Central Analgesic Effects Research Articles

L’intoxication au protoxyde d’azote : un nouveau défi pour la biologie médicale

AbstractNitrous oxide (N2O) is a gas used in medicine for its anesthetic and analgesic properties, and in industry as an oxidizing gas or propellant. This gas is also available on self-service for food use. In recent years, its use has been increasingly diverted to recreational purposes. Between 2020 and 2021, the number of serious cases of intoxication increased by 320% in France, demonstrating a major public health concern. It is also a problem for road safety, with an increase in the number of road accidents linked to the consumption of this gas. Nitrous oxide causes both short-term effects (euphoria, disorientation, etc.) and long-term effects (sensory and motor neurological disorders and thrombosis). This gas acts on the central nervous system, inducing anxiolytic, anesthetic, antidepressant and analgesic effects. Nitrous oxide is difficult to quantify because of its rapid elimination. Biological investigation is thus based on secondary anomalies linked to vitamin B12 inactivation: increased methylmalonic acid and homocysteine levels. However, these two biological markers are not specific to nitrous oxide intoxication. To improve patient support, we need to find new biological markers that are more specific to nitrous oxide intoxication.

A Biomimetic Nociceptor Based on a Vertical Multigate, Multichannel Neuromorphic Transistor.

Nociceptors, crucial sensory receptors within biological systems, are essential for survival in diverse and potentially hazardous environments. Efforts to replicate nociceptors through advanced electronic devices, such as memristors and neuromorphic transistors, have achieved limited success, capturing basic nociceptive functions while more advanced characteristics like various forms of central sensitization and analgesic effect remain out of reach. Here, we introduce a vertical multigate, multichannel electrolyte-gated transistor (Vm-EGT), designed to mimic nociceptors. Utilizing the hybrid mechanism combining electric-double-layer (EDL) with ion intercalation/deintercalation in EGTs, our approach successfully replicates peripheral sensitization and desensitization characteristics of nociceptors. The intricate multigate and multichannel design of the Vm-EGT enables the emulation of more advanced nociceptive functionalities, including central sensitization and analgesic effect. Furthermore, we demonstrate that by exploiting the inherent current-voltage relationship, the Vm-EGT can simulate these advanced nociceptive features and seamlessly transition between them. Integrating a Vm-EGT with a thermistor and a heating plate, we have developed an artificial thermal nociceptor that closely mirrors the sensory attributes of its biological counterpart. Our approach significantly advances the emulation of nociceptors, providing a basis for the development of sophisticated artificial sensory systems and intelligent robotics.

Phyto-pharmacological and computational profiling of Bombax ceiba Linn. Leaves revealed pharmacological properties against oxidation, hyperglycemia, pain, and diarrhea

The present study aimed to conduct phytochemical and pharmacological profiling of methanolic crude extract of leaves of Bombax ceiba Linn. via experimental and computational approaches. Six secondary metabolites were isolated chromatographically, and the structures were elucidated by extensive analyses of high-resolution 1H and 13C NMR data. The separated compounds were characterized as β-sitosterol (1), β-amyrin (2), β-amyrin acetate (3), β-amyrin palmitate (4), β-amyrone (5), and isoscopoletin (6). DPPH free radical scavenging assay, tail-tipping method, writhing assay, and castor oil-induced diarrheal mice methods, respectively, were used to assess the antioxidant, hypoglycemic, analgesic, and anti-diarrheal activities of the leaf extract of B. ceiba plant species. The study observed significant reductions (p < 0.05) in the level of blood glucose at 30, 60, 120, and 180 min following the administration of the crude extracts (200 mg/kg body weight (bw) and 400 mg/kg bw). These reductions occurred in a time-dependent manner. Additionally, both doses of the investigated extracts exhibited significant (p < 0.05) central and peripheral analgesic effects compared to morphine (2 mg/kg bw) and diclofenac sodium (50 mg/kg bw), respectively. Furthermore, the 400 mg/kg bw extract demonstrated anti-diarrheal activity, reducing 54.17 % of diarrheal episodes in mice compared to loperamide with 70.83 % inhibition. The computational investigations yielded results consistent with existing in vivo findings. The results obtained from molecular docking showed that the isolated compounds had a better or comparable binding affinity to the active binding sites of the glutathione reductase enzyme, mu-opioid receptor, cyclooxygenase 2 (COX-2), glucose transporter 3 (GLUT 3), and kappa opioid receptor. These findings may indicate that the compounds isolated from the B. ceiba plant species have antioxidant, analgesic, hypoglycemic, and anti-diarrheal, properties. Consequently, it was inferred that the plant B. ceiba might be beneficial in dealing with oxidation, diarrhea, hyperglycemia, and pain. Nonetheless, further investigations are necessary to perform thorough phytochemical profiling and elucidate the exact mechanistic ways of the crude extract and the isolated phytoconstituents.

