Chemical constituents, anti-inflammatory and analgesic activities of iridoids preparation from Phlomoides labiosa bunge.

This study reports the isolation of iridoids and cycloartane glycosides from the aerial parts of Phlomoides labiosa Bunge. Six compounds were isolated and the chemical structures were identified as phlorigidoside С (1), 8-O-acetylharpagide (2), shanzhiside methyl ester (3), cyclosiversioside A (4), cyclosiversioside E (5), and cyclosiversioside C (6). Compounds 4-6 are reported for the first time in this plant. In addition, anti-inflammatory and analgesic activities of iridoid fraction were studied. The sum of iridoids (SI) with intragastric administration is 5.2 and 52.5 times less toxic, than such market drugs as analgin and diclofenac sodium, respectively. In terms of the latitude of analgesic action (LD50/ED50), the SI exceeds analgin by 19.2 times and diclofenac sodium by 16 times. The anti-inflammatory and analgesic activities of the sum of iridoids were confirmed to be effective and nontoxic, and exceed known drugs diclofenac sodium and analgin (metamizole sodium).

Oxidative damage of canine erythrocytes after treatment with non-steroidal anti-inflammatory drugs.

OBJECTIVE: To investigate oxidative erythrocyte damage in dogs treated with different non-steroidal anti-inflammatory drugs. MATERIAL AND METHODS: Case-controlled prospective observational study using blood obtained from dogs presenting for lameness examinations or standard surgical procedures to a private referral clinic. Sampling was performed from April 2018 to July 2019. Groups comprised dogs receiving either metamizole (dipyrone) (22 dogs), carprofen (20 dogs) or meloxicam (20 dogs) for a minimum of 10 days. Dogs with gastrointestinal hemorrhage were excluded from the study. A complete hematological, as well as a basic biochemical profile were performed in every dog. Pappenheim stained blood smears were evaluated for eccentrocytes and brilliant cresyl blue stained smears for Heinz bodies. EDTA blood was frozen at -80°C immediately after sampling for measurement of superoxide dismutase and gluthathione peroxidase activity at an external laboratory. Hemoglobin concentration, superoxide dismutase and gluthathione peroxidase activities, reticulocyte count, eccentrocyte and Heinz body numbers were determined prospectively as key parameters for further statistical assessment with Kruskal-Wallis test and Dunn's multiple comparisons test. RESULTS: Dogs receiving metamizole showed a significant increase in eccentrocyte (median 14.5/500 cells vs. 0/500 cells in the other groups, p < 0.0001) and reticulocyte number (median 191.4 × 109/l vs. 31.6-37.9 × 109/l, p < 0.0001) and a significant decrease in hemoglobin concentration (median 8.4 mmol/l vs. 10.1-10.5 mmol/l, p < 0.0003). No significant difference in superoxide dismutase and gluthathione peroxidase activities was observed between dogs receiving metamizole and the other groups. Heinz bodies were not found in any of the dogs. CONCLUSION: Treatment with metamizole for 10 or more days resulted in decreased hemoglobin concentration, eccentrocytosis and reticulocytosis in dogs in this study. This might be a sign of increased oxidative damage caused by this drug. CLINICAL SIGNIFICANCE: Prolonged metamizole therapy should be evaluated critically in patients already affected by severe illness or underlying anaemia.

Assessment of the cytoprotective effect of the homeopathic compound Canova® on African green monkey kidney (VERO) cell line exposed to the drug dipyrone sodium.

