• The Korean Journal of Physiology and Pharmacology
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• 제10권1호
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• pp.45-50
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• 2006

Melittin-induced pain model has been known to be very useful for the study of pain mechanism. Melittin-induced nociceptive responses are reported to be modulated by the changes in the activity of excitatory amino acid receptor, calcium channel, spinal serotonin receptor and extracellular signaling-regulated kinase. The present study was undertaken to investigate the role of cyclooxygenase (COX) in the melittin-induced nociception. Changes in mechanical threshold, flinchings and paw thickness were measured before and after intraplantar injection of melittin in the rat hind paw. Also studied were the effects of intraperitonealy administered diclofenac (25 mg & 50 mg/kg), piroxicam (10 mg & 20 mg/kg) and meloxicam (10 mg & 20 mg/kg) on the melittin-induced nociceptions. Intraplantar injection of melittin caused marked reduction of mechanical threshold that was dose-dependently attenuated by non-selective COX inhibitor (diclofenac) and selective COX-1 inhibitor (piroxicam), but not by COX-2 inhibitor (meloxicam). Melittin-induced flinchings were strongly suppressed by non-selective COX and COX-1 inhibitor, but not by COX-2 inhibitor. None of the COX inhibitors had inhibitory effects on melittin-induced increase of paw thickness (edema). These experimental findings suggest that COX-1 plays an important role in the melittin-induced nociceptive responses.

• Fisheries and Aquatic Sciences
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• 제5권1호
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• pp.28-31
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• 2002

Effects of cimetidine, a cytochrome P450 inhibitor, on the benzo[a]pyrene (BaP)-mediated cytochrome P450 induction and lipid peroxidation of liver in olive flounder, Paralichthys olivaceus, were investigated. Fish were fed either a cimetidine-supplemented diet or a cimetidine-free control diet once daily to satiation for 3 days. After 6 hrs of last feeding, the fish received intraperitoneal (i.p.) injection of BaP (20 mg/kg of body weight) dissolved in sterile corn oil $(100 \mu L)$ or received only a corn oil i.p. injection. At 1, 2, 3, and 7 days after the injection, hepatic cytochrome P450 and thiobarbituric acid reactive substances (TBARS), an indicator of lipid peroxidation, were analyzed. BaP injection resulted in an increase of hepatic cytochrome P450, and the fish fed the cimetidine-supplemented diet before injection of BaP showed delayed increase of hepatic cytochrome P450 compared to the fish fed a cimetidine-free diet and BaP injected. Injection of BaP clearly induced hepatic lipid peroxidation, and consistently higher TBAR values were shown in the fish fed a cimetidine­supplemented diet before injection of BaP than the fish injected with BaP alone.

• Clinical and Experimental Reproductive Medicine
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• 제20권1호
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• pp.19-29
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• 1993

Plasminogen activator (PA)-plasmin system in follicular fluid is involved in the process leading to follicular rupture at ovulation. It is well known that PA is closely associated with cellular differentiation and tissue remodeling on evidences from the study of normal and malignant tissues. This study was designed to ascertain a potential role of PA in the ovarian folliculogenesis. Immature Sprague-Dawley rats were injected with pregnant mare serum gonadotropin, followed by injection of serine protease inhibitor (SPI; mixture of 1 mol/L benzamidine and 1 mol/L amino-caproic acid) into the unilateral ovarian bursa. In the control study, mechanical effect of bursal injection and contralateral ovarian effect SPI were ruled out. Total antral follicular areas relative to total ovarian cross-sectional areas was siginificantly lower in SPI-injected ovary than in saline-injected ovary. SPI injection decreased the relative antral follicular area by 33 % respectively. Electron microscopic finding of granulosa cell in the atretic follicle showed the presence of pyknotic nucleus, blurring of neucleolemma, degeneration of mitochondria and dilation of endoplasmic reticulum. After induction of ovulation with hCG, the number of oocytes released was significantly decreased in SPI-injected oviduct than in saline-injected oviduct. From above results, author discussed that PA may play a role not only in ovulation but also in some processes of folliculogenesis.

• The Korean Journal of Pain
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• 제19권2호
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• pp.142-145
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• 2006

Background: Nitric oxide (NO) is involved in the transmission and modulation of nociceptive information at the peripheral, spinal cord and supraspinal levels. We conducted this experiment to assess the antinociceptive effects of a nonselective nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on the modulation of pain in rats subjected to the formalin test. Methods: Formalin 5% was injected in the right hind paw after intraperitoneal (IP) injection of various doses of L-NAME (0.5 mg/kg, 1.5 mg/kg with and without L-arginine 100 mg/kg, 5.0 mg/kg). The number of flinches was measured. Results: Formalin injected into the rat hind paw induced a biphasic nociceptive behavior. IP injected L-NAME diminished the nociceptive behaviors in a dose-dependent manner during phases 1 and 2. The concomitant injection of L-arginine reversed the antinocipetive effect of L-NAME. Conclusions: The data demonstrates that a nonselective NOS inhibitor, L-NAME, possesses antinociceptive properties in rats subjected to the formalin test, and the antinociceptive effect of L-NAME is reversed by the concomitant administration of L-arginine.

