• Natural Product Sciences
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• v.20 no.4
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• pp.285-289
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• 2014

Pyrrosia lingua has been widely used as a traditional medicine for the treatment of lots of diseases including pain management. However pharmacological and phytochemical studies on its anti-nociceptive properties are extremely limited. In this work, we investigated the effects of methanol extract of Pyrrosia lingua (MPL, 250 and 500 mg/kg) on the both of central and peripheral nociceptive pain. The results from tail-immersion test and hotplate test revealed that MPL has potent anti-nociceptive effects on thermal nociception. In addition, MPL efficiently reduced the acetic acid-induced chemical nociception compared to indomethacin. We also carried out formalin test and MPL reduced formalin-induced pain response on both phases, suggesting MPL has antinociceptive activities on the central and peripheral pain. In combination test using naloxone, anti-nocicpetive activity of MPL was reduced, indicating that MPL acts as a partial opioid receptor agonist. These results suggest that MPL may be possibly used as a valuable natural product-derived painkiller.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.365-371
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• 2006

Bee Venom aqua-acupuncture (BVA) simultaneously exerts pharmacological effects of biologically active compounds, existed in the whole bee venom, and medicinal effect of the stimulation of acupuncture points. BVA has been considered as a promising therapeutic method for treating various chronic diseases, mainly accompanying severe pain and inflammation. As a painless injection device, jet injectors have been commercially marketed for various clinical applications including insulin injection and vaccination. Among them, a pressure-driven jet injector system could be used for intradermal delivery of a variety of drugs. The aim of this study was to investigate the analgesic effects of the BVA using a needle-free injector (Biojector $2000^{\circledR}$, Bioject Inc., OR, USA), compared to the conventional BV aqua-acupuncture using a typical syringe. Adult Sprague-Dawley rats were injected with bee venom $(0.08mg/kg,\;50{\mu}l)$ using Biojector $2000^{\circledR}$ (BVA-B) or a syringe (BVA-5) into the Zusanli (ST36) acupoint, 30 minutes before plantar injection of 2% formalin. It was found that BVA-B-, or BVA-5-treated rats, compared to controls, exhibited significantly less licking behavior during the late phase in the rat formalin test, when compared to controls. During early phase, however, those effects were not significant but substantial. The analgesic effect of BVA-B was also compatible with that of the conventional BVA-5. In the immunohistochemical studies, BVA-B significantly suppressed the expression of formalin-evoked c-fos, a biomarker of neuronal activity, in the lumbar dorsal horn of the spinal cord. These results indicated that BVA-B waseffective in the modulation of pain in the rat formalin test, compared to BVA-5. Taken together, the needle-free jet injector system could be substituted for the conventional aqua- acupuncture with the advantage of little pain.

• Journal of Acupuncture Research
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• v.36 no.3
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• pp.147-153
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• 2019

Background: The aim of this study was to investigate the safety and analgesic effects of Datura Flos pharmacopuncture (DFP). Methods: The analgesic effects of DFP were assessed using mechanical (hot plate), chemical (formalin test), and thermal (von Frey filament test) pain tests. Forty male Sprague Dawley rats were assigned randomly into DFP (75 mg/kg, 150 mg/kg), lidocaine 0.5%, or normal saline group for treatment on Kl3. Gross pathology, histopathology, biochemistry and hematology were performed. Results: In the hot plate test, DFP at a high dose (HDDFP; 150 mg/kg) produced a significant analgesic effect, at 10 and 20-minutes post injection (p < 0.01). Low dose DFP (LDDFP; 75 mg/kg) also showed an analgesic effect at 10 minutes post injection (p < 0.01). In the formalin test, HDDFP produced an analgesic effect, for 0-10 and 10-20 minutes (p < 0.01) post treatment, whereas LDDFP showed analgesic effects between 10-20 minutes (p < 0.05). In the von Frey filament test, DF-H produced an analgesic effect, 10 (p < 0.01) and 20 minutes post treatment (p < 0.05). LDDFP showed analgesic effect at 10 minutes (p < 0.05). In the acupuncture response test, HDDFP produced an analgesic effect at 10 minutes post treatment (p < 0.05). DF-H did not cause any anatomical changes to the liver or kidney and there were no abnormalities in biochemistry or hematology. Conclusion: DF-H was not toxic and provided short term analgesia, suggesting it may be useful in the management of pain.