Dipyrone or metamizole is one of the most frequently used analgesic worldwide. Despite its widespread use, this drug may exert genotoxic and cytotoxic effects on lymphocytes. Therefore, studies with therapeutic agents that may provide protection against these effects are important. The homeopathic compound Canova® (CA) appears to be a beneficial candidate for preventing DNA damage and cellular lethality, since this compound acts as an immunomodulator associated with cytoprotective actions. Hence, the aim of the present investigation was to determine the potential cytoprotective effects of CA using cell line VERO as a model. VERO cells were incubated with sodium dipyrone and subsequently subject to the comet, apoptosis and immunocytochemistry assays. Data demonstrated that sodium dipyrone induced an increase in DNA damage index (DI) employing the comet assay. However, when VERO cells were co-treated with CA at the three concentrations studied, a significant reduction in DI was observed, indicating an antigenotoxic effect attributed to CA. Further dipyrone induced an elevation in %apoptosis at 24 and 48 hr. However, when dipyrone was co-incubated with CA, a significant reduction in %apoptosis was noted at the three concentrations of CA employed. Results from immunocytochemical analysis showed a rise in the expression of caspase 8 and cytochrome C when cells were exposed to dipyrone. In contrast, co-treatment of dipyrone and CA significantly reduced the effect of dipyrone. Therefore, evidence indicated that CA acted as an anticytotoxic and antigenotoxic agent counteracting damage induced by dipyrone.

Magnetic microspheres based on pectin coated by chitosan towards smart drug release.

This study reports the preparation of microspheres of pectin and magnetite nanoparticles coated by chitosan to encapsulate and deliver drugs. Magnetic-pectin microspheres were obtained by ionotropic gelation followed by polyelectrolyte complexation with chitosan. Characterization data show that magnetite changes the physicochemical and morphological properties of the microspheres compared to the non-magnetic samples. Using metamizole (Mtz) as a drug model, the magnetic microspheres showed appreciable encapsulation efficiency (85 %). Release experiments performed in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids suggested that the release process is pH-dependent. At pH 6.8, the Mtz release is favored achieving 75 % after 12 h. The application of an external magnetic field increased the release to 91 % at pH 6.8, indicating that the release also is magnetic-dependent. The results suggest that the magnetic microspheres based on pectin/chitosan biopolymers show the potential to be used as a multi-responsive drug delivery system.

Role of ß-Caryophyllene in the Antinociceptive and Anti-Inflammatory Effects of Tagetes lucida Cav. Essential Oil.

Tagetes lucida Cav. (Asteraceae) is an ancient medicinal plant commonly used to alleviate pain. Nevertheless, scientific studies validating this property are lacking in the literature. Animal models of pain were used to evaluate the antinociceptive and anti-inflammatory activities of T. lucida essential oil (TLEO) and a bioactive metabolite. The chemical constitution and possible toxicity of the extract and the mechanism of action of ß-caryophyllene were also explored. Temporal course curves and dose-response graphics were generated using TLEO (0.1-10 mg/kg or 3.16-31.62 mg/kg) and ß-caryophyllene (3.16-10 mg/kg). Metamizole (80 mg/kg) and indomethacin (20 mg/kg) were used as reference drugs in the formalin assay and writhing test in rats and mice, respectively. The ß-caryophyllene mechanism of action was explored in the presence of naloxone (1 mg/kg), flumazenil (10 mg/kg), WAY100635 (0.16 mg/kg), or nitro-l-arginine methyl ester (L-NAME) (20 mg/kg) in the formalin test in rats. GC/MS analysis demonstrated the presence of geranyl acetate (49.89%), geraniol (7.92%), and ß-caryophyllene (6.27%). Significant and dose-dependent antinociceptive response was produced by TLEO and ß-caryophyllene without the presence of gastric damage. In conclusion, ß-caryophyllene was confirmed as a bioactive compound in the T. lucida analgesic properties by involving the participation of receptors like opioids, benzodiazepines, and Serotonin 1A receptor (5-HT1A), as well as nitric oxide.

Metamizole for Postoperative Pain in Pediatric Patients Undergoing Subarachnoid Anesthesia.