• 대한후두음성언어의학회지
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• 제28권1호
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• pp.32-37
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• 2017

Background and Objectives : This study evaluated the efficacy of combination therapy of proton pump inhibitor (PPI) and steroid inhaler (SI), with or without botulinum toxin injection (BTX) for contact granuloma. Subjects and Methods : Fourteen contact granuloma patients were enrolled in this study. Combination therapy of PPI and SI were used for the first line treatment. When combination therapy was not effective, BTX was performed as the second method. Treatment results were recorded as responsible or non-responsible. Farwell grade, size, history of voice abuse, gender, and reflux finding score (RFS) were compared between responsible group and non-responsible group. Results : Initial response rate was 28.6% after treatment of PPI and SI. BTX was performed on three un-responsible patients. After BTX injection, three patients had complete remission of granuloma. Final response rate was 50.0%. Un-responsible group had significantly higher RFS than responsible group. Conclusion : The efficacy of PPI and SI was limited for contact granuloma in this study. Botulium toxin injection was recommended in early phase when PPI and SI did not effective for contact granuloma. Prospective studies evaluating the effects of PPI and SI are warranted.

• International Journal of Oral Biology
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• 제41권3호
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• pp.125-131
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• 2016

The aim of the present study was to develop an animal model for evaluation of temporomandibular (TMJ) nociception under TMJ inflammation. We also investigated the participation of $IL-1{\beta}$ in inflammation-induced TMJ nociception. Experiments were carried out using male Sprague-Dawley rats. Intra-articular injection of 3% formalin was administered to evaluate hyperalgesia 3 days after CFA injection. Intra-articular injection of 3% formalin did not produce nociceptive behavior in normal rats. Although intra-articular injection of 3 doses of CFA produced TMJ inflammation, only 1:3 diluted CFA produced hyperalgesia when formalin was injected intra-articularly 3 days after CFA injection. Co-administration of IL-1 receptor inhibitor with formalin into the TMJ cavity 3 days after CFA injection was performed. Co-administration of IL-1 receptor inhibitor significantly inhibited formalin-induced hyperalgesia in rats with CFA-induced TMJ inflammation. These results suggested that intra-articular injection of formalin produced hyperalgesia under chronic TMJ inflammation. Moreover, $IL-1{\beta}$ plays an important role in TMJ hyperalgesia under chronic inflammation and blockade of $IL-1{\beta}$ is a potential therapeutic target for inflammatory TMJ pain.

• The Korean Journal of Pain
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• 제24권4호
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• pp.179-184
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• 2011

Background: The analgesic mechanisms of cyclooxygenase (COX)-2 inhibitors have been explained mainly on the basis of the inhibition of prostaglandin biosynthesis. However, several lines of evidence suggest that their analgesic effects are mediated through serotonergic or adrenergic transmissions. We investigated the roles of these neurotransmitters in the antinociception of a selective COX-2 inhibitor at the spinal level. Methods: DUP-697, a selective COX-2 inhibitor, was delivered through an intrathecal catheter to male Sprague-Dawley rats to examine its effect on the flinching responses evoked by formalin injection into the hindpaw. Subsequently, the effects of intrathecal pretreatment with dihydroergocristine, prazosin, and yohimbine, which are serotonergic, ${\alpha}1$ adrenergic and ${\alpha}2$ adrenergic receptor antagonists, respectively, on the analgesia induced by DUP-697 were assessed. Results: Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2. But, intrathecal dihydroergocristine, prazosin, and yohimbine had little effect on the antinociception of intrathecal DUP-697 during both phases of the formalin test. Conclusions: Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. Either the serotonergic or adrenergic transmissions might not be involved in the analgesic activity of COX-2 inhibitors at the spinal level.

