Antinociceptive Effects of Ginsenoside Rg3 in a Rat Model of Incisional Pain

2016 ◽  
Vol 57 (3-4) ◽  
pp. 211-223 ◽  
Author(s):  
Eun Jin Ahn ◽  
Geun Joo Choi ◽  
Hyun Kang ◽  
Chong Wha Baek ◽  
Yong Hun Jung ◽  
...  
Keyword(s):  
Analgesic Effect ◽  
Control Group ◽  
Ginsenoside Rg3 ◽  
Dose Response Relationship ◽  
Withdrawal Threshold ◽  
Antinociceptive Effects ◽  
Plantar Incision ◽  
Incisional Pain ◽  
Von Frey Filaments ◽  
Inflammatory Effect

Background: Ginsenoside Rg3 is an extract of total ginseng saponins, which accounts for 4.7% of all saponins. This study aimed to identify the mechanisms of the antinociceptive effects of ginsenoside Rg3. Methods: Rats were randomly divided into six groups, which were treated with vehicle or 0.5, 1, 1.5, 2, or 4 mg/kg of ginsenoside Rg3 intraperitoneally 2 h after a plantar incision was made. To evaluate the mechanisms of antinociceptive effects, the rats were intraperitoneally injected with naloxone 5 mg/kg, atropine 1 mg/kg, yohimbine 2 mg/kg, mecamylamine 1 mg/kg, prazosin 1 mg/kg, and dexmedetomidine 5 μg/kg. Hyperalgesia produced by the plantar incision was assessed using von Frey filaments 1 day before the incision (BI) and 2 h after the plantar incision (AP); this measurement was repeated at 15, 30, 45, 60, 80, 100 and 120 min, and 24 and 48 h after the injection of ginsenoside Rg3. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were measured 1 day before incision and 120 min, 24 h, and 48 h after the injection of ginsenoside Rg3 or vehicle. Results: The mechanical withdrawal threshold (MWT) significantly increased in the group that received ginsenoside Rg3. The dose-MWT response showed a curvilinear, bell-shaped relationship. The maximum MWT was found with the administration of ginsenoside Rg3 at 1.5 mg/kg; MWT decreased to 2 and 4 mg/kg. Yohimbine diminished the analgesic effect of ginsenoside Rg3. Prazosin and dexmedetomidine increased the analgesic effect of ginsenoside Rg3. IL-1β and IL-6 appeared significantly lower relative to control group. Conclusions: Ginsenoside Rg3 has an analgesic effect with a curvilinear dose-response relationship. Alpha 2 adrenergic receptor appeared to be related to the analgesic effect of ginsenoside Rg3. Also, the anti-inflammatory effect of ginsenoside Rg3 could be related to its analgesic effect.

scholarly journals Frozen Vein Wrapping for Chronic Nerve Constriction Injury Reduces Sciatic Nerve Allodynia in a Rat Model

2021 ◽  
Author(s):  
Michiaki Mukai ◽  
Kentaro Uchida ◽  
Naoya Hirosawa ◽  
Kenichi Murakami ◽  
Gen Inoue ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Injury ◽  
Donor Site ◽  
Operation Time ◽  
Donor Site Morbidity ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Autologous Vein ◽  
Withdrawal Threshold ◽  
Von Frey Filaments

Abstract BackgroundAutologous vein wrapping (VW) is used in the treatment of recurrent chronic constriction neuropathy and traumatic peripheral nerve injury. However, use of autologous veins is limited by the inability to obtain longer veins of sufficient length for larger sites. Frozen allograft tissue has several advantages, including its availability for large grafts, avoidance of donor-site morbidity, and shorter operation time. Here, we investigated the effect of frozen vein wrapping (FVW) in Wistar rats as a model of sciatic nerve injury. MethodsThe rats were grouped by treatment as (i) untreated after chronic constriction injury surgery (CCI; control group), (ii) treated with vein wrapping using freshly isolated vein (VW), and (iii) treated with vein wrapping using frozen vein (FVW). Mechanical allodynia was assessed with von Frey filaments on postoperative days (PODs) 1, 3, 5, 7, and 14. ResultsThe response of heme oxygenase-1 gene, Hmox-1, expression to VW and FVW was assessed by RT-PCR. Both VW and FVW significantly increased withdrawal threshold levels compared to the untreated control group on POD 1, 3, and 5. Both VW and FVW also showed increased HO-1 expression compared to the CCI group. ConclusionsOur results suggest that FVW may be a suitable therapeutic optionas a source of large grafts.

