Influence of Substrate Location and Temperature Variation on the Growth of ZnO Nanorods Synthesized by Hot Water Treatment.

Hot water treatment (HWT) is a versatile technique for synthesizing metal oxide nanostructures (MONSTRs) by immersing metal substrates in hot water, typically in glass beakers. The proximity of substrates to the heat source during HWT can influence the temperature of the substrate and subsequently impact MONSTR growth. In our study, zinc (Zn) substrates underwent HWT at the base of a glass beaker in contact with a hot plate and at four different vertical distances from the base. While the set temperature of deionized (DI) water was 75.0 °C, the substrate locations exhibited variations, notably with the base reaching 95.0 °C. Scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and Raman spectroscopy showed stoichiometric and crystalline zinc oxide (ZnO) nanorods. ZnO rods on the base, exposed to higher temperatures, displayed greater growth in length and diameter, and higher crystallinity. Nanorods with increasing vertical distances from the base exhibited a logarithmic decrease in length despite identical temperatures, whereas their diameters remained constant. We attribute these findings to crucial HWT growth mechanisms like surface diffusion and "plugging", influenced by temperature and water flow within the beaker. Our results provide insights for optimizing synthesis parameters to effectively control MONSTR growth through HWT.

Comparative Experimental Study of using Tramadol & Nefopam in Pain Management.

BACKGROUND: Pain is a disturbing sensory and emotive sentiment triggered mainly by tissue-damaging stimuli. This study aimed to evaluate the potential effect of tramadol and nefopam on acute pain. METHODS: Thirty Sprague-Dawley rats (each 200-250 g) were randomly allocated into three sets (n=10). The nefopam group was treated with nefopam (3.5 mg/kg) by intraperitoneal (IP) injection; the tramadol group was given tramadol (50mg/kg) by IP injection, and the control group was treated with normal saline. Two main methods were proposed for assessing and monitoring rat pain: hot plate and tail-flick techniques using tail immersion. RESULTS: It was revealed a significant change (p<0.0001) in the outcome in the animal groups that received nefopam (3.5mg/kg/IP) and tramadol (50mg/kg/IP) in the prospect of hot plate test (hand paw lick parameter) and tail flick test. Regarding the hot plate test (jumping parameter), there was no significant change (p>0.05) in animals treated with tramadol and nefopam compared to the control group. Moreover, a considerable difference between the hot plate test (hand paw lick parameter) and the tail-flick test was detected between tramadol and nefopam-treated groups. However, no significant variance (P=0.101) was detected between the two groups in the hot plate test (jumping parameter). CONCLUSION: Tramadol showed better analgesic activity over nefopam in suppressing pain stimuli in acute settings with modest to severe pain, making tramadol a favourable choice for short-term management of postoperative pain.

Evaluation of anti-nociceptive and anti-inflammatory activities of solvent fraction of the roots of Echinops kebericho Mesfin (Asteraceae) in mice model.

OBJECTIVE: The present study was aimed at investigating the antinociceptive and anti-inflammatory activities of the solvent fractions of the roots of Echinops kebericho Mesfin in rodent models of pain and inflammation. METHODS: Successive maceration was used as a method of extraction using solvents of increasing polarity: methanol and water. Ethyl acetate, chloroform and distilled water were used as solvents of the fraction process. Swiss albino mice models were used in acetic acid induced writhing, hot plate, carrageenan induced paw edema and cotton pellet granuloma to assess the analgesic and anti-inflammatory activities. The test groups received different doses (100 mg/kg, 200 mg/kg and 400 mg/kg) of the three fractions (chloroform, ethyl acetate and aqueous). The positive control groups received ASA (150 mg/kg) for the writing test, morphine (10 mg/kg) for the hot plate method, diclofenac Na for carrageenan-induced paw edema, and dexamethasone (10 mg/kg) for granuloma, while the negative control group received distilled water. RESULTS: EA fraction at all test doses employed (100 mg/kg, 200 mg/kg, and 400 mg/kg) showed statistically significant (p<0.05, p<0.01, p<0.001 respectively) analgesic and anti-inflammatory activities in a dose-dependent manner. The AQ fraction on the other hand produced statistically significant (p<0.05, p<0.012) analgesic and anti-inflammatory activities at the doses of 200 mg/kg and 400 mg/kg, while the CH fraction exhibited statistically significant (p<0.05) analgesic and anti-inflammatory activity at the dose of 400 mg/kg. CONCLUSIONS: In general, the data obtained from the present study elucidated that the solvent fractions of the study plant possessed significant analgesic and anti-inflammatory activities and were recommended for further investigations.

