• 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.

• Journal of Acupuncture Research
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• v.33 no.1
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• pp.37-46
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• 2016

Objectives : The objective of this study is to evaluate the analgesic effects of Drosera rotundifolia L. pharmacopuncture on formalin-induced pain in Sprague-Dawley(SD) rats. Methods : In this experiment there were four groups, each with six SD rats. In the normal group (NOR), normal saline $40{\mu}L$ was injected at right KI3, and normal saline $40{\mu}L$ was injected at right hindpaw 35 minutes later. In the control group (CON), normal saline $40{\mu}L$ was injected at right KI3, and formalin 5 % $40{\mu}L$ was injected at right hindpaw 35 minutes later. In the Drosera rotundifolia L. pharmacopuncture 3 % group (DP3), Drosera rotundifolia L. pharmacopuncture 3 % $40{\mu}L$ was injected at right KI3, and formalin 5 % $40{\mu}L$ was injected at right hindpaw 35 minutes later. In the Drosera rotundifolia L. pharmacopuncture 5 % group (DP5), Drosera rotundifolia L. pharmacopuncture 5 % $40{\mu}L$ was injected at right KI3, and formalin 5 % $40{\mu}L$ was injected at right hindpaw 35 minutes later. We analyzed ultrasonic vocalization (USV), Substance P, aspartate aminotransferase(AST), and alanine aminotransferase(ALT). Results : In the early phase of USV, both DP3 and DP5 had an analgesic effect. In the late phase, DP5 had an analgesic effect compared to CON. Substance P in DP5 was significantly decreased compared to CON. In regards to blood AST and ALT, there was no significant difference among NOR, CON, DP3 or DP5. Conclusion : These results suggest that Drosera rotundifolia L. pharmacopuncture helps to reduce formalin-induced pain. It's mechanism is related to substance P, and Drosera rotundifolia L. pharmacopuncture has no influence on liver toxicity.

• 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.

• Animal cells and systems
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• v.16 no.5
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• pp.385-390
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• 2012

The relationship between pain stimulation and the blood glucose level was studied in ICR mice. We examined the possible change of the blood glucose level after the pain stimulation induced by acetic acid injected intraperitoneally (i.p.),, formalin injected subcutaneously (s.c.) into the hind paw, or substance P (SP), glutamate, and proinflammatory cytokines (TNF-${\alpha}$ and IFN-${\gamma}$) injected intrathecally (i.t.). We found in the present study that acetic acid, formalin, SP, TNF-${\alpha}$, and IFN-${\gamma}$ increased the blood glucose level. The blood glucose level reached at maximal state 30 min and returned to normal level 2 h after the pain stimulation in a fasting group. Furthermore, acetic acid, formalin, SP, TNF-${\alpha}$, and IFN-${\gamma}$ caused the elevation of the blood glucose level in D-glucose-fed group only in an additive manner. However, i.t. injection of glutamate did not alter the blood glucose level in a fasting group. In contrast, i.t. injection of glutamate enhanced the blood glucose level in the D-glucose-fed group. Our results suggest that the blood glucose level appears to be differentially regulated by various pain stimulation induced by acetic acid, formalin, SP, glutamate, and pro-inflammatory cytokines.

• 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.

• The Korean Journal of Pain
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• v.18 no.2
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• pp.124-132
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• 2005

Background: This study was performed to evaluate the dose-related effects of naloxone on morphine analgesia in the rat formalin test, and observe the correlation of pain behavior and spinal c-fos expression induced by a formalin injection. Methods: Fifty rats were divided into five groups; control, morphine (morphine pre-treated, intra-peritoneal injection of 0.1 mg of morphine 5 min prior to formalin injection), and three naloxone groups, which were divided according to the administered dose-ratio of naloxone to morphine 20 : 1 ($5{\mu}g$), 10 : 1 ($10{\mu}g$), and 1 : 1 ($100{\mu}g$) representing the low-, medium-, and high-dose naloxone groups, respectively, were injected intra-peritoneally 16 min after a formalin. A fifty ul of 5% formalin was injected into the right hind paw. All rats were observed for their pain behavior according to the number of flinches during phases 1 (2-3, 5-6 min) and 2 (1 min per every 5 min from 10 to 61 min). The spinal c-fos expression was quantitatively analyzed at 1 and 2 hours after the formalin injection using a real-time PCR. Results: The morphine pre-treated (morphine and three naloxone) groups during phase 1, and the morphine, low- and medium-dose naloxone groups during phase 2, showed significantly less flinches compared to those of the control (P < 0.05). In the three naloxone groups, the numbers of flinches were transiently reduced following the naloxone injection in the low- and medium-dose groups compared to those of the morphine group (P < 0.05). The duration of the reduced flinches was longer in the medium-dose group (P < 0.05). The high-dose group revealed immediate increases in flinches immediately after the naloxone injection compared to those of the morphine, low- and medium-dose groups (P < 0.05 for each). The spinal c-fos expression showed no significant patterns between the experimental groups. Conclusions: Our data suggest that relatively low-dose naloxone (1/20 to 1/10 dose-ratio of morphine) transiently potentiates morphine analgesia; whereas, high-dose (equal dose-ratio of morphine) reverses the analgesia, and the spinal c-fos expression does not always correlate with pain behavior in the rat formalin test.