scholarly journals Effect of AMG0347, a Transient Receptor Potential Type V1 Receptor Antagonist, and Morphine on Pain Behavior after Plantar Incision

2008 ◽  
Vol 108 (6) ◽  
pp. 1100-1108 ◽  
Author(s):  
Chaoran Wu ◽  
Narender R. Gavva ◽  
Timothy J. Brennan
Keyword(s):  
Pain Score ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Withdrawal Threshold ◽  
Withdrawal Latency ◽  
Trpv1 Receptors ◽  
Plantar Incision ◽  
Transient Receptor ◽  
Incisional Pain ◽  
Heat Hyperalgesia

Background Studies on postoperative pain examine the etiology of incisional pain with the goal to develop new treatments for patients' pain after surgery. The current study examined the analgesic effects of a recently developed transient receptor potential vanilloid 1 (TRPV1) antagonist, AMG0347, on incisional pain in rats. Doses of morphine lower than those used in most rodent studies were also examined. Methods Adult Sprague-Dawley rats were underwent plantar incision. The effect of either AMG0347 or morphine was tested for its effects on guarding pain score, heat withdrawal latency, and mechanical withdrawal threshold. AMG0347 was also tested against nociceptive behaviors caused by capsaicin. Results For incisional pain, AMG0347 did not change the withdrawal threshold to mechanical stimulation or the guarding pain score. The withdrawal latency to heat increased from 3 h through 1 day after AMG0347 administration. AMG0347 prevented the decreases in heat withdrawal latency and mechanical withdrawal threshold caused by capsaicin infiltration and prevented the increase in activity caused by intrathecal capsaicin injection. Doses of morphine less than 1 mg/kg inhibited both the guarding and heat hyperalgesia; only the 1-mg/kg does affected mechanical responses. Conclusions AMG0347 decreased capsaicin-induced heat and mechanical hyperalgesia and blocked central TRPV1 receptors. AMG0347 only decreased heat hyperalgesia after plantar incision even though both peripheral and central TRPV1 receptors were blocked. The smallest doses of morphine affected guarding pain and heat responses.

scholarly journals L-Arginine-No System Participates in the Analgesic Effect of Flunixin Meglumine in the Rat

2016 ◽  
Vol 66 (1) ◽  
pp. 103-114 ◽  
Author(s):  
Mirjana Milovanović ◽  
Sonja Vučković ◽  
Milica Prostran ◽  
Saša Trailović ◽  
Milan Jovanović
Keyword(s):  
Methyl Ester ◽  
Effective Dose ◽  
Analgesic Effect ◽  
Antinociceptive Effect ◽  
Painful Stimulus ◽  
Withdrawal Threshold ◽  
Flunixin Meglumine ◽  
Antinociceptive Effects ◽  
Pre Treatment

AbstractThis study investigated whether the L-arginine-NO system participates in the analgesic effect of flunixin meglumine in the rat. Hyperalgesia was induced by intraplantar (i.pl.) administration of carrageenan (500 μg) into the rat’s hind paw. Electronic von Frey apparatus was used to determine paw withdrawal threshold induced by pressure as the painful stimulus, measured in grams (g). Flunixin meglumine (FM; 0.09-0.1 mg/kg; s.c.) and NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg; i.p.), given separately as a pre-treatment, i.e. 15 min before i.pl. injection of carrageenan, produced a significant antinociception. When FM (0.09 mg/kg) and a sub-effective dose of L-NAME (5 mg/kg) were co-administered, the antinociceptive effect was significantly increased in comparison with the effect of FM alone. L-arginine (L-ARG;10 mg/kg; i.p.) itself did not produce significant effect on carrageenan-induced hyperalgesia, but significantly reduced the antinociceptive effects of both FM and FM + L-NAME combination. The inhibition of the production of NO might be involved in the mechanism of the analgesic effect of FM.