Investigation of the effectiveness of atmospheric pressure cold plasma on sciatic nerve injury in rats.

BACKGROUND: The aim of this study was to evaluate the efficacy of atmospheric pressure cold plasma jet and plasma activated medium (PAM) on sciatic nerve injury (SNI). MATERIALS AND METHODS: Rats were divided into 6 groups (n = 10); group 1 (Sham), group 2 (SNI), group 3 (SNI + Atmospheric pressure cold plasma jet 5 min), group 4 (SNI + Atmospheric pressure cold plasma jet 10 min), group 5 (SNI + PAM 5 min), group 6 (SNI + PAM 10 min). On the 1st, 8th, 15th, 22nd days of the study, atmospheric pressure cold plasma jet was applied to rats in groups 3 and 4, and PAM was applied to rats in groups 5 and 6. Hot plate test was applied to all rats on the same days. On day 28, the experiment was terminated and sciatic nerve tissues were removed for histopathologic evaluations. RESULTS: According to the 4-week average of the hot plate tests, a significant relationship was found between group 2 and group 4 and group 6 (p < 0.05). When evaluated within each week, significant differences were found between group 2 and group 4 in week 1, between group 2 and group 5 and group 6 in week 2, between group 2 and group 4 in week 3, and between group 2 and group 4 and group 6 in week 4 (p < 0.05). As a result of histopathologic analysis, except for the control group, the other groups had similar characteristics in terms of axonal degeneration, periaxonal swelling and axon density. CONCLUSIONS: As a result of our study, we found that plasma application showed an improvement in the duration of the hot plate test, but did not show any improvement histopathologically.

Isolation, invitro, invivo anti-inflammatory, analgesic and antioxidant potential of Habenaria plantegania Lindl.

Habenaira plantaginea belong to orchid family which is native to Asia. Members of this family are commonly famous for the cure of pain and inflammation. To date, no research was found on isolation of compounds from this plant for the treatment of inflammation and analgesia nor has been published to our knowledge. The purpose of this study was to evaluate an analgesic, anti-inflammatory and anti-oxidant activity of the isolated compound from the most potent chloroform sub-fraction and the isolated compounds form the habenaria plantaginea. Anti-inflammatory analgesic and antioxidant potential of the various chloroform sub-fractions and isolated compounds from the most potent sub-fraction (HP-1 & HP-1) were screened for their in vitro enzymatic assays. Furthermore, prior to in-vivo investigation, the isolated compounds were subjected for their toxicity study. The potent compound was then examined for acetic acid-induced writhing, hot plate test, carrageenan-induced inflammation assays. Further various phlogistic agents were used for the evaluation of mechanism. In the COX-2 inhibitory assay the chloroform sub fraction Cf-4 demonstrated excellent activity as compared to the other sub-fraction with 92.15% inhibition. The COX-2 enzyme make prostaglandins which are directly involved in inflammation. Likewise against 5-LOX the Cf-4 was the most potent sub-fraction with IC50 3.77 µg/mL. The 5-LOX catalyzes the biosynthesis of leukotrienes which is a group of lipid mediators of inflammation derived from arachidonic acid. Free radicals can induce inflammation through cellular damage while chronic inflammation generates a large number of free radicals, whose eventually lead to inflammation. In antioxidant assays the Cf-4 fraction was displayed excellent results against ABTS, DPPH and H2O2 free radical with 88.88, 77.44, and 65.52% inhibition at highest concentration. Likewise, the compound HP-1 demonstrated 88.81, 89.34 and 80.43% inhibition while compound HP-2 displayed 84.34, 91.52 and 82.34% inhibition against ABTS, DPPH and H2O2 free radical which were comparable to the standard drug ascorbic acid respectively. This study's findings validate the use of this species as traditional use.