• Journal of dental hygiene science
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• v.14 no.2
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• pp.240-247
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• 2014

Acaiberry (Euterpe oleracea Mart.) is widely diffused in amazon and is known that has high antioxidant capacity and potential anti-inflammatory activities. The aim of this study was to evaluate analgesic effects of acaiberry in formalin-induced orofacial pain through p38 mitogen-activated protein kinases (p38 MAPK) and nicotinamide adenine dinucleotide phosphate 4 (NOX4) pathway. Rats were divided into 5 groups (n=6); formalin (5%, $50{\mu}L$), formalin after saline (vehicle) or acaiberry (16, 80, 160 mg/kg, intraperitoneally). The nociceptive response was investigated all of groups, p38 MAPK or NOX4 were analysed at dose of 80 mg/kg of acaiberry in rat's medulla oblongata and adrenal gland. Results indicated that acai berry produced analgesic effect in a dose-dependent manner and significantly reduced formalin-induced nociceptive response at 15~40 min. Acaiberry (80 mg/kg) decreased the increased p38 MAPK activation and NOX4 expression in medulla oblongata and adrenal gland. Based on these results, acaiberry is believed to be useful for modulation of orofacial pain and its treatments because of its anti-inflammatory and antioxidative effects.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.2
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• pp.143-149
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• 1997

We studied the effects of ginseng protopanaxadiol (PD) and protopanaxatriol (PT) saponins on the analgesia using several pain tests such as writhing, formalin, and tail-flick test. Using mouse, pretreatment of PD or PT saponins (i.p.) induced inhibition of abdominal constrictions caused by 0.9% acetic acid administration(i.p.). The $AD_{50}$ was around 27 (17-43) mg/kg for PD and 13.5 (3-61) mg/kg for PT saponins in writhing test. Both PD and PT saponins also showed the inhibition of bitings and lickings of hindpaw after administration of 1% formalin. In particular, both PD and PT saponins showed analgesic effects on second phase of pain. The $AD_{50}$ was 44.5 (26-76) mg/kg for PD and 105 (55-200) mg/kg for PT saponins in second phase of formalin test. For first phase pain inhibition by PD or PT saponins, they were required higher concentrations. However, PD saponins showed weak analgesic effects in tail-flick test with high concentration. In conclusion, we found that both PD and PT saponins have the analgesic effects in writhing test and second phase of pain in formalin test. These results suggest that both PD and PT saponins inhibit neurogenic or tonic pain rather than acute pain.

• Journal of Acupuncture Research
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• v.33 no.2
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• pp.97-108
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• 2016

Objectives : This study was performed to investigate the analgesic effect of Styrax japonica pharmacopuncture on formalin induced pain in rats and to figure out efficient extraction method. Methods : The subjects were divided into 5 groups ; normal group(treated with normal saline at KI03, and injected normal saline at right hindpaw after 35 minutes), control group(treated with normal saline at KI03, and injected with formalin at right hindpaw after 35 minutes), water group(treated by hot water extraction pharmacopuncture at KI03, and injected with formalin at right hindpaw after 35 minutes), ethanol group(treated with ethanol extraction pharmacopuncture at KI03, and injected with formalin at right hindpaw after 35 minutes), and ultrasound group(treated with ultrasound extraction pharmacacupuncture and injected with fromalin formalin at right hindpaw after 35 minutes). We conducted a formalin test with ultrasonic vocalization( USV), and after the test checked for substance P, Aspartate aminotransferase(AST), and Alanine aminotransferase(ALT) concentration in the blood for each of the groups. Results : There was a significant analgesic effect of Styrax japonica pharmacopuncture in the early phase of the formalin test, and pharmacopuncture made with an ultrasound extracting method was observed to have a better analgesic effect than other extracting methods in early phases. The substance P concentration decreased significantly in the Styrax japonica pharmacopuncture treated group and no difference was found in the AST and ALT concentration of each group. Conclusion : These results demonstrated that Styrax japonica pharmacopuncture had analgesic effects in noxious nociceptors stimulation. Also pharmacopuncture made with an ultrasound extracting method had a better analgesic effect than others.

• Archives of Pharmacal Research
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• v.28 no.2
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• pp.227-231
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• 2005

We examined the effect of the subcutaneous (s.c.) pretreatment of formalin into both hind paws of mice on the antinociception induced by the intracerebroventricularly (i.c.v.) or intrathecally (i.t.) administration of ${\beta}$-endorphin using the tail-flick test. Pretreatment with formalin ($5\%$) for 5 h had no affect on the i.c.v. administered ${\beta}$-endorphin-induced tail-flick response. However, pretreatment with formalin for 40 h attenuated the tail-flick inhibition induced by i.c.v. administered ${\beta}$-endorphin. This antinociceptive tolerance to i.c.v. ${\beta}$-endorphin continued up to 1 week, but to a lesser extent. Pretreatment with formalin for 5 and 40 h significantly reduced the i.t. ${\beta}$-endorphin-induced inhibition of the tail-flick response, which continued up to 1 week. The s.c. formalin treatment increased the hypothalamic pro-opiomelanocortin (POMC) mRNA level at 2 h, but this returned to the basal level after 40 h. Our results suggest that the increase in the POMC mRNA level in the hypothalamus appears to be involved in the supraspinal or spinal ${\beta}$-endorphin-induced antinociceptive tolerance in formalin-induced inflammatory pain.