• The Korean Journal of Pain
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• v.18 no.2
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• pp.113-117
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• 2005

Background: Serotonin 3 receptor is involved in the modulation of nociceptive transmission in the spinal cord. The serotonin 3 receptor antagonist has been used for the management of opioid-induced nausea and vomiting. The aim of this study was to examine whether the analgesic effect of morphine is antagonized by serotonin 3 receptor antagonists at the spinal level. Methods: Rats were implanted with lumbar intrathecal catheters. For nociception, a formalin solution (5%, $50{\mu}l$) was injected into the hind paw of male Sprague-Dawley rats. To determine whether the effect of intrathecal morphine was mediated via serotonin 3 receptors, serotonin 3 receptor antagonists were intrathecally administered 10 min prior to the morphine delivery. Following the formalin injection, formalin-induced nociceptive behavior (flinching response) was observed for 60 min. Results: Intrathecal morphine produced a dose-dependent suppression of the flinches in both phases during the formalin test. The analgesic action of morphine was not reversed by serotonin 3 receptor antagonists (LY-278,584, ondansetron), which had little per se effect on the formalin-induced nociception. Conclusions: Spinal serotonin 3 receptors may not be involved in the analgesia of morphine on a nociceptive state evoked by a formalin stimulus.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.4
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• pp.381-388
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• 2020

The quality control of pathological specimens is important for accurate molecular pathology testing. This study evaluated that specimen factors affecting the DNA quality during tissue processing and sample types for BRAF, EGFR, and KRAS mutations tests. One thousand seven hundred and seventy-two molecular pathology tests were investigated for the factors influencing the DNA quality, such as sample type, formalin fixation time, and reexamination status. Cytology samples stored in a saline solution had better DNA quality than commercial cytology preservation. Tissue samples fixed in formalin within 24 hours had better DNA quality than the samples fixed over 24 hours. Between the types of samples, fresh tissue samples and tissue samples with a high tumor cell density had relatively better DNA quality than the formalin-fixed paraffin-embedded (FFPE) tissues and cytology specimens. Of real-time PCR, the non-PNA Ct value increased proportionally with samples held for longer than 24 hours in formalin, and that the formalin-fixed time affects the sample DNA quality. In conclusion, the appropriate tumor cellularity and 10% neutral formalin fixation time are the most important factors for maintaining the DNA quality. These factors should be managed properly for an accurate pathological molecular test to ensure optimal DNA quality.

• Journal of fish pathology
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• v.35 no.1
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• pp.113-120
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• 2022

Scuticociliatosis caused by Miamiensis avidus is a very important parasitic disease in olive flounder farming industry. The aim of this study was to determine effect of combined treatment with blue LED (light-emitting diode) illumination and formalin on olive flounder (Paralichthys olivaceus) infected with M. avidus. Different intensity of 405 nm LED (20, 40, and 60 μmol·m^-2·s^-1) was illuminated on 2.2×10⁴ cells/well of M. avidus in a 24 well microplate for 24 h. Also, 2.4×10⁴ cells/well of M. avidus were exposed to varying combinations of 60 μmol·m^-2·s^-1 of 405 nm LED and serial 10-fold dilutions of formalin (from 10 to 100 ppm) for 15, 30, 45, and 60 min. Surviving M. avidus were counted using a hemocytometer. For in vivo test, flounder acclimatized at 11-12 practical salinity unit (psu) were challenged with 2×10⁶ cells/ml of M. avidus by immersion method for 1 h. Then, fish were moved and divided into four groups; "F" group, treated with formalin at 50 ppm; "L" group, treated with 60 μmol·m^-2·s^-1 of 405 nm LED; "C" group, treated with combination of the two methods; and the control group. After treatment for 30 min, fish were transferred to new tanks (salinity = 11-12 psu) and observed for 3 weeks. As a result, illumination of 405 nm LED at 60 μmol·m^-2·s^-1 killed 100% of M. avidus after 12 h, while 67% and 90% of the scuticociliate died at 20 and 40 μmol·m^-2·s^-1, respectively, after 24 h exposure. One hundred percent of M. avidus was killed at 90, 80, 80 and 70 ppm after exposure to formalin for 15, 30, 45 and 60 min, respectively. However, combined method (e.g., 60 μmol·m^-2·s^-1 of 405 nm-LED plus 50 ppm formalin) killed the parasite within 30 min. From in vivo test, similarly, survival rates of fish challenged with M. avidus were 100%, 43%, 29% and 0% in the C, F, L, and control groups, respectively. Results obtained in this study demonstrates that the combined treatment method has clear synergistic effect on scuticociliatosis in fish.