Effects of inhibition of Nav1.3, Nav1.7, and Nav1.8 channels on pain-related behavior in Speke's hinge-back tortoise (Kinixys spekii).

Comparative studies using reptiles as experimental animals in pain research could expand our knowledge on the evolution and adaptation of pain mechanisms. Currently, there are no data reported on the involvement of voltage-gated sodium ion channels on nociception in reptiles. The aim of this study was to investigate the involvement of Nav1.3, Nav1.7, and Nav1.8 ion channels in nociception in Speke's hinge-back tortoise. ICA 121341 (selective blocker for Nav1.1/Nav1.3), NAV 26 (selective blocker for Nav1.7), and A803467 (selective blocker for Nav1.8) were used to investigate the involvement of Nav1.3, Nav1.7, and Nav1.8, respectively. The chemicals were administered intracoelomically thirty minutes before the start of nociceptive tests. ICA 121341 did not cause a significant decrease in the time spent in pain-related behavior in all the nociceptive tests. NAV 26 and A8034667 caused a statistically significant decrease in the mean time spent in pain-related behavior in the formalin and capsaicin tests. Only A803467 caused a statistically significant increase in the mean latency to pain-related behavior in the hot plate test. NAV 26 and A803467 had no observable side effects. In conclusion, Nav1.7 and Nav1.8 are involved in the processing of chemically induced inflammatory pain in Speke's hinge back tortoise. In addition, Nav1.8 are also significantly involved in the development of thermal-induced pain-related behavior in this species of reptile. However, our results do not support the involvement of Nav1.3 on the development of chemical or thermal induced pain-related behavior in the Speke's hinge back tortoise.

Experimental and Theoretical Studies of the Thermal Contact Conductance for Bundles of Round Steel Bars.

The paper presents investigations devoted to the analysis of the thermal contact conduction in a bundle of round steel bars. The phenomenon can be expressed quantitatively with the use of thermal contact conductance (hct). The starting points for the presented analysis were the results of the experimental measurements of the effective thermal conductivity. The measurements were performed for samples of a medium in the form of flat packed beds of bars with three different arrangements: staggered, in-line, and crossed and four bar diameters: 10, 20, 30, and 40 mm. Next, a mathematical model was developed, thanks to which the values of the hct coefficient were calculated for the analyzed cases. This approach consists in analyzing thermal resistances in the medium model, which is defined with an elementary cell. It was established that the value of the hct coefficient in the temperature range of 50-600 °C changes within the range of 50-175 W/(m2·K), and it decreases with an increase in the bar diameter. The final effect of the present study was to develop generalized approximation equations describing changes in thermal contact conductance in the heated bar bundle simultaneously in the temperature and bar diameter function.

In-vitro and in-vivo assessment of the anti-diabetic, analgesic, and anti-inflammatory potenstials of metal-based carboxylates derivative.