scholarly journals Osmotically balanced, large unilamellar liposomes that enable sustained bupivacaine release for prolonged pain relief in in vivo rat models

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hyebin Yoo ◽  
Jun Seok Park ◽  
Seung Soo Oh ◽  
Hyun Kang
Keyword(s):  
Postoperative Pain ◽  
In Vitro Release ◽  
Cost Effective ◽  
Control Group ◽  
Sprague Dawley ◽  
Liposomal Bupivacaine ◽  
Withdrawal Threshold ◽  
Incisional Pain

AbstractTo efficiently prolong analgesic effects, we developed osmotically balanced, large unilamellar liposomes (~ 6 μm in diameter) in which highly concentrated bupivacaine (up to 30 mg/mL) was encapsulated, and their sustained bupivacaine release was highly effective in relieving postoperative pain over 24 h in a rat model. Our reverse-phase evaporation method based on non-toxic alcohol, ethanol, enabled simple and cost-effective production of bupivacaine-loaded liposomes, of which osmotic pressure was readily balanced to improve the structural stability of the enlarged unilamellar liposomes along with extension of their shelf life (> a month). The in vitro release profile verified that the release duration of the bupivacaine-loaded liposomes extended up to 6 days. For the in vivo study, male Sprague–Dawley rats were used for the incisional pain model, simulating postoperative pain, and the mechanical withdrawal threshold (MWT) was measured using a von Frey filament. Compared to the control group that received intraplantar administration of normal saline, the group of liposomal bupivacaine showed that the initially increased MWT gradually decreased up to 24 h, and importantly, the analgesic effect of the liposomal bupivacaine was maintained 6 times longer than that of bupivacaine only, proving the potential of effective long-acting anesthetics.

scholarly journals Osmotically Balanced, Large Unilamellar Liposomes for Sustained Bupivacaine Release: From the Development of Liposomes to Their in Vivo Application

2021 ◽  
Author(s):  
Hyebin Yoo ◽  
Jun Seok Park ◽  
Seung Soo Oh ◽  
Hyun Kang
Keyword(s):  
Postoperative Pain ◽  
In Vitro Release ◽  
Cost Effective ◽  
Control Group ◽  
Sprague Dawley ◽  
Liposomal Bupivacaine ◽  
Withdrawal Threshold ◽  
Incisional Pain

Abstract To efficiently prolong analgesic effects, we developed osmotically balanced, large unilamellar liposomes (~6 μm in diameter) in which highly concentrated bupivacaine (up to 30 mg/mL) was encapsulated, and their sustained bupivacaine release was highly effective in relieving postoperative pain over 24 h in a rat model. Our reverse-phase evaporation method based on non-toxic alcohol, ethanol, enabled simple and cost-effective production of bupivacaine-loaded liposomes, of which osmotic pressure was readily balanced to improve the structural stability of the enlarged unilamellar liposomes along with extension of their shelf life (> a month). The in vitro release profile verified that the release duration of the bupivacaine-loaded liposomes extended up to six days. For the in vivo study, male Sprague-Dawley rats were used for the incisional pain model, simulating postoperative pain, and the mechanical withdrawal threshold (MWT) was measured using a von Frey filament. Compared to the control group that received intraplantar administration of normal saline, the group of liposomal bupivacaine showed that the initially increased MWT gradually decreased up to 24 h, and importantly, the analgesic effect of the liposomal bupivacaine was maintained 6 times longer than that of bupivacaine only, proving the potential of effective long-acting anesthetics.

The Effect of Fluoxetine and Ibuprofen on BCG-Induced Alteration in Pain Sensitivity in Mice

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Heba H El-Morsy ◽  
Wesam El-Bakly ◽  
Amany H Hasanin ◽  
May Hamza ◽  
M Abdel-Bary
Keyword(s):  
Drinking Water ◽  
Mechanical Allodynia ◽  
Formalin Test ◽  
Forced Swim Test ◽  
Tail Suspension Test ◽  
Control Group ◽  
Base Line ◽  
Immobility Time ◽  
Long Time ◽  
Incisional Pain

