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.

Orofacial antinociceptive effect of the ethanolic extract of Annona vepretorum Mart. (Annonaceae)

2016 ◽  
Vol 71 (7-8) ◽  
pp. 209-214 ◽  
Author(s):  
Juliane C. Silva ◽  
Larissa A.R.O. Macedo ◽  
Grasielly R. Souza ◽  
Raimundo G. Oliveira-Junior ◽  
Sarah R.G. Lima-Saraiva ◽  
...  
Keyword(s):  
Orofacial Pain ◽  
Antinociceptive Effect ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Upper Lip ◽  
Antinociceptive Effects ◽  
Rubbing Behavior ◽  
Pre Treatment ◽  
The Right ◽  
Orofacial Nociception

Abstract Annona vepretorum Mart. (Annonaceae) is a species popularly known in Brazil as “araticum” and “pinha da Caatinga”. We have evaluated the antinociceptive effects of A. vepretorum in formalin-, capsaicin-, and glutamate-induced orofacial nociception in mice. Male Swiss mice were pretreated with either saline (p.o.), A. vepretorum ethanol extract (Av-EtOH 25, 50 and 100 mg/kg, p.o.), or morphine (10 mg/kg, i.p.), before formalin, capsaicin, or glutamate was injected into the right upper lip. Pre-treatment with Av-EtOH at all doses produced a reduction in face-rubbing behavior induced by formalin in both phases, and these pre-treatments also produced a significant antinociceptive effect in the capsaicin and glutamate tests. Pre-treatment with naloxone (1.5 mg/kg, i.p.) did not reverse the antinociceptive activity of the extract at the dose of 100 mg/kg in the first phase of this test. Our results suggest that Av-EtOH might be useful in the treatment of orofacial pain.

scholarly journals Antinociceptive effects of intrathecal cimifugin treatment: a preliminary rat study based on formalin test

2020 ◽  
Vol 15 (4) ◽  
pp. 478-485
Author(s):  
Hyun Young Lee ◽  
Young Joon Ki ◽  
Su Yeong Park ◽  
Soo Yeon Cho ◽  
Jinyoung Seo ◽  
...  
Keyword(s):  
Analgesic Effect ◽  
Formalin Test ◽  
Phase 1 ◽  
Antinociceptive Effect ◽  
Intrathecal Administration ◽  
Phase 2 ◽  
Sprague Dawley ◽  
Antinociceptive Effects ◽  
Saposhnikovia Divaricata ◽  
Rat Study

Background: Cimifugin is one of the components of the root of Saposhnikovia divaricata. The extract derived from S. divaricata is traditionally used as an analgesic. This study was conducted to evaluate the analgesic effect of intrathecal cimifugin in the formalin test.Methods: Male Sprague–Dawley rats (n = 20) were randomized into four groups for intrathecal administration of 70% dimethylsulfoxide and various doses of cimifugin (100 μg, 300 μg, and 1,000 μg). The typical flinch response after the injection of 5% formalin into the hind paw was assessed in two distinct phases: phase 1 until 10 min, and phase 2 from 10 min to 60 min. ED50 values were calculated via linear regression.Results: Intrathecal cimifugin significantly reduced the flinch response in both phases of the formalin test. Significant antinociceptive effects of cimifugin were found with the dose of 300 μg in phase 1 and the dose of 100 μg in phase 2. The ED50 value (95% confidence intervals) of intrathecal cimifugin was 696.1 (360.8–1,342.8) μg during phase 1 and 1,242.8 (42.0–48,292.5) μg during phase 2.Conclusions: Intrathecal cimifugin has an antinociceptive effect against formalin-induced pain. Cimifugin has an anti-inflammatory effect at low concentrations, and non-inflammatory analgesic effect at higher concentrations.

scholarly journals Study on the Antinociceptive Effects of Herba Epimedium in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Jiang-hong Sun ◽  
Xin-jie Ruan ◽  
Li-na Wang ◽  
Shuang Liang ◽  
Xin-ping Li
Keyword(s):  
Nervous System ◽  
Analgesic Effect ◽  
Partial Agonist ◽  
Antinociceptive Effect ◽  
Blocking Agent ◽  
Peripheral Region ◽  
Hot Plate ◽  
Antinociceptive Action ◽  
Antinociceptive Effects ◽  
Long Time