In the current research work, an amide based metal carboxylate chemical ([((5-((5-(2-hydroxyethyl)-4-methylthiazol-3-ium-3-yl)methyl)-2-methylpyrimidin-4-yl)amino)bis((4-((4-methoxy-2-nitrophenyl)amino)-4-oxobutanoyl)oxy)zinc]) was identified as anti-diabetic analgesic and anti-inflammatory. The identified chemical(MT-1) was tested for acute toxicity (the MT-1 was fund safe), antidiabetic analgesic, and anti-inflammatory potentials. The in-vitro study was conducted for antidiabetic enzyme inhibition (α-amylase and α-glucosidase) and the in-vivo studies included analgesic (acetic acid-induced writing and hot plate model) and anti-inflammatory (carrageenan etc induced edema) effects. The tested compound showed 88.63% (IC50 = 3.23 µg/ml) and 89.10%(IC50 = 5.10 µg/ml) againstα-amylase and α-glucosidase respectively. A significant (p < 0.001) analgesic effect was noted by MT-1 in acetic acid-induced animal models with a percent effect of 86.00, 60.,06, and 55.29 at the tested doses of 20, 1,0, and 5 mg/kg respectively. In the case of the hot plate model, the MT-1 showed a significant (p < 0.001) effect with maximum percent prolongation in latency observed after 60 min.08, 22.2,9, and 11.61) against 20, 1,0, and 5 mg/kg. The analgesic effect in the hot plate model was significantly (p < 0.01) reversed by the injection of naloxone (0.125 mg/kg). The paw edema induced by carrageenan, histamine, bradykinin, arachidonic acid, and PGE2 was significantly antagonized with percent attenuation of 34.09, 33.57, 34.60, 34.14, and 48.04 respectively. Furthermore, to predict the interactions between the MT-1 compound and COX-2 molecular docking was carried out and the result was compared with the standard compound. The docking score of MT-1 was predicted as -6.30 while that of Diclofenac was predicted as -6.82. Both compounds made several hydrogen bond interactions with the active site of the COX-2 enzyme. The docking study revealed the potent inhibitory potential of the compound MT-1 against the COX-2 receptor.

A simple method to account for thermal boundary layers during the estimation of CTmax in small ectotherms.

As temperatures rise, understanding how ectotherms will become impacted by thermal stress is of critical importance. In this context, many researchers quantify critical temperatures - these are the upper (CTmax) and lower (CTmin) thermal limits at which organisms can no longer function. Most studies estimate CTs using bath-based methods where organisms are submerged within a set thermal environment. Plate-based methods (i.e. hot plates), however, offer huge opportunity for automation and are readily available in many lab settings. Plates, however, generate a unidirectional thermal boundary layer above their surface which means that the temperatures experienced by organisms of different sizes is different. This boundary layer effect can bias estimates of critical temperatures. Here, we test the hypothesis that biases in critical temperature estimation on hot plates are driven by organism height. We also quantify the composition of the boundary layer in order to correct for these biases. We assayed four differently sized species of UK ants for their CTmax in dry baths (with no boundary layer) and on hot plates (with a boundary layer). We found that hot plates overestimated the CTmax values of the different ants, and that this overestimate was larger for taller species. By statistically modelling the thickness of the thermal boundary layer, and combining with estimates of species height, we were able to correct this overestimation and eliminate methodological differences. Our study provides two main findings. First, we provide evidence that organism height is positively related to the bias present in plate-based estimates of CTmax. Second, we show that a relatively simple statistical model can correct for this bias. By using simple corrections for boundary layer effects, as we have done here, researchers could open up a new possibility space in the design and implementation of thermal tolerance assays using plates rather than restrictive dry or water baths.

Measurement Methods of the Thermal Resistance of Materials Used in Clothing.

This paper describes methods for evaluating the thermal properties of textile materials, clothing composites, and clothing using an integrated measurement system that includes a hot plate, a multi-purpose differential conductometer, a thermal manikin, a temperature gradient measurement device, and a device for measuring the physiological parameters of the human body during the exact evaluation of garment thermal comfort. In practice, measurements were taken on four types of materials widely used in the production of conventional and protective clothing. The measurements were carried out using a hot plate and a multi-purpose differential conductometer, determining the thermal resistance of the material both in its uncompressed form and when a force was applied that was ten times greater than that needed to determine its thickness. Using a hot plate and a multi-purpose differential conductometer, thermal resistances of textile materials were assessed at different levels of material compression. On hot plates, both conduction and convection had an impact on thermal resistance, but in the multi-purpose differential conductometer, only conduction did. Moreover, a reduction in thermal resistance was observed as a result of compressing textile materials.

Cannabidiol and mitragynine exhibit differential interactive effects in the attenuation of paclitaxel-induced mechanical allodynia, acute antinociception, and schedule-controlled responding in mice.