EARLY ACTIVATION PATHWAYS IN PATIENTS UNDERGOING OPEN HEART SURGERY WITH MULTICOMPONENT GENERAL ANESTHESIA COMBINED WITH HIGH THORACIC EPIDURAL ANESTHESIA

Background: Early mobilization of patients in the postoperative period after open heart surgeries, significantly decreases the risk of complications, accelerates the restoration of functional capacity, shortens the length of hospital stay, and reduces treatment costs Materials and methods: Open heart surgeries were performed on 60 patients at Ankara "Bayındır" Hospital, Central Clinical Hospital, and Baku Health Center were included in the study. Patients were divided into two groups. 30 of them underwent the procedure with the use of multi-component balanced general anesthesia and intravenous fentanyl analgesia in the postoperative period. The other group of 30 patients underwent catheterization under high thoracic epidural anesthesia, with the administration of ropivacaine prior to induction and, in the postoperative period, ropivacaine and fentanyl. We conducted a study on central hemodynamic parameters and analgesic effects. Results: Thirty of them underwent the procedure with the use of multi-component general anesthesia and intravenous fentanyl analgesia in the postoperative period. The other group of 30 patients underwent catheterization of the high epidural space with the administration of ropivacaine before induction and, in the postoperative period, ropivacaine and fentanyl. We conducted a study on central hemodynamic parameters and analgesic effects. Conclusion: It has been established that for patients in the second group according to the Enhanced Recovery After Surgery strategy, hemodynamic support and effective pain management can contribute to early patient mobilization after surgery. Early mobilization, in turn, can expedite recovery and reduce the length of hospital stay, ultimately leading to potential cost savings.

Isolation, Chemical Modification and In vivo Pharmacological Screening of Piperine and its Derivatives

Piperine (1) extracted from black pepper was transformed into its derivatives piperic acid (2) and piperonal (3) with good yields (69-76%). Animal models were used to examine the compounds' in vivo peripheral as well as central analgesic and anti-inflammatory effects. In the peripheral analgesic experiment, compound 2 displayed remarkable action having writhing inhibition by 78% at 50 mg/kg dose, superior to that of 1 (74% writhing inhibition) when administered at the same dose and compared with standard diclofenac sodium (85%). Concerning central analgesic efficacy, piperonal outperformed compounds 1 and 2 at 25 mg/kg dose, with % tail-flick elongation times of 194%, 178%, and 178% at 30, 60, and 90 min, respectively. Conversely, at 50 mg/kg dose, piperic acid exhibited the highest activity, demonstrating % tail-flick elongation times of 231%, 213%, and 206% at 30, 60, and 90 min, respectively, as compared to the standard morphine (278%, 247%, and 160%) in the same duration. In anti-inflammatory property evaluation, piperonal portrayed outstanding effects with paw edema inhibitions of 57%, 66%, 76%, and 81%, respectively from 1st hour onwards, compared to standard aceclofenac (61%, 72%, 78%, and 89%) and parent compound piperine (20%, 34%, 51%, and 60%). This study suggests that piperine derivatives could act as promising leads for future drug development. Dhaka Univ. J. Pharm. Sci. 23(1): 13-22, 2024 (June)