BACKGROUND: Efficient postoperative pain management, which is aimed at decreasing the risk of complications and drug-induced side effects, without affecting the quality of analgesia, is part of today's concept of enhanced recovery after surgery, that is, fast-track surgery. STUDY QUESTION: The objective of this study was to determine whether effective management of acute postoperative pain was possible without opioids, while avoiding complications, drug-induced side effects, and suboptimal treatment. Introduction of metamizole, which has regained popularity, into a multimodal analgesia regimen was used, as opioids are not routinely administered. STUDY DESIGN: The study was prospective, observational, unrandomized, and without the control group. MEASURES AND OUTCOMES: This study was performed in a pediatric hospital with 300 beds and an average of 1700 annual surgical interventions. The study group comprised 378 patients aged 1-17 years, undergoing lower abdominal or limb surgery between June 2016 and June 2017. Children underwent subarachnoid anesthesia combined with intravenous sedation and received not routinely but on demand postoperative opioid analgesia. The pain was self-assessed by the pediatric patient or was assessed by the nurse using pain scores. RESULTS: Metamizole proved to be safe, efficient, and very well tolerated by children. Multimodal analgesia using acetaminophen, nonsteroidal anti-inflammatory drug with metamizole for the treatment of moderate to severe pain in children undergoing surgery, required a single opioid dose in 292 patients (77.24%) of the 378 in this study. CONCLUSIONS: In pediatric patients undergoing surgery, subarachnoid anesthesia combined with intravenous sedation, multimodal analgesia that includes metamizole, and nonpharmacological complementary therapies in pain management enable avoidance or reduction of opioids to a single dose, without undertreatment. There is also a minimum of anesthesia, accelerated children's recovery and a rapid return to presurgical levels of function.

Comparative Analgesia Between Acupuncture and Dipyrone in Odontalgia.

The aim of this study was to assess whether the effectiveness of acupuncture is similar to the use of analgesics in the management of toothache. The research included 56 volunteers who were divided into 4 groups: Real Acupuncture group, Placebo Acupuncture group, Real Dipyrone group, and Placebo Dipyrone group. The interventions of the study were performed before the dental care. Inclusion criteria were toothache of pulpal origin with pain scale (Visual Analogue Scale) above 4, absence of medication for the pain, and aged over 18 years. The Real Acupuncture volunteers received a session of acupuncture using piercing needles, while volunteers from the Placebo Acupuncture group received an acupuncture session using non-piercing sham needles. Volunteers from the Real Dipyrone group received a dipyrone tablet and the Placebo Acupuncture group received a tablet with no active ingredient. Before any therapeutic intervention, we collected samples from the volunteers' saliva to analyze the salivary cortisol, the volunteers rated the intensity of their pain using VAS, and we measured their energy level by the Ryodoraku method. After 20 minutes of treatment, all the volunteers' analysis parameters were collected again. The Real Acupuncture group presented a greater reduction of VAS than the reduction obtained by the Real Dipyrone group (p<0.05). There was no statistically significant difference between the groups for the salivary cortisol and energy level variables. It can be concluded that acupuncture was more effective in reducing odontalgia than the dipyrone and that it can be an alternative for odontalgia management.

Treating Therapy-Resistant Headache After Aneurysmal Subarachnoid Hemorrhage with Acupuncture.

INTRODUCTION: Subarachnoid haemorrhage (SAH) is usually associated with severe headache, whereas the options of pharmacological analgesia are restricted. Acupuncture is a promising method in treatment of headaches associated with meningeal sensitivity or irritation, such as migraine or post-dural puncture headache. CASE REPORT: We report on 3 patients, who suffered severe headache due to aneurysmal SAH, and received acupuncture when pharmacological measures were exhausted. After acupuncture treatment all patients reported at least 50% pain reduction and could stop or reduce analgesics without side effects. DISCUSSION: Acupuncture may be an effective pain treatment method in patients suffering from headache due to SAH. Randomized trials using acupuncture as an add-on to standard analgesic therapy would help evaluate the role of acupuncture for this purpose.

Broccoli sprouts produce abdominal antinociception but not spasmolytic effects like its bioactive metabolite sulforaphane.