BACKGROUND: For many chemotherapy patients peripheral neuropathy is a debilitating side effect. Mitragyna speciosa (kratom) contains the alkaloid mitragynine (MG), which produces analgesia in multiple preclinical pain models. In humans, anecdotal reports suggest cannabidiol (CBD) may enhance kratom-related analgesia. We examined the interactive activity of MG and CBD in a mouse chemotherapy-induced peripheral neuropathy (CIPN) model. We also examined MG + CBD in acute antinociception and schedule-controlled responding assays, as well as examined underlying receptor mechanisms. METHODS: Male and female C57BL/6J mice received a cycle of intraperitoneal (ip) paclitaxel injections (cumulative dose 32 mg/kg). The von Frey assay was utilized to assess CIPN allodynia. In paclitaxel-naïve mice, schedule-controlled responding for food was conducted under a fixed ratio (FR)-10, and hot plate antinociception was examined. RESULTS: MG dose-relatedly attenuated CIPN allodynia (ED50 102.96 mg/kg, ip), reduced schedule-controlled responding (ED50 46.04 mg/kg, ip), and produced antinociception (ED50 68.83 mg/kg, ip). CBD attenuated allodynia (ED50 85.14 mg/kg, ip) but did not decrease schedule-controlled responding or produce antinociception. Isobolographic analysis revealed 1:1, 3:1 MG + CBD mixture ratios additively attenuated CIPN allodynia. All combinations decreased schedule-controlled responding and produced antinociception. WAY-100635 (serotonin 5-HT1A receptor antagonist) pretreatment (0.01 mg/kg, ip) antagonized CBD anti-allodynia. Naltrexone (pan opioid receptor antagonist) pretreatment (0.032 mg/kg, ip) antagonized MG anti-allodynia and acute antinociception but produced no change in MG-induced decreased schedule-controlled behavior. Yohimbine (α2 receptor antagonist) pretreatment (3.2 mg/kg, ip) antagonized MG anti-allodynia and produced no change in MG-induced acute antinociception or decreased schedule-controlled behavior. CONCLUSIONS: Although more optimization is needed, these data suggest CBD combined with MG may be useful as a novel CIPN therapeutic.

Evaluation of Analgesics and Anti-Inflammatory Activity of the Root Extract of Impatiens rothii (Balsaminaceae) in Rodents.

Background: The roots of Impatiens rothii has been used as a traditional remedy for painful conditions, rheumatism, isthmus and crural aches. However, the analgesic and anti-inflammatory properties of this plant have yet to be scientifically confirmed. The purpose of this study was to explore possible analgesic and anti-inflammatory activities 80% methanolic root extract of Impatiens rothii. Methods: To obtain the crude extract, the roots of Impatiens rothii that had been dried and ground up were macerated in 80% methanol. The analgesic activity was determined using acetic acid-induced writhing and hot plate tests in mice, whereas the anti-inflammatory activity was analyzed using carrageenan-induced paw edema model in rats. The extract was orally administered at a dose of 100, 200 and 400 mg/kg. Results: All tested doses of Impatiens rothii extract showed significant analgesic activity (p<0.05) at observations of 30 to 120 minutes compared to the negative control in the hot plate test. In acetic acid-induced writhing test all tested doses of the 80% methanol extract of Impatiens rothii significantly (p < 0.001) reduced the number of writhing. In comparison to the control group, all tested doses displayed a significant decrease in paw edema, which appeared 2-5 hours after induction (p<0.05). Conclusion: From the results of this study, it can be stated that 80% methanolic extract of Impatiens rothii possessed substantial analgesic and anti-inflammatory activities, hence providing scientific basis for the use of this plant in the treatment of pain and inflammatory diseases.

Analgesic and Anti-Inflammatory Activities of 80% Methanol Extract and Solvent Fractions of Ehretia cymosa Thonn (Boraginaceae) Leaves in Rodents.