• The Korean Journal of Physiology and Pharmacology
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• 제5권2호
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• pp.133-138
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• 2001

In the present study, we investigated the effect of pretreatment of p-chlorophenylalanine (PCPA), inhibitor of serotonin synthesis, on lipopolysaccharide (LPS)-induced anorexia in rats. First of all, effects of PCPA injection on food intake and body weight in rats were investigated. During 4 days of PCPA injection (300 mg/kg BW once a day), food intake was decreased by 33% and daily gain in body weight was inhibited compared with controls. Twenty-four hours after last PCPA injection, food intake and gain in body weight returned toward almost normal. Pair-feeding to PCPA (PCPAP) injection revealed that body weight of rats in PCPA group was not different from rats in PCPAP groups. To quantify the effects of LPS on food intake and body weight, we administered varying doses $(10,\;100,\;500\;{\mu}g/kg\;BW)$ of LPS to rats. LPS induced a reduction of food intake and weight loss in a dose dependent manner compared with controls. To evaluate the effects of PCPA pretreatment on LPS injection, rats were treated with PCPA for 4 days (300 mg/kg BW once a day), which was followed by LPS injection for 2 days $(500\;{\mu}g/kg\;BW\;once\;a\;day)$ (PCPA+LPS group), while rats in LPS group had injections with normal saline instead of PCPA for 4 days, which was followed by LPS administration. Rats in control group received 0.9% NaCl for 6 days. LPS decreased food intake by 80% and inhibited gain in body weight, while PCPA pretreated rats showed normalized food intake and gain in weight during the days of LPS injections compared with controls. In conclusion, pretreatment of PCPA prevented LPS-induced anorexia.

• Journal of Ginseng Research
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• 제24권4호
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• pp.168-175
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• 2000

Xenopus oocytes를 이용하여 인삼의 유효 성분으로 알려진 Ginseng total saponin(GTS)의 신호 전달 기작을 two electrode voltage clamp 방법을 이용하여 연구하였다. GTS는 세포 바깥에 처리했을 때 -2OmV보다 더 positive한 voltage에서 커다란 outward current를 유도하였다. 그러나, 세포 안쪽에 GTS를 injection할 경우 아무런 효과가 없는 것으로 나타났다. GTS처리에 의한 outward current유발 효과는 GTS 투여 용량에 의존적인 것으로 나타났다(EC$_{50}$ : 4.4 $\mu\textrm{g}$/ml). GTS의 작용은 $Ca^{2+}$-activated Cl- channel blocker인 niflumic acid에 의하여 차단되었다. 칼슘 chelator인 BAPIA와 IP$_3$ 수용체 길항제인 heparin을 세포내 injection에 의하여 차단되었다. 또한 active phospholipase C inhibitor(PLC)인U-73122를 세포 바깥에 전처리할 경우에도 GTS의 작용이 부분적으로 억제되는 것으로 나타났다. 백일해 독소를 전처리할 경우GTS의 작용은 억제되지 않은 것으로 나타났으나, GTP analog인 GTP${\gamma}$S를 세포내 injection할 경우 GTS의 작용은 억제되는 것으로 나타났다. 이러한 연구 결과는 GTS가 oocytes세포막 성분과 상호 작용에 의하여 $Ca^{2+}$-activated Cl- channel이 열리도록 하고, 이 과정에 PLC활성 및 백일해 독소에 민감하지 않은 G단백질활성 및 IP3에 민감한 세포내 $Ca^{2+}$-activated로부터 칼슘 방출을 유도하는 것으로 나타났다났다

• International Journal of Oral Biology
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• 제42권1호
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• pp.1-8
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• 2017

In the present study, we investigated the role of peripheral ionotropic receptors in artemin-induced thermal hyperalgesia in the orofacial area. Male Sprague-Dawley rats weighting 230 to 280 g were used in the study. Under anesthesia, a polyethylene tube was implanted in the subcutaneous area of the vibrissa pad, which enabled drug-injection. After subcutaneous injection of artemin, changes in air-puff thresholds and head withdrawal latency time were evaluated. Subcutaneous injection of artemin (0.5 or $1{\mu}g$) produced significant thermal hyperalgesia in a dose-dependent manner. However, subcutaneous injection of artemin showed no effect on air-puff thresholds. IRTX ($4{\mu}g$), a TRPV1 receptor antagonist, D-AP5 (40 or $80{\mu}g$), an NMDA receptor antagonist, or NBQX (20 or $40{\mu}g$), an AMPA receptor antagonist, was injected subcutaneously 10 min prior to the artemin injection. Pretreatment with IRTX and D-AP5 significantly inhibited the artemin-induced thermal hyperalgesia. In contrast, pretreatment with both doses of NBQX showed no effect on artemin-induced thermal hyperalgesia. Moreover, pretreatment with H-89, a PKA inhibitor, and chelerythrine, a PKC inhibitor, decreased the artemin-induced thermal hyperalgesia. These results suggested that artemin-induced thermal hyperalgesia is mediated by the sensitized peripheral TRPV1 and NMDA receptor via activation of protein kinases.