• Journal of Acupuncture Research
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• v.33 no.3
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• pp.17-28
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• 2016

Objectives : This study was designed to investigate the analgesic effects of Taxus cuspidata pharmacopuncture(TCP) at KI03 on formalin-induced pain in rats and to evaluate the efficiency of different extraction methods of Taxus cuspidata(TC). Methods : 30 rats were divided into 5 groups, each consisting of 6 rats. Each of the groups was treated two times. The first treatment for its right KI03 was as follows: rats were treated with normal saline(NOR), normal saline(CON), hot-water extraction of TC(W), ethanol extraction of TC(E), and ultrasonification extraction of TC(U). The second treatment was given 35 mins after the first one. Rats in NOR were treated with normal saline at their hind-paw. All groups, except NOR, were treated with formalin(5 %, $40{\mu}{\ell}$) at their hind-paw. To evaluate pain behavior, Ultrasonic vocalization(USV) was examined to be around 18~30 kHz. After analysis of USV, blood samples were taken from the rats for analysis of Substance P, aspartate aminotransferase(AST) and alanine aminotransferase(ALT). Results : In the experimental groups, USV was significantly decreased compared with CON and similar to that of NOR in the early phase. But there were no significant differences among the three extraction methods of TC. In addition, Substance P of W was significantly decreased. AST and ALT activation showed no significant differences among the 5 groups. Conclusion : These results show that regardless of extraction methods of TC, TCP at KI03 has analgesic effects in the early phase on formalin-induced pain in rats. In particular, hot-water extraction of TC significantly reduces Substance P activation.

• The Korean Journal of Pain
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• v.20 no.1
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• pp.21-25
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• 2007

Background: Intrathecal sildenafil has produced antinociception by increasing the cGMP through inhibition of phosphodiesterase 5. Spinal opioid receptor has been reported to be involved in the modulation of nociceptive transmission. The aim of this study was to examine the role of opioid receptor in the effect of sildenafil on the nociception evoked by formalin injection. Methods: Rats were implanted with lumbar intrathecal catheters. Formalin testing was used as a nociceptive model. Formalin-induced nociceptive behavior (flinching response) was observed. To clarify the role of the opioid receptor for the analgesic action of sildenafil, naloxone was administered intrathecally 10 min before sildenafil delivery, and formalin was then injected 10 min later. Results: Intrathecal sildenafil produced dose-dependent suppression of flinches in both phases during the formalin test. Intrathecal naloxone reversed the analgesic effect of sildenafil in both phases. Conclusions: Sildenafil is active against the nociceptive state that's evoked by a formalin stimulus, and the opioid receptor is involved in the analgesic action of sildenafil at thespinal level.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.121-127
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• 2014

Acupuncture is the process of stimulating skin regions called meridians or acupoints and has been used to treat pain-related symptoms. However, the pain-relieving effects of acupuncture may be different depending on acupoints. In the present study, the effects of acupuncture on behavioral responses and c-Fos expression were evaluated using a formalin test in male Sprague-Dawley rats in order to clarify the analgesic effects of three different acupoints. Each rat received manual acupuncture at the ST36 (Zusanli), SP9 (Yinlingquan) or BL60 (Kunlun) acupoint before formalin injection. Flinching and licking behaviors were counted by two blinded investigators. Fos-like immunoreactivity was examined by immunohistochemistry in the rat spinal cord. Manual acupuncture treatment at BL60 acupoint showed significant inhibition in flinching behavior but not in licking. Manual acupuncture at ST36 or SP9 tended to inhibit flinching and licking behaviors but the effects were not statistically significant. The acupuncture at ST36, SP9, or BL60 reduced c-Fos expression as compared with the control group. These results suggest that acupuncture especially at the BL60 acupoint is more effective in relieving inflammatory pain than other acupoints.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.289-294
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• 2013

Lipocalin-2 (LCN2) is an acute-phase protein induced by injury, infection, or other inflammatory stimuli. LCN2 binds small hydrophobic ligands and interacts with cell surface receptor to regulate diverse cellular processes. The role of LCN2 as a chemokine inducer in the central nervous system (CNS) has been previously reported. Based on the previous participation of LCN2 in neuroinflammation, we investigated the role of LCN2 in formalin-induced nociception and pathological pain. Formalin-induced nociceptive behaviors (licking/biting) and spinal microglial activation were significantly reduced in the second or late phase of the formalin test in Lcn2 knockout mice. Likewise, antibody-mediated neutralization of spinal LCN2 attenuated the mechanical hypersensitivity induced by peripheral nerve injury in mice. Taken together, our results suggest that LCN2 can be therapeutically targeted, presumably for both prevention and reversal of acute inflammatory pain as well as pathological pain.