Background: Ethnobotanical studies in various districts of Ethiopia reported that Ehretia cymosa (E. cymosa) is used for the management of headache, abdominal pain, arthritis and rheumatism. However, there is no scientific investigation done so far to confirm these traditional claims. Thus, the aim of this study was to assess the analgesic and anti-inflammatory effects of the 80% methanol extract and fractions of E. cymosa leaves. Methods: The dried and pulverized leaves of E. cymosa were soaked with 80% methanol to obtain a crude extract. Fractionation was done using chloroform, ethyl acetate and water by a soxhlet apparatus. The analgesic effects of the crude extract and solvent fractions were assessed using acetic acid-induced writhing and hot plate tests whereas anti-inflammatory activities were investigated using carrageenan-induced paw edema and cotton-pellet-induced granuloma models. Results: In all the tested doses, the 80% methanol extract and solvent fractions revealed substantial (p < 0.001) analgesic activities in acetic acid induced writhing test. In the hot plate method, all the tested doses of E. cymosa crude extract and the solvent fractions produced significant analgesic activities (p < 0.05). In the carrageenan-induced acute inflammation model, all tested doses of the crude extract and solvent fractions resulted in a significant decline in paw edema. The 80% methanol extract and solvent fractions of E. cymosa at all the tested doses significantly reduced inflammatory exudates and granuloma mass formations (p < 0.001). Conclusion: From the results of this investigation, it can be stated that 80% methanol extract, aqueous, ethyl acetate and chloroform fractions of E. cymosa exhibited considerable analgesic and anti-inflammatory activities, supporting the plant's traditional use as a remedy for a variety of painful and inflammatory conditions.

The Endogenous Cannabinoid and the Nitricoxidergic Systems in the Modulation of Stress Responses.

The effects on stress-induced analgesia (SIA) from endogenous cannabinoid system (ECS) and nitric oxide (NO) interaction after 1 h of restraint stress were evaluated in male Wistar rats. The animals were subjected to 1 h of restraint and then injected with different combinations of cannabinoid receptor type 1 agonist anandamide (AEA) or antagonist AM251 along with an NO donor, NO precursor, or inhibitor of NO synthase. Nociception was evaluated using paw pressure (PP) or hot plate (HP) tests. AEA was administered immediately after the end of restraint-SIA (r-SIA). Administration of NO precursor reversed the pronociceptive effect of the CB1 agonist on r-SIA. Both the CB1 antagonist and the NOS inhibitor neutralized the pro-analgesic effect of L-arginine (L-arg). Administration of an NO donor, instead, increased r-SIA. Our experiments confirmed that the endogenous cannabinoid and the NO-ergic systems interact in the modulation of r-SIA. This interaction probably implies NO as a second messenger of the ECS.

Experiences and reflections about behavioral pain assays in laboratory animals.

Pharmacological assays based on the measurement of nociceptive responses in laboratory animals are a fundamental tool to assess analgesic strategies. During our experience with this type of experiments, we have been repeatedly challenged by different concerns related to their interpretation or relevance. Although these subjects are frequently discussed in our lab, they do not usually find a place in research articles with original data, in which the focus on results seems mandatory. In the present manuscript we try to discuss as central issues some of these aspects that often cross transversally our research. We have gathered them in five topics inspired by the results obtained in our laboratory. The two initial sections are devoted to the influence of the behavioral method used to assess nociception on the results achieved, as well as to the possibility that data may be more easily accepted when obtained with standard methods than with alternative ones. The third topic is related to the difficulties encountered when working with a molecule that may evoke dual effects, acting as pronociceptive or antinociceptive depending on the dose. The fourth point deals with the situation in which a particular hyperalgesic reaction is related to several molecules but the single inhibition of only one of them can completely prevent it. Finally, the last issue is addressed to comment the impact in the progress of pain research of experiments performed in animal models of pathological settings.

Thermal antinociceptive responses to alcohol in DBA/2J and C57BL/6J inbred male and female mouse strains.