Abdominal pain is a common health problem that requires efficacious and safe therapy. Broccoli is a rich source of health-promoting bioactive compounds with potential for pain therapy. However, there is a lack of scientific pharmacological evidence to support this. Our aim was to investigate the antinociceptive and spasmolytic activities of broccoli aqueous extracts from seeds, sprouts, and inflorescence, as well as some metabolites. Experiments were done using enteral and parenteral administration in an in vivo model of pain accompanied with an in vitro assay. Data established that sprouts (100 mg/kg, i.p. and 1000 mg/kg, p.o.) produced significant and major antinociceptive effect at similar or even lower doses in comparison to the seeds (125 mg/kg, i.p. and 1000 mg/kg, p.o.) and broccoli heads (250 mg/kg, i.p. and 1000 mg/kg, p.o.). These results resembled the analgesic response observed with the reference drug metamizole (80 mg/kg, i.p.). Chlorogenic acid (CA, 3, 10, 30, and 100 mg/kg, i.p.) and SFN (0.1, 1 and 10 mg/kg, i.p.) were partial responsible antinociceptive metabolites of broccoli. SFN effects involved participation of endogenous opioids, since they were inhibited in the presence of naltrexone (5 mg/kg, s.c.). In the in vitro assay, a significant 80% spasmolytic-like response was reached with SFN alone in comparison to 20% obtained with aqueous extracts of sprouts and seeds. Participation of calcium channels was a mechanism involved in the in vitro response of SFN. In conclusion, broccoli sprouts, SFN and CA are potential nutraceuticals for abdominal pain therapy.

Chitosan/waste coffee-grounds composite: An efficient and eco-friendly adsorbent for removal of pharmaceutical contaminants from water.

Waste coffee-grounds (WCG), a poorly explored source of biocompounds, were combined with chitosan (Cs) and poly(vinyl alcohol) (PVA) in order to obtain composites. Overall, WCG showed a good interaction with the polymeric matrix and good dispersibility up to 10 wt-%. At 5 wt-% WCG, the composite exhibited a noticeable enhancement (from 10 to 44%) of the adsorption of pharmaceuticals (metamizol (MET), acetylsalicylic acid (ASA), acetaminophen (ACE), and caffeine (CAF)) as compared to the pristine sample. The highest removal efficiency was registered at pH 6 and the removal followed the order ASA > CAF > ACE > MET. For all pharmaceuticals, the adsorption kinetics was found to follow the pseudo-second order model, while the adsorption mechanism was explained by the Freundlich isotherm. Reuse experiments indicated that the WCG-containing composite has an attractive cost-effectiveness since it presented a remarkable reusability in at least five consecutive adsorption/desorption cycles.

Aspirin for acute treatment of episodic tension-type headache in adults.