Analgesic effects of semi-solid extract from four medicinal herbs (Clinacanthus nutans (Burm. f.) Lindau, Vitex negundo L., Justicia gendarussa L., Piper lolot L.) in mice

Objectives: This study was conducted with the aim of evaluating the experimental analgesic effects of the semi-solid extract from four folk medicinal herbs: Clinacanthus nutans (Burm. f.) Lindau, Vitex negundoL., Justicia gendarussa L., and Piper lolot L. (BNTL extract). This study provides a scientific basis for further research on the effects of a topically applied natural-origin remedy. Materials and methods: Swiss albino mice, 20±2 g in weight, provided by the Pasteur Institute in Ho Chi Minh city. Hot-plate method and mechanical pain method were used to determine the analgesic effects of BNTL extract. Results: BNTL extract applied topically showed only a statistically significant effect on prolonging the response time compared with the control group to mechanical agents. BNTL extract helps prolong the time to appear temperature response in white mice, but has no statistical significance compared to the control group in the hot plate model. Conclusions: BNTL extract did not show central analgesic effects, but did show analgesic effects in experimental mechanical pain models.

Tegileridine: First Approval.

Tegileridine () is a small molecule μ-opioid receptor biased agonist developed by Jiangsu Hengrui Pharmaceuticals Co., Ltd for the treatment of postoperative pain. Tegileridine selectively activates the G-protein-coupled pathway, which mediates strong central analgesic effects and only weakly activates the β-arrestin-2 pathway implicated in adverse events like respiratory depression and gastrointestinal dysfunction. In January 2024, tegileridine received its first approval in China for the treatment of moderate to severe pain after abdominal surgery. This article summarizes the milestones in the development of tegileridine leading to this first approval for the treatment of moderate to severe pain after abdominal surgery.

Exploring the phytochemical, antioxidant, antimicrobial and analgesic potentials of Solanum erianthum as an alternative biological feedstock for producing sustainable biochemicals

Solanum erianthum is a medicinal herb that offers health benefits and valuable phytochemicals in treating human ailments. Phytochemicals and therapeutic properties of different parts of S. erianthum in four solvents: water, petroleum ether, chloroform, and methanol were evaluated. Stem showed high alkaloids (15.40 ± 0.7%) and tannins (8.6 ± 0.3%), followed by higher root saponins (12.2 ± 0.2%). In contrast, leaf exhibited high flavonoid (13.5 ± 0.5%) and phenolic (12.30 ± 1.0%) contents. The petroleum ether extract of the stem had the highest 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging activity (70.66 ± 0.3%) and ferric reducing antioxidant power (FRAP) activity (70.55 ± 0.08 μg/mL). In contrast, the petroleum ether extract of the root had maximum total antioxidant capacity (TAC) (1.065 ± 0.6 absorbance at 695 nm), while the fruit aqueous extract showed highest activity in ferric thiocyanate assay (FTC) (61.53 ± 0.1). Antibacterial activity ranged from 19 to 51 mm, while antifungal was from 11 to 43 mm. The methanol extracts of the root and leaf showed the highest antimicrobial activity against the tested bacteria and fungi. The methanol extract of fruit showed the highest analgesic activity (11.98 ± 2.14 s) and writhing inhibition (1st phase 85.1% and 2nd phase 96.7%), as confirmed by the formalin-induced paw licking test. Fruit extract showed active central and peripheral analgesic effects in early (88.9%) and late (92.8%) phases of pain, comparable to paracetamol (60 mg/kg). In conclusion, this study demonstrates the antioxidant, antimicrobial, and antifungal properties as well as central and peripheral analgesic effects of S. erianthum extracts.

Cellular and molecular mechanisms involved in the analgesic effects of botulinum neurotoxin: A literature review.

Botulinum neurotoxins (BoNTs), derived from Clostridium botulinum, have been employed to treat a range of central and peripheral neurological disease. Some studies indicate that BoNT may be beneficial for pain conditions as well. It has been hypothesized that BoNTs may exert their analgesic effects by preventing the release of pain-related neurotransmitters and neuroinflammatory agents from sensory nerve endings, suppressing glial activation, and inhibiting the transmission of pain-related receptors to the neuronal cell membrane. In addition, there is evidence to suggest that the central analgesic effects of BoNTs are mediated through their retrograde axonal transport. The purpose of this review is to summarize the experimental evidence of the analgesic functions of BoNTs and discuss the cellular and molecular mechanisms by which they can act on pain conditions. Most of the studies reviewed in this article were conducted using BoNT/A. The PubMed database was searched from 1995 to December 2022 to identify relevant literature.

ANALGESIC EFFECT OF “DINH THONG PHONG” CAPSULES ON EXPERIMENTAL ANIMALS

Purpose: Evaluate the analgesic effect of “Dinh Thong Phong” capsules on experimental animals. Subjects and Methods: “Dinh Thong Phong” capsules, meeting the standard criteria, were evaluated for analgesic effect on white mice. In particular, the central analgesic effect was assessed using the hot plate model, peripheral analgesic effect was assessed using the writhing pain model. Results: In the hot plate model, “Dinh Thong Phong” capsules at a dosage of 860 mg/kg and 2,580 mg/kg significantly increased the reaction time to heat (p &lt; 0.001) compared to the control group. The difference in reaction time to heat between the groups using “Dinh Thong Phong” capsules and the group using codeine phosphate at a dose of 20 mg/kg was not statistically significant (p &gt; 0.05). In the writhing model, “Dinh Thong Phong” capsules at a dose of 860 mg/kg and 2,580 mg/kg significantly reduced the number of writhing episodes (p &lt; 0.001) compared to the control group. The difference in the number of writhing episodes between the groups using “Dinh Thong Phong” capsules and the group using aspirin at a dose of 150 mg/kg was not statistically significant (p &gt; 0.05).

Various of Chemical and Pharmacological Applications of 1,3,4-Thiadiazole and It’s Derivative

1,3,4-Thiadiazole is a heterocyclic compound that has been widely studied for its diverse pharmacological activities. The compound is synthesized using different methods, including cyclization of linear organic derivative. The compound has been shown to exhibit various bioactivity, including its property as anticancer toward human cancers, antibacterial, diuretic, antitubercular, antifungal, and leishmanicidal agents, additionally, 1,3,4-thiadiazole derivatives have been shown to influence the central nervous system, displaying anti-inflammatory, anticonvulsant, analgesic, anxiolytic and antidepressant effects. 1,3,4-thiadiazole and its derivatives have been a subject of extensive research in the field of medicinal chemistry. These compounds exhibit a wide range of pharmacological activities, making them valuable candidates for drug development. The structural versatility of 1,3,4-thiadiazole derivatives allows for the fine-tuning of their pharmacological effects. The 1,3,4-thiadiazole moiety in a molecule enhances its bioactivity. Medicinal chemists have explored the SAR (Structure-Activity Relationship) of these derivatives to understand how different substitutions and modifications impact their pharmacological profiles. Synthesis and pharmacological activities of 1,3,4-thiadiazole and also its derivatives represent a vibrant area of research with promising implications for the progress of new therapeutic agents across various medical domains.