BACKGROUND: The phenomenon of alcohol analgesia and tolerance can facilitate misuse and lead to the development of alcohol use disorder (AUD). Numerous alcohol-induced behaviors are genetically influenced; however, it is unknown if alcohol analgesia has a genetic contribution. Rodent studies have shown that alcohol responses differ vastly between two widely studied inbred strains of mice, C57BL/6 J (B6) and DBA/2 J (D2). Here, we used B6 and D2 mice as an initial behavioral genetic analysis of acute alcohol-induced antinociception. METHODS: The antinociceptive effect of orally-administered alcohol was characterized using the hot plate test in B6 and D2 mice of both sexes. Using the opioid receptor antagonist naloxone, the involvement of the opioid system was assessed. Locomotor activity and blood alcohol concentrations were also measured. Ovariectomized mice were used to evaluate the influence of ovarian sex hormones on alcohol-induced antinociception. RESULTS: Alcohol induced an antinociceptive effect in B6 and D2 male mice in a time- and dose-dependent manner. In addition, D2 male mice were more sensitive to the antinociceptive effect of alcohol than B6 male mice. However, locomotion is not impeded by the tested doses of alcohol in B6 mice. Female D2 and B6 mice failed to show significant antinociceptive effects in alcohol dose-response studies. In addition, alcohol-induced antinociception was still not evident in ovariectomized female mice. Male mice of both strains developed tolerance to this effect after repeated administration of alcohol. Strain differences were found in blood alcohol concentration. Finally, no difference was found in the blockade of alcohol antinociception by 2 mg/kg naloxone. CONCLUSION: Our results indicate that the antinociceptive effects of alcohol in the hot plate test are influenced by strain and sex. These findings support further genetic analysis of alcohol-induced antinociception to identify operative mechanisms and better assess the contribution of this phenotype to AUD.

Anti-Inflammatory and Analgesic Activity of Methanolic Root Extract of Verbascum sinaiticum Benth.

Introduction: Pain in its various forms is undoubtedly the most common ailment known to human beings. Non-steroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics are widely used to treat pain. However, long-term use of NSAIDs and opioids causes serious adverse effects on various organs. As a result, looking for drugs with better efficacy and lesser adverse effects appears crucial. For this purpose the obvious search begins from traditional medicines, particularly herbs. Therefore, this study investigated analgesic and anti- inflammatory activity of 80% methanol root extract of Verbasicum sinaiticum Benth (VS) in vivo. Methods: The dried and crushed plant material was macerated with 80% methanol sequentially and dried with lyophilizer. As per the acute toxicity study conducted elsewhere, 100 mg/kg, 200 mg/kg and 400 mg/kg doses of extract were used in the acetic acid induced writhing, hot plate test, as well as carrageenan and formalin induced anti-inflammatory models. As a positive control, aspirin 150 mg/kg was used for anti-nociceptive and anti-inflammatory model and morphine 10 mg/kg was used for central analgesic models. Results: VS200 and VS400 doses of the extract significantly (p< 0.05) reduced acetic acid induced writhing as compared with the control group. Similarly in hot plate test also, both VS200 and VS400 groups demonstrated significant (p< 0.05 at 30 min and p< 0.001 at 60 and 120 min) analgesic effect in comparison with the control and VS100 groups. Furthermore, in carrageenan and formalin induced anti-inflammatory test both VS200 and VS400 were shown to produce significant (p< 0.05) anti-inflammatory effect at the later hours and days. Conclusion: The findings from this study suggest that 80% methanol root extract of V. sinaiticum possesses peripheral and central analgesic as well as anti-inflammatory activity, possibly emanating from the phytochemicals present in the hydroalcoholic crude extract.

Effects of Azadirachta indica on neuropathic pain induced by chronic constriction injury to sciatic nerve of Wistar rat.

Objective: The research was designed to assess the consequences of Azadirachta indica aqueous leaf extract (AILE) on neuropathic pain in Wister rats and the role of the ATP-dependent potassium channel (KATP) as an underlying mechanism. Materials and Methods: This experimental layout was conducted on Wistar rats (n = 120) having 150 to 200 gm of body weight. On the foundation of the experimental design, rats were divided into group I (normal saline, 5 ml/kg/body weight) and group II (sham surgery and treatment with NS), group III [chronic constriction injury (CCI) in the sciatic nerve; and treated with NS], group IV (CCI and treated with AILE 400 mg/kg body weight), Group V (CCI, pretreated with Glibenclamide 15 mg/kg followed by treated with AILE 400 mg/kg). All the treatments were given once daily for a consecutive 21 days via the oral route, except Glibenclamide. Glibenclