widely used chemotherapeutic agent, is a common problem in cancer patients. The extravasation of chemotherapeutic agents yields severe inflammatory responses, crust formation, skin necrosis, and ulceration. Even though several treatment options have been proposed for extravasation injury, there is still controversy regarding the management of such lesions. Thus the aim of this study was to compare the efficacy of saline injection(Group 1), hydrocortisone injection(Group 2), propranolol injection(Group 3) and early surgical excision as a treatment(Group 4) in a rat extravasation model. Methods: The authors planned forty mature male Sprague - Dawley rats were divided into 4 groups and each group contained 10 rats. Administration of adriamycin($1.0mg/m{\ell}$) $1.5m{\ell}$ by subcutaneous injection on the dorsal side of the rats was followed by protocol. The treatment options were applied 2 hours after adriamycin injection. At the end of the 5th days, the presence and size of ulcers at the injection site were measured. 3 weeks after injection, a histopathologic examination was performed for each treatment and control group. T - tests were used to analyze the differences between the measurements. Results: Propranolol significantly improved tissue recovery compared with control group and other groups. These data suggest that there is little role for saline and hydrocortisone in the treatment of adriamycin extravasation injury. Conclusion: In this study, we compared some treatment methods in adriamycin extravasation model. The findings support the propranolol injection may prevent extravasation injury. However this study was performed in the laboratory using rats, and the results could be different in clinical application. Thus, more needs further investigations and clinical application.