Central and Peripheral Analgesic and Anti-inflammatory effect of Plumbagin and Resveratrol: A Preclinical Study

Central and Peripheral Analgesic and Anti-inflammatory effect of Plumbagin and Resveratrol: A Preclinical Study

Study analgesic effects of basil extracts (Ocimum basilicum L.) on mice

Objectives: To study analgesic effects of basil extracts (Ocimum basilicum L.) on mice. Subjects and methods: The experiments were conducted according to heat stimulation (hot plate) and needle slide methods. In each experiment, mice were divided into 4 groups of 10 each, in which the negative control group was given distilled water, the positive one took the control drug, and the others were treated with basil extracts at the doses of 2.4 and 7.2 g/kg/day for 7 consecutive days. Mice in the control groups were drunk codeine phosphate 20 mg/kg or aspirin at a dose of 150 mg/kg depending on being in the hot plate or the needle pricking methods, respectively. The research indicators including response time to heat, pain force and pain response time of an individual mouse before and after drug administration were recorded. This study was conducted between October and November 2021 at Hanoi Medical University, Vietnam. Results: At oral doses of 2.4 and 7.2 g/kg/day x 7 days, basil extract showed better central analgesic effects in the treated groups than that in the control group (p &lt; 0.001), but these pain relief levels were lower than that of codeine phosphate at a dose of 20 mg/kg/day (p &lt; 0.001). In addition, basil extract had better effects on peripheral analgesia in the treated group than that in the control group (p &lt; 0.05 and p &lt; 0.01) and these effects were equivalent to those of aspirin at a dose of 150 mg/kg/day. Conclusions: The aqueous extract of basil has both central and peripheral analgesic effects in white mice at the dose regimens of 2.4 and 7.2 g/kg/day×7 consecutive days.

Mechanistic action of linalyl acetate: Acyclic monoterpene isolated from bitter orange leaf as anti-inflammatory, analgesic, antipyretic agent: Role of TNF-α, IL1β, PGE2, and COX-2

The intervention of inflammation disorders with conventional synthetic drugs has several hazards. Medicinal plants and their byproducts are beneficial in the treatment of inflammations with greater safety. Herein, the essential oils of bitter orange leaf extract (Citrus aurantium) were characterized via GC-MS, whereby, Linalyl acetate was the most major compound was isolated using column chromatography and identified by NMR analysis. The in vivo inflammation inhibition activity against carrageenan-induced models, and central analgesic effect as well as antipyretic potentiality of linalyl acetate were evaluated in rats. The administration of linalyl acetate (100 and 200 mg/kg) exhibited significant fast onset not long-standing anti-inflammatory effect in rat paw edema model in dose-dependent manner, compared to the control and reference drug. This significant inflammation reduction were supported by improving the antioxidant status of the paw via reduction of malondialdehyde (MDA) level and restoration of glutathione (GSH) levels as well as attenuation of proinflammatory cytokines levels (TNF-α), IL-1b, prostaglandin E2 (PGE2), and COX-2 in paw tissues. Although, the oral administration of linalyl acetate (100 and 200 mg/kg) has minimal analgesic it has potent long-lasting antipyretic activity in rats. The higher dose of linalyl acetate (200 mg/kg) displayed fast-onset anti-inflammatory activity better than the reference drug. Furthermore, linalyl acetate (200 mg/kg) has the best antipyretic activity. These findings shed light on promising medicinal uses of linalyl acetate against numerous inflammatory and hyperthermia ailments that could be attributed to its active constituents.

Attrition of methylnaltrexone treatment-emergent adverse events in patients with chronic noncancer pain and opioid-induced constipation: a post hoc pooled analysis of two clinical trials.