Abstract Clinical observations recognized the co-existence and interactions of pain and depression a long time, ago. The aim of this work was to study the effect of ibuprofen and fluoxetine on BCGinduced depressive-like behaviour, on formalin-induced pain, as well as on mechanical allodynia after planter incision in mice. BCG induced a depressive behaviour that was seen in the forced swim test (FST) and the tail suspension test (TST). It also induced a decrease in pain-related behaviour in the formalin test, and an increase in the baseline in mechanical allodynia test compared to the control group. Fluoxetine (80 mg/L of drinking water) showed a significant decrease in the immobility time in the FST and TST and enhanced pain related behaviour in formalin test in the BCG-inoculated group. However, it did not affect the increase in the pain threshold in the planter incision allodynia model. Adding ibuprofen to drinking water (0.2 g/L of drinking water), reversed the depressive like behaviour induced by BCG and enhanced pain-related behaviour in formalin test, in both the total pain-related behaviour and phase 2. It also prevented the increase in the base line induced by BCG. On the other hand, the incisional pain model was not affected by BCG inoculation except at the 2-hour time point, where it showed hypoalgesia, as well.

Inhibitory Effects of Indomethacin on Implantation and its Related Phenomena

1996 ◽  
Vol 24 (4) ◽  
pp. 358-362 ◽  
Author(s):  
K Kanayama ◽  
H Osada ◽  
K Nariai ◽  
T Endo
Keyword(s):  
Birth Rate ◽  
Inhibitory Effect ◽  
High Rate ◽  
Control Group ◽  
Corpora Lutea ◽  
Response Relationship ◽  
Inhibitory Effects ◽  
Dose Response Relationship ◽  
Dose Dependent ◽  
Implantation Period

The dose-response relationship for the inhibitory effect of indomethacin on implantation and continuance of pregnancy was examined in four groups of rabbits administered with indomethacin (2.5, 5.0, 7.5 and 10.0 mg/kg) during the implantation period and compared with a control group. Implanted fetuses and corpora lutea were counted by laparotomy, and the number of offspring born was noted. The inhibitory effect of indomethacin on implantation was found to be dose–dependent, and the birth rate decreased in the indomethacin groups compared with the control group. As a result, even where implantation had been achieved, death of the implanted fetuses occurred at a high rate in rabbits administered with indomethacin during the implantation period.

Postoperative analgesia by adding acupuncture to conventional therapy, a non-randomized controlled trial

2018 ◽  
Vol 16 (2) ◽  
Author(s):  
Ilana Levy ◽  
Samuel Attias ◽  
Lior Cohen ◽  
Nadav Stoppelmann ◽  
Dan Steinberger ◽  
...  
Keyword(s):  
Side Effects ◽  
Postoperative Pain ◽  
Analgesic Effect ◽  
Pain Treatment ◽  
Standard Of Care ◽  
Acupuncture Group ◽  
Controlled Study ◽  
Control Group ◽  
Pain Level ◽  
Randomized Controlled

Abstract Background Postoperative pain is common in patients hospitalized in surgical departments, yet it is currently not sufficiently controlled by analgesics. Acupuncture, a complementary medical practice, has been evaluated for its benefits in postoperative pain with heterogeneous results. We tested the feasibility of a controlled study comparing the postoperative analgesic effect of acupuncture together with standard-of-care to standard-of-care only. Methods In this pilot non-randomized controlled study conducted at a tertiary medical center in Israel, patients received either acupuncture with standard-of-care pain treatment (acupuncture group) or standard-of-care treatment only (control group) following surgery. Visual Analogue Scale (VAS) ratings for pain level at rest and in motion were evaluated both at recruitment and two hours after treatment. Acupuncture-related side effects were reported as well. Results We recruited 425 patients; 336 were assigned to the acupuncture group and 89 to the control group. The acupuncture group exhibited a decrease of at least 40% in average level of pain both at rest (1.8±2.4, p<0.0001) and in motion (2.1±2.8, p<0.0001) following acupuncture, whereas the control group exhibited no significant decrease (p=0.92 at rest, p=0.98 in motion). Acupuncture's analgesic effect was even more prominent in reducing moderate to severe pain at baseline (VAS ≥4), with a decrease of 49% and 45% of pain level at rest and in motion respectively (p<0.001), compared with no significant amelioration in the control group (p=0.20 at rest, p=0.12 in motion). No major side effects were reported. Conclusion Integrating acupuncture with standard care may improve pain control in the postoperative setting.