The present study was conducted to investigate the antinociceptive action of relationship between Herba Epimedium (HE) and5-HT1Areceptor, between Herba Epimedium (HE) and5-HT2Areceptor. We used the hot-plate method and the writhing assay in mice by the intracerebroventricular (i.c.v.) injection and observed the analgesic effect of HE. Furthermore, through the i.c.v. injection,5-HT1Areceptor partial agonist Buspirone, antagonist Propranolol, the adrenalineβ1-receptor selective blocking agent Metoprolol, and5-HT2Areceptor agonist hydrochloride DOI and antagonist Ketanserin were used, and, 5 min later, HE was used to investigate the impacts of drugs on the analgesic effect in the same way. Results showed that HE had fast and significant antinociception in nervous system, and the effects can persist for a long time. Buspirone and Hydrochloride DOI can remarkably increase the antinociception of HE in nervous system. Ketanserin leads to a significant decrease in its antinociception in nervous system; Metoprolol also has antinociceptive action in nervous system, but it can inhibit the antinociceptive effect of Herba Epimediumin peripheral region. These results suggest that HE has significant antinociception effect and its mechanism is related with5-HT1Areceptor,5-HT2Areceptor, and adrenalineβ1-receptor.

scholarly journals Opioid Mechanism Involvement in the Synergism Produced by the Combination of Diclofenac and Caffeine in the Formalin Model

ISRN Pain ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
José María Flores-Ramos ◽  
M. Irene Díaz-Reval
Keyword(s):  
Oral Administration ◽  
Effective Dose ◽  
Analgesic Effect ◽  
Antinociceptive Effect ◽  
Dependent Effect ◽  
Opioid Mechanisms ◽  
Dose Dependent ◽  
Dose Dependent Effect ◽  
Central Level

Analgesics can be administered in combination with caffeine for improved analgesic effectiveness in a process known as synergism. The mechanisms by which these combinations produce synergism are not yet fully understood. The aim of this study was to analyze whether the administration of diclofenac combined with caffeine produced antinociceptive synergism and whether opioid mechanisms played a role in this event. The formalin model was used to evaluate the antinociception produced by the oral administration of diclofenac, caffeine, or their combination. Opioid involvement was analyzed through intracerebroventricular (i.c.v.) administration of naloxone followed by the oral administration of the study drugs. Diclofenac presented a dose-dependent effect, with a mean effective dose (ED50) of 6.7 mg/kg. Caffeine presented an analgesic effect with a 17–36% range. The combination of subeffective doses of each of the two drugs presented the greatest synergism with an effect of 57.7 ± 5.6%. The maximal antinociceptive effect was obtained with the combination of 10.0 mg/kg diclofenac and 1.0 mg/kg of caffeine, with an effect of 76.7 ± 5.6%. The i.c.v. administration of naloxone inhibited the effect of diclofenac, both separately and combined. In conclusion, caffeine produces antinociceptive synergism when administered in combination with diclofenac, and this synergism is partially mediated by opioid mechanisms at the central level.

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 The synergistic antinociceptive effect of lornoxicam in combination with tramadol

2013 ◽  
Vol 3 (3) ◽  
pp. 238-242
Author(s):  
Amela Saračević ◽  
Fahir Bečić
Keyword(s):  
Analgesic Effect ◽  
Opioid Analgesic ◽  
Antinociceptive Effect ◽  
Subcutaneous Administration ◽  
Opioid Analgesics ◽  
Antinociceptive Effects ◽  
Significant Difference ◽  
Specific Receptors ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Introduction: One of the most important priorities in therapy is pain control. Therefore, many different groups of drugs are being used for this purpose, primarily opioid analgesics and non-steroidal anti-inflammatory drugs (NSAIDs). Opioid analgesic tramadol, by binding to specific receptors, modulates the perception and response to painful stimuli and inhibits transmitting and further processing of pain impulses. Lornoxicam, which belongs to the oxicam class of NSAIDs, is a non-selective cyclooxygenase inhibitor with strong analgesic and anti-inflammatory effects, and better tolerance profile. Preliminary research, which requires further verification, suggests that lornoxicam may be a better alternative or adjunctive therapy to opioid analgesics in the treatment of moderate to severe pain. The aim of this study was to investigate antinociceptive effects of lornoxicam, as well as the combination of lornoxicam with tramadol.Methods: Analgesic effect of combination of lornoxicam and tramadol or lornoxicam applied alone was examined on female albino mice, using a hot plate method. Measurements were made 30, 60, 90 and 120 minutes after intraperitoneal and subcutaneous administration, in dose of 10 mg/kg.Results: Combination of lornoxicam and tramadol, applied intraperitoneally, increases the threshold of sensitivity to painful stimuli, which was not the case with subcutaneous administration.Conclusions: Lornoxicam significantly increases analgesic effect when applied intraperitoneally in combination with tramadol. On the other hand, lornoxicam in combination with tramadol, did not increase the threshold of sensitivity to painful stimuli with significant difference, after subcutaneous administration

Antinociceptive effect of melatonin in the animal model of Parkinson’s Disease

2021 ◽  
Vol 4 (3) ◽  
pp. 440-452
Author(s):  
Tahsine Kosksi ◽  
Arem Selmi ◽  
Sahar Mani ◽  
Mriem Ben Rhouma ◽  
Sana Boughammoura ◽  
...  
Keyword(s):  
Animal Model ◽  
Mechanical Allodynia ◽  
Medial Forebrain Bundle ◽  
Antinociceptive Effect ◽  
Melatonin Treatment ◽  
Withdrawal Threshold ◽  
Melatonin Administration ◽  
Antinociceptive Effects ◽  
6 Hydroxydopamine ◽  
Antiallodynic Effect

Several animal experimental and clinical studies have shown the effectiveness of melatonin in the treatment of some symptoms of Parkinson's disease (PD). However, the antinociceptive effect of melatonin against pain associated to PD has not been fully investigated. Thus, the present study investigated the possible antiallodynic and antinociceptive effects of acute and chronic melatonin treatments in Parkinsonian model of rats. This model was created by unilateral injection of 6-hydroxydopamine (6-OHDA) into the left medial forebrain bundle (MFB). The electronic von Frey test was used to analyze the antiallodynic effect of melatonin on this PD animal model. In addition, c-Fos immunostaining was also used as a marker of nociception to evaluate the neuronal activity related to the nociception processing. The results showed that unilateral injection of 6-OHDA induced a significant decrease in paw withdrawal threshold in both ipsilateral and contralateral paws, which indicate mechanical allodynia induction. This allodynia was transitorily reversed by apomorphine as a dopamine agonist. Melatonin treatment significantly increased threshold of allodynia. Melatonin administration of both acutely or chronically significantly downregulated the c-Fos expression of neurons in 6-OHDA treated animals. In conclusion, 6-OHDA treatment can induces a bilateral mechanical hypernociception in rats while melatonin treatment produces profound antinociceptive effect. This finding paves the way to use melatonin as an antinociceptive agent for PD clinically.

scholarly journals Aristolochia trilobata: Identification of the Anti-Inflammatory and Antinociceptive Effects

Biomedicines ◽  
2020 ◽  
Vol 8 (5) ◽  
pp. 111
Author(s):  
Dayana da Costa Salomé ◽  
Natália de Morais Cordeiro ◽  
Tayná Sequeira Valério ◽  
Darlisson de Alexandria Santos ◽  
Péricles Barreto Alves ◽  
...  
Keyword(s):  
Enzyme Inhibitor ◽  
Interleukin 1 ◽  
Antinociceptive Effect ◽  
Cholinergic Receptor ◽  
Hot Plate ◽  
Nitric Oxide Synthase Inhibitor ◽  
Antinociceptive Effects ◽  
Anti Inflammatory ◽  
Skin Affection ◽  
Synthase Inhibitor

Aristolochia trilobata, popularly known as “mil-homens,” is widely used for treatment of stomach aches, colic, asthma, pulmonary diseases, diabetes, and skin affection. We evaluated the antinociceptive and anti-inflammatory activities of the essential oil (EO) and the main constituent, 6-methyl-5-hepten-2-yl acetate (sulcatyl acetate, SA). EO and SA (1, 10, and 100 mg/kg, p.o.) were evaluated using chemical (formalin-induced licking) and thermal (hot-plate) models of nociception or inflammation (carrageenan-induced cell migration into the subcutaneous air pouch, SAP). The mechanism of antinociceptive activity was evaluated using opioid, cholinergic receptor antagonists (naloxone and atropine), or nitric oxide synthase inhibitor (L-NAME). EO and SA presented a central antinociceptive effect (the hot-plate model). In formalin-induced licking response, higher doses of EO and SA also reduced 1st and 2nd phases. None of the antagonists and enzyme inhibitor reversed antinociceptive effects. EO and SA reduced the leukocyte migration into the SAP, and the cytokines tumor necrosis factor and interleukin-1 (TNF-α and IL-1β, respectively) produced in the exudate. Our results are indicative that EO and SA present peripheral and central antinociceptive and anti-inflammatory effects.

scholarly journals The activation of galanin receptor 2 plays an antinociceptive effect in nucleus accumbens of rats with neuropathic pain

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Yan Dong ◽  
Chong-Yang Li ◽  
Xiao-Min Zhang ◽  
Ya-Nan Liu ◽  
Shuang Yang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nucleus Accumbens ◽  
Pain Threshold ◽  
Antinociceptive Effect ◽  
Galanin Receptor ◽  
Pain Model ◽  
Withdrawal Threshold ◽  
Neuropathic Pain Model ◽  
Galanin Receptors ◽  
Intact Rats

AbstractOur previous research has shown that galanin plays an antinociceptive effect via binding to galanin receptors (GalRs) in nucleus accumbens (NAc). This study focused on the involvement of GalR2 in galanin-induced antinociceptive effect in NAc of neuropathic pain rats. The chronic constriction injury of sciatic nerve (CCI) was used to mimic neuropathic pain model. The hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation were measured as the indicators of pain threshold. The results showed that 14 and 28 days after CCI, the expression of GalR2 was up-regulated in bilateral NAc of rats, and intra-NAc injection of GalR2 antagonist M871 reversed galanin-induced increases in HWL and HWT of CCI rats. Furthermore, intra-NAc injection of GalR2 agonist M1145 induced increases in HWL and HWT at day 14 and day 28 after CCI, which could also be reversed by M871. Finally, we found that M1145-induced antinociceptive effect in NAc of CCI rats was stronger than that in intact rats. These results imply that the GalR2 is activated in the NAc from day 14 to day 28 after CCI and GalR2 is involved in the galanin-induced antinociceptive effect in NAc of CCI rats.

scholarly journals Clinical, behavioral and antinociceptive effects of crotalphine in horses

2015 ◽  
Vol 46 (4) ◽  
pp. 694-699
Author(s):  
Erica Cristina Bueno do Prado Guirro ◽  
João Henrique Perotta ◽  
Márcio de Paula ◽  
Yara Cury ◽  
Carlos Augusto Araújo Valadão
Keyword(s):  
Inflammatory Pain ◽  
Antinociceptive Effect ◽  
Behavioral Changes ◽  
Behavioral Effects ◽  
Phase Iii ◽  
Intact Skin ◽  
Kappa Opioid ◽  
Antinociceptive Effects ◽  
Analgesic Peptide ◽  
Scapular Region

ABSTRACT: Crotalphine is a novel analgesic peptide that acts on kappa opioid and delta receptors, causing powerful analgesia in rats submitted to inflammatory, neuropathic or oncologic models of pain. This study evaluated clinical, behavioral and antinociceptive effects caused by crotalphine in horses, employing 18 Arabian horses and it was divided in three phases. In Phase I, "clinical and behavioral effects", crotalphine did not change the latency to urinate and defecate; did not modify the values of cardiac or respiratory rates, intestinal motility and rectal temperature; and did not cause significant ataxia, head, eye and lip ptosis. In Phase II, "antinociceptive effect on intact skin at scapular or ischial region", crotalphine did not cause significant analgesia. In Phase III, "antinociceptive effect on incised skin at scapular or ischial region", crotalphine promoted effective antinociceptive effects for six hours and inhibited hyperalgesia state for three days in the ischial region of horses submitted to incisional model of inflammatory pain, but crotalphine did not evoke relevant analgesic effect on the scapular region. Concluding, intravenous injection of a single dose of crotalphine (3.8ngkg-1) did not cause important clinical or behavioral changes and promotes antinociceptive effect on incised ischial region for seven days in horses. Moreover, crotalphine did not evoke relevant anti nociceptive effect on the scapular region or in intact skin of horses.

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