Background: Opioids prescribed for the management of chronic noncancer pain are associated with nausea, vomiting, and constipation. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, has demonstrated robust efficacy and was well-tolerated in treating opioid-induced constipation without affecting central analgesia. Our objective was to assess changes in the frequency of treatment-emergent adverse events (TEAEs) after the first or second dose of methylnaltrexone or placebo. Methods: This post hoc analysis pooled data from two randomized, placebo-controlled clinical trials assessing methylnaltrexone for opioid-induced constipation in the outpatient setting. Patients received subcutaneous methylnaltrexone (12 mg once daily or 12 mg once every other day), oral methylnaltrexone (150, 300, or 450 mg daily), or placebo. TEAEs, opioid withdrawal symptoms, pain intensity, and rescue-free bowel movements (RFBMs) within 4 hours of the first dose (i.e., RFBM responders) were assessed. Associations between TEAE frequencies and RFBM response were also evaluated. Results: The analysis included 1263 adult patients with chronic noncancer pain. TEAE rates declined from treatment day 1 to 2 (methylnaltrexone: 16.2%-5.3%; placebo: 6.6%-5.4%). Among methylnaltrexone-treated patients, significantly greater proportions of RFBM responders versus nonresponders reported gastrointestinal TEAEs on day 1. No associations between RFBM response and the frequency of TEAEs were observed in the placebo group. No meaningful changes in opioid withdrawal symptoms or pain intensity were observed. Conclusions: Early-onset TEAEs following methylnaltrexone treatment, particularly gastrointestinal TEAEs, are at least partially due to laxation. Methylnaltrexone treatment effectively relieves opioid-induced constipation without affecting the central analgesic effects of opioids.

Neuropharmacological assessment of the methanolic stem back extract of Anopyxis klaineana (Pierre) Engl. (Rhizophoraceae) in mice

BackgroundMedicinal plants have recently attracted attention on a global scale for therapeutic interventions in the field of neuroscience. Anopyxis klaineana, a medicinal plant widely used in West Africa, has been studied extensively for its anti-inflammatory effects. However, studies on its neuropharmacological effects are quite limited. This study therefore assessed the neuropharmacological potential of the methanolic stem bark extract of Anopyxis klaineana (EAK) in murine models. Materials and methodsMice were treated orally with a methanolic stem back extract of Anopyxis klaineana (EAK) at 10, 30 or 100 mg/kg followed by testing in the elevated plus-maze (EPM) and open field (OF) tests for anxiolytic-like effects. EAK's antidepressant-like potential was also evaluated in the tail suspension test (TST), while anticonvulsant and central analgesic effects were evaluated with the pentylenetetrazol (PTZ)-induced convulsion threshold and tail withdrawal tests respectively at 30, 100 or 300 mg/kg. The extract was additionally subjected to chromatographic analyses using high resolution HPLC-MS. ResultsTotal ion current chromatogram of EAK revealed several peaks suggestive of secondary metabolites of the plant extract. EAK significantly (p<0.05) reduced depression-like behaviours in the TST although not as potent as fluoxetine (ED50: EAK=43.39±2.5; fluoxetine=1.16±1.6) (F3,20=9.663, p = 0.0004). It also showed significant anticonvulsive effect by reducing the frequency and duration of PTZ-induced convulsions (ED50=48.53±2.5 mg/kg) (F3,19=5.136, p = 0.0091). This anticonvulsant effect was seen in both clonic and tonic convulsions at 30 and 300 mg/kg. Additionally, EAK-treated mice showed higher latency to tail withdrawal in the analgesia test. We also observed significant (p<0.05) dose-dependent increase in anxiolytic-like effects in EAK-treated animals in the EPM (F3,20=10.77, p = 0.0002) and OF tests (F3,22=5.079, p = 0.008). ConclusionsThe methanolic Anopyxis klaineana stem back extract exhibits anxiolytic-like, antidepressant-like, analgesic and anticonvulsant effects in murine models for assessing neuropharmacological activity and is a good source for novel neuroactive compounds.

Synergistic anti-inflammatory and analgesic activity of hydroethanolic extracts of Terminalia macroptera Guill. &amp; Perr. and Ximenia americana L.