scholarly journals Galanin Receptor 2 Is Involved in Galanin-Induced Analgesic Effect by Activating PKC and CaMKII in the Nucleus Accumbens of Inflammatory Pain Rats

2021 ◽  
Vol 14 ◽  
Author(s):  
Mengnan Li ◽  
Xiaomin Zhang ◽  
Chongyang Li ◽  
Yanan Liu ◽  
Shuang Yang ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Protein Kinase ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Signaling Mechanism ◽  
Withdrawal Threshold ◽  
Calcium Calmodulin Dependent ◽  
Kinase C ◽  
Dependent Protein ◽  
Galanin Receptors

It has been reported that galanin has an analgesic effect via activating galanin receptors (GALRs). This study focused on the involvement of GALR2 in the galanin-induced analgesic effect and its signaling mechanism in the nucleus accumbens (NAc) of inflammatory rats. Animal models were established through injecting carrageenan into the plantar of rats’ left hind paw. The results showed that GALR2 antagonist M871 weakened partially the galanin-induced increases in hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation in NAc of inflammatory rats. Moreover, the GALR2 agonist M1145 prolonged the HWL and HWT, while M871 blocked the M1145-induced increases in HWL and HWT. Western blotting showed that the phosphorylation of calcium/calmodulin-dependent protein kinase II (p-CaMKII) and protein kinase C (p-PKC) in NAc were upregulated after carrageenan injection, while p-PKC and p-CaMKII were downregulated after intra-NAc administration of M871. Furthermore, the CaMKII inhibitor KN93 and PKC inhibitor GO6983 attenuated M1145-induced increases in HWL and HWT in NAc of rats with inflammatory pain. These results prove that GALR2 is involved in the galanin-induced analgesic effect by activating CaMKII and PKC in NAc of inflammatory pain rats, implying that GALR2 agonists probably are potent therapeutic options for inflammatory pain.

scholarly journals EVALUATION OF ANALGESIC ACTIVITY OF MURRAYA KOENIGII AND CORIANDRUM SATIVUM LEAVES EXTRACT IN ANIMAL MODEL.

2018 ◽  
Vol 11 (1) ◽  
pp. 328
Author(s):  
Kartik Salwe J ◽  
Mirunalini R ◽  
Jervin Mano ◽  
Manimekalai K
Keyword(s):  
Analgesic Activity ◽  
Analgesic Effect ◽  
Coriandrum Sativum ◽  
Control Group ◽  
Tail Flick ◽  
Murraya Koenigii ◽  
Hot Plate ◽  
Plate Method ◽  
Standard Drug ◽  
Soxhlet Apparatus

 Objective: The objective of the study was to investigate the analgesic activity of hydroalcoholic extract of Murraya koenigii and Coriandrum sativum leaves and compared it with standard drug in an animal model.Methods: Hydroalcoholic extracts of M. koenigii and C. sativum leaves were obtained using Soxhlet apparatus. The central analgesic property was screened by hot plate method in mice and tail flick method in rats. The pain reaction time (PRT) was measured at 30, 60, and 120 min. The peripheral analgesic activity was evaluated by acetic acid induced writhing in mice.Results: In hot plate method M. koenigii leaves extract at both doses and tramadol showed significant increase in PRT at 30, 60, and 120 min compared with control group. C. sativum leaves extract showed significant increase in PRT only at 60 and 120 min compared to control group. In tail flick method M. koenigii leaves extract at both doses, higher dose of C. sativum leaves extract and tramadol showed significant increase in PRT at 30, 60, and 120 min compared with control group. Higher dose of M. koenigii leaves extract (200 mg/kg) was comparable with standard drug tramadol in both the methods. M. koenigii leaves extract at both dose showed significant reduction in the number of writhing but C. sativum leaves extract failed to show any significant reduction in the number of writhing compared with control. Higher dose of M. koenigii leaves extract was comparable with standard drug tramadol.Conclusion: M. koenigii leaves extract showed both peripheral and central analgesic effect while C. sativum leaves extract showed only peripheral analgesic effect.

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