BACKGROUND: Tension-type headache (TTH) affects about 1 person in 5 worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (two to 14 headache days per month), and chronic TTH (15 headache days per month or more). Aspirin is one of a number of analgesics suggested for acute treatment of episodic TTH. OBJECTIVES: To assess the efficacy and safety of aspirin for acute treatment of episodic tension-type headache (TTH) in adults compared with placebo or any active comparator. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and the Oxford Pain Relief Database from inception to September 2016, and also reference lists of relevant published studies and reviews. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers' websites. SELECTION CRITERIA: We included randomised, double-blind, placebo-controlled studies (parallel-group or cross-over) using oral aspirin for symptomatic relief of an acute episode of TTH. Studies had to be prospective, with participants aged 18 years or over, and include at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and extracted data. For various outcomes (predominantly those recommended by the International Headache Society (IHS)), we calculated the risk ratio (RR) and number needed to treat for one additional beneficial outcome (NNT), one additional harmful outcome (NNH), or to prevent one event (NNTp) for oral aspirin compared to placebo or an active intervention.We assessed the evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS: We included five studies enrolling adults with frequent episodic TTH; 1812 participants took medication, of which 767 were included in comparisons of aspirin 1000 mg with placebo, and 405 in comparisons of aspirin 500 mg or 650 mg with placebo. Not all of these participants provided data for outcomes of interest in this review. Four studies specified using IHS diagnostic criteria; one predated commonly recognised criteria, but described comparable characteristics and excluded migraine. All participants treated headaches of at least moderate pain intensity.None of the included studies were at low risk of bias across all domains considered, although for most studies and domains this was likely to be due to inadequate reporting rather than poor methods. We judged one study to be at high risk of bias due to small size.There were no data for aspirin at any dose for the IHS preferred outcome of being pain free at two hours, or for being pain free at any other time, and only one study provided data equivalent to having no or mild pain at two hours (very low quality evidence). Use of rescue medication was lower with aspirin 1000 mg than with placebo (2 studies, 397 participants); 14% of participants used rescue medication with aspirin 1000 mg compared with 31% with placebo (NNTp 6.0, 95% confidence interval (CI) 4.1 to 12) (low quality evidence). Two studies (397 participants) reported a Patient Global Evaluation at the end of the study; we combined the top two categories for both studies to determine the number of participants who were 'satisfied' with treatment. Aspirin 1000 mg produced more satisfied participants (55%) than did placebo (37%) (NNT 5.7, 95% CI 3.7 to 12) (very low quality evidence).Adverse events were not different between aspirin 1000 mg and placebo (RR 1.1, 95% CI 0.8 to 1.5), or aspirin 500 mg or 650 mg and placebo (RR 1.3, 95% CI 0.8 to 2.0) (low quality evidence). Studies reported no serious adverse events.The quality of the evidence using GRADE comparing aspirin doses between 500 mg and 1000 mg with placebo was low or very low. Evidence was downgraded because of the small number of studies and events, and because the most important measures of efficacy were not reported.There were insufficient data to compare aspirin with any active comparator (paracetamol alone, paracetamol plus codeine, peppermint oil, or metamizole) at any of the doses tested. AUTHORS' CONCLUSIONS: A single dose of aspirin between 500 mg and 1000 mg provided some benefit in terms of less frequent use of rescue medication and more participants satisfied with treatment compared with placebo in adults with frequent episodic TTH who have an acute headache of moderate or severe intensity. There was no difference between a single dose of aspirin and placebo for the number of people experiencing adverse events. The amount and quality of the evidence was very limited and should be interpreted with caution.

Antinociceptive effect of systemically administered dipyrone (metamizol), magnesium chloride or both in a murine model of cancer.

BACKGROUND: Opioid effectiveness to treat cancer pain is often compromised by the development of tolerance and the occurrence of undesirable side effects, particularly during long-term treatment. Hence, the search for more efficient analgesics remains a necessity. The main goal of this study was to relieve neuropathic symptoms associated with tumour growth by administering the non-opioid analgesic dipyrone (DIP) alone or in combination with magnesium chloride (MgCl2 ), an adjuvant that blocks the NMDA receptor channel. METHODS: Mice were inoculated with a melanoma cell line (B16-BL6) in the left thigh and two protocols were used to evaluate the effect of DIP (270 mg/kg), MgCl2 (200 mg/kg), or the combination DIP-MgCl2 . In the therapeutic protocol the drugs, alone or combined, were administered once tumour had promoted increased nociception. In the preventive protocol, drugs were administered prior to the appearance of the primary tumour. Tumour growth was assessed with a caliper and nociception was determined using behavioural tests. RESULTS: DIP promoted antinociception only at the beginning of both protocols due to the development of tolerance. The combination DIP-MgCl2 improved the antinociceptive effect, avoiding tolerance and reducing tumour growth in the preventive treatment, more efficiently than each compound alone. CONCLUSIONS: These results suggest that DIP-MgCl2 may represent a safe, affordable and accessible option to reduce tumour growth and to treat cancer pain avoiding the risk of tolerance, without the typical complications of opioids agents, particularly when long-term treatment is required. SIGNIFICANCE: This study shows a non-opioid analgesic combined with an adjuvant as a therapeutic option to treat cancer pain. The avoidance of antinociceptive tolerance when repeated administration is required, as well as tumor growth reduction, are additional advantages to be considered.

Prospective randomized controlled trial comparing standard analgesia with combined intra-operative cystic plate and port-site local anesthesia for post-operative pain management in elective laparoscopic cholecystectomy.

BACKGROUND: Various mechanisms, including somatic and visceral nociceptive stimulation, have been suggested as a cause for pain after laparoscopic cholecystectomy (LC). We therefore conducted a prospective randomized controlled trial (PRCT) to evaluate whether somatovisceral pain blockade reduces pain after LC. HYPOTHESIS: Analgesic efficacy of multimodal analgesia is superior to standard analgesia for patients undergoing elective LC for symptomatic cholelithiasis. Specifically, topical cystic plate and port-site injection with 0.25 % bupivacaine significantly reduces pain after LC. DESIGN: This study was designed as single-blinded PRCT. SETTING: This study was conducted in an academic medical center. PATIENTS AND METHODS: Between February and May 2010 we randomly assigned 63 patients with symptomatic cholelithiasis in a 1:1 ratio to non-opioid/opioid analgesic combinations (Control Group, n = 32) and non-opioid/opioid analgesic combinations plus topical 0.25 % bupivacaine onto the cystic plate and local 0.25 % bupivacaine port-site injection, post-LC (Study Group, n = 31). Primary endpoint was patient-reported pain 1, 4, 6, 12, 24 h and 1 week post-LC using the Visual Analog Scale (VAS 0-10). RESULTS: Study groups were comparable clinicopathologically. There were no adverse events. A statistically significant reduction in mean pain score was apparent in Study Group patients in comparison with Control Group (mean VAS 4.83 ± 2.33 vs. 6.80 ± 1.87; p < 0.001) at all early (1-6 h) post-operative time points following LC. CONCLUSION: This PRCT shows significantly improved pain control with somatovisceral pain blockade over non-opioid/opioid analgesic combinations following LC for symptomatic cholelithiasis. For centers not utilizing adjunctive local anesthetic for LC, this topical use of bupivacaine may improve patient comfort during recovery. This trial was registered on www.ClinicalTrials.gov NCT# 01972620.

Metamizol Relieves Pain Without Interfering With Cerulein-Induced Acute Pancreatitis in Mice.

OBJECTIVES: Animal models are essential to understand the pathogenesis of acute pancreatitis (AP) and to develop new therapeutic strategies. Although it has been shown that cerulein-induced AP is associated with pain in experimental animals, most experiments are carried out without any pain-relieving treatment because researchers are apprehensive of an interference of the analgetic agent with AP-associated inflammation. In light of the growing ethical concerns and the legal tightening regarding animal welfare during experiments, this attitude should be changed. METHODS: Acute pancreatitis was induced by cerulein in the C57BL/6J and FVB/N mouse inbred strains. One group received vehicle only, and the other was treated with metamizol as analgetic agent. Pain sensation and parameters of AP were analyzed as well as the effect of metamizol in the pancreas and its actions in the brain. RESULTS: We report that oral administration of metamizol protects cerulein-treated mice from abdominal pain without influencing the clinical and histopathological course of the disease. In addition, it could be shown that metamizol reduces the central pain response. CONCLUSIONS: This study reveals that oral administered metamizol has no influence on the cerulein-induced AP and can be given as an analgesic to increase animal welfare in experiments with induced AP.

Pain management during radiotherapy and radiochemotherapy in oropharyngeal cancer patients: single-institution experience.