Inflammation is the reaction of the immune system to an external or internal aggression of the organism. The symptoms (redness, edema, heat and pain) are secondary to the increase in vascular permeability. The hydroethanolic extract of and has anti-inflammatory properties in vitro. The aim was to examine the anti-inflammatory and analgesic activities of extracts alone and in combination. The anti-inflammatory activity was studied using the carragenan-induced paw edema and the type of interactions between the two extracts was determined by the combination index and on the isobologram. Acetic acid-induced torsion and Haffner's tail clamp test were performed to evaluate the analgesic activity. At a dose of 500 mg/kg, a and extracts showed a percentage of inhibition of 57.02% and 56.53% respectively. The Median-Effective Dose of combination 2 (174.02 mg/kg) was better than that of combination 1 (186.03 mg/kg). The combination index and isobologram indicated a synergistic interaction between the constituents of the two combinations. The extract of , and the combination at the dose of 500 mg/kg reduced the number of twists by 46.42; 50.17 and 65.53% respectively. The central analgesic response of the combination was maximal (37.36 ± 8.15 seconds) 60 min after administration. The extracts alone showed anti-inflammatory activity and the combinations showed a synergy of effects. The combination showed peripheral and central analgesic effects.

The Pharmacokinetics of Subcutaneous Methylnaltrexone Bromide in Rhesus Macaques (Macaca mulatta).

Opioids are an integral component of pain management for nonhuman primates. These potent analgesics also adverse gastrointestinal (GI) effects that include constipation, bloating, and delayed gastric emptying. Methylnaltrexone bromide (MNTX) is a selective, peripherally acting μ- and κ-opioid receptor antagonist that can be used to mitigate the GI effects associated with opioid administration. Unlike naltrexone, a similar drug in this class, MNTX possesses an N-methyl-quaternary amine group that prevents it from crossing the blood brain barrier. This blockage allows inhibition of peripheral GI opioid receptors without affecting opioid-mediated analgesia in the central nervous system. We conducted a pharmacokinetic analysis of MNTX in serum and CSF of 6 healthy juvenile male rhesus macaques after subcutaneous administration of a 0.15-mg/kg dose. We hypothesized that the macaques would demonstrate a Tmax of 0.5 h, similar to that of humans, and that no MNTX would be detected in the CSF. This treatment resulted in a peak serum concentration of 114 ± 44 ng/mL at 0.25 ± 0.00 h; peak CSF at concentrations were 0.34 ± 0.07 ng/mL at the Tmax. These data show that subcutaneous administration of MNTX to rhesus macaques may block peripheral adverse effects of opioids without interfering with their central analgesic effects.

Acute toxicity, analgesic and anti-inflammatory effects of soursop leaf ethanol extract (Annona muricata l.) in vivo

This study tested the peripheral analgesic effect of leaf extract by injecting 1% acetic acid on the peritoneum of white mice; tested the central analgesic effect by dipping the mice's tail in hot water (52 ± 0.5) °C; tested the acute anti-inflammatory effect by injecting carrageenan into the paws of mice causing edema; tested the chronic an- ti-inflammatory effect by injecting Freund's complete adjuvant (FCA) into the paws of mice causing edema. The control drugs used in the trials were diclofenac and codeine. Result: LD50 of the Annona muricata leaf ethanol extract was 0.705 mg/kg; The study showed that at all 3 doses, 35 mg/kg, 70 mg/kg and 140 mg/kg Annona muricata leaf extract had anti-inflammatory effects on acute and chronic inflammation; central and peripheral analgesic effects on mice.

The analgesic and anti-inflammatory effects of soursop leaf ethanol extract of Gnetum montanum Markgr. in vivo

This study was conducted to investigate evaluate the anti-inflammatory and analgesic effects of Gnetum montanum Markgr. extract. Methods: the anti-inflammatory effect was studied in two models of carragenin-in- duced paw edema and FCA-induced edema; the analgesic effect was studied on the model of colic pain and the Tail-immersion method. Results: In addition, the study also showed that at all 3 levels of tested doses, 150mg/kg, 250mg/kg and 500mg/kg Gnetum montanum Markgr extract exhibited acute and chronic anti-inflammatory effects, central analgesic and anti-inflammatory effects peripheral in experimental animals.