AIM OF THE STUDY: Radiotherapy (RT) is a radical therapeutic option for patients with oropharyngeal cancer (OPC). It induces an acute postradiation reaction that may cause significant pain. The aim of this study was to analyse pain occurrence and intensity, as well as type and effectiveness of analgesic treatment, in OPC patients undergoing RT or radiochemotherapy (RT-CT). MATERIAL AND METHODS: Retrospective data were obtained for 42 OPC patients at clinical stages I-IVA, treated with adjuvant RT or RT-CT or definite RT or RT-CcT at the Comprehensive Cancer Center in Bialystok, Poland. Pain intensity and type of analgesic treatment during the therapy were analysed and compared with the intensity of the radiation-induced acute reaction, assessed weekly according to the Dische score. RESULTS: Thirty-nine (92.9%) patients received analgesic treatment. Analgesic therapy was started in 27 (64.3%) patients with administration of non-steroidal anti-inflammatory drugs (NSAIDs) and/or paracetamol, in seven (16.7%) with mild opioids and in five (11.9%) with strong opioids. Strong opioids were used during therapy in 21 (50%) patients. Co-analgesics were administered to six patients. Breakthrough pain was observed in 10 (23.8%) patients. CONCLUSIONS: High incidence of pain during RT and RT-CT calls for increased awareness of the importance of pain monitoring and treatment during RT of OPC patients. The analgesic treatment had to be adjusted individually.

A Comparative Investigation of the Analgesic Effects of Metamizole and Paracetamol in Rats.

BACKGROUND: This study investigated the effects of metamizole and paracetamol on pain and oxidative stress induced by scalpel incision and carrageenan in rats. MATERIALS AND METHODS: Total of 144 rats were divided into groups of 12 animals. Six groups each were used for scalpel incision and carrageenan tests. Pain was inflicted by applying a scalpel incision or carrageenan. Pain-created groups by scalpel incision received metamizole (SIM) or paracetamol (SIP) at doses of 250 or 500 mg/kg. Pain-created groups by carrageenan received metamizole (CAM) or paracetamol (CAP) at doses of 250 or 500 mg/kg. Analgesic activity was determined by Basile Algesimeter. The COX-2 and MPO gene expressions were determined, and malondialdehyde and tGSH were measured in rat paws. RESULTS: In the scalpel incision test, pain was reduced in groups of SIM-250 and SIM-500 in the first hour by 65.2% and 91.3%, respectively, and in the third hour by 51.9% and 77.8%, respectively, compared with the SIC group. In SIP-250 and SIP-500 groups, pain was reduced in the first hour by 43% and 74%, respectively, and by 33.4% and 59.3%, respectively, in the third hour compared with the SIC group. In the carrageenan test, in groups CAM-250 and CAM-500, pain was reduced in the first hour by 72.3% and 86.1%, respectively, and by 65.8% and 71.4%, respectively, in the third hour compared with the CCG group. In groups CAP-250 and CAP-500, pain was reduced in the first hour by 52.8% and 69.4%, respectively, and by 28.6% and 25.8%, respectively, in the third hour compared with the CCG group. Metamizole inhibited COX-2 gene expression at a dose of 500 mg/kg in the carrageenan test. At doses of 250 and 500 mg/kg, metamizole reduced COX-2 and MPO gene expressions and oxidative stress induced by scalpel incision or carrageenan. But both doses of paracetamol were unable to suppress that parameters. CONCLUSIONS: Our results show that metamizole is more effective than paracetamol for treating surgical trauma-related pain, inflammation, and oxidative stress and hence may be a preferential drug to paracetamol.

Arnica montana en el tratamiento del dolor después de la odontectomía de terceros molares retenidos / Arnica montana in the treatment of pain after the odontectomy of third retained molars

Se realizó un estudio de intervención terapéutica en 80 pacientes con dolor luego de la extracción de terceros molares retenidos, en el Hospital Provincial Docente Clinicoquirúrgico "José Ramón López Tabrane" de la provincia de Matanzas, desde enero del 2012 hasta igual mes del 2013, con vistas a evaluar la evolución de estos. Para ello se formaron 2 grupos de 40 integrantes cada uno; a uno se le indicó tratamiento convencional con dipirona de 300 mg (grupo de control) y al otro, homeopatía con Arnica montana en 30 ch (grupo experimental). Los resultados demostraron la existencia de una terapia alternativa que podría ser utilizada cuando los medicamentos de primera elección hayan fallado, ya sea por su baja eficacia o por la aparición de reacciones adversas. En los pacientes tratados con Arnica montana, el efecto fue satisfactorio; además, este remedio homeopático es seguro y menos costoso para el Sistema Nacional de Salud cubano.

A therapeutic intervention study was carried out in 80 patients with pain after the extraction of third retained molars, in "José Ramón López Tabrane" Teaching Provincial Clinical-Surgical Hospital in Matanzas province, from January, 2012 to the same month of 2013, with the objective of evaluating their clinical course. For this purpose, 2 groups of 40 members each were formed; conventional treatment with dipyrone of 300 mg (control group) was indicated to one of them, and to the other homeopathy with Arnica montana in 30 ch (experimental group). The results demonstrated the existence of an alternative therapy that could be used when first election drugs have failed, either for their low effectiveness or for the emergence of adverse reactions. In the patients treated with Arnica montana, the effect was satisfactory; also, it can be said that this homeopathic remedy is safe and less expensive for the Cuban National Health System.

Arnica montana en el tratamiento del dolor después de la odontectomía de terceros molares retenidos / Arnica montana in the treatment of pain after the odontectomy of third retained molars

Se realizó un estudio de intervención terapéutica en 80 pacientes con dolor luego de la extracción de terceros molares retenidos, en el Hospital Provincial Docente Clinicoquirúrgico José Ramón López Tabrane de la provincia de Matanzas, desde enero del 2012 hasta igual mes del 2013, con vistas a evaluar la evolución de estos. Para ello se formaron 2 grupos de 40 integrantes cada uno; a uno se le indicó tratamiento convencional con dipirona de 300 mg (grupo de control) y al otro, homeopatía con Arnica montana en 30 ch (grupo experimental). Los resultados demostraron la existencia de una terapia alternativa que podría ser utilizada cuando los medicamentos de primera elección hayan fallado, ya sea por su baja eficacia o por la aparición de reacciones adversas. En los pacientes tratados con Arnica montana, el efecto fue satisfactorio; además, este remedio homeopático es seguro y menos costoso para el Sistema Nacional de Salud cubano(AU)

A therapeutic intervention study was carried out in 80 patients with pain after the extraction of third retained molars, in José Ramón López Tabrane Teaching Provincial Clinical-Surgical Hospital in Matanzas province, from January, 2012 to the same month of 2013, with the objective of evaluating their clinical course. For this purpose, 2 groups of 40 members each were formed; conventional treatment with dipyrone of 300 mg (control group) was indicated to one of them, and to the other homeopathy with Arnica montana in 30 ch (experimental group). The results demonstrated the existence of an alternative therapy that could be used when first election drugs have failed, either for their low effectiveness or for the emergence of adverse reactions. In the patients treated with Arnica montana, the effect was satisfactory; also, it can be said that this homeopathic remedy is safe and less expensive for the Cuban National Health System(AU)

Analgesic activity of diterpene alkaloids from Aconitum baikalensis.

We compared analgesic activities of individual alkaloids extracted from Baikal aconite (Aconitum baikalensis): napelline, hypaconitine, songorine, mesaconitine, 12-epinapelline N-oxide. The detected analgesic activity was comparable to that of sodium metamizole. The mechanisms of analgesia were different in diterpene alkaloids of different structure. The antinociceptive effect of atisine alkaloids (12-epinapelline N-oxide, songorine) was naloxonedependent and realized via opioid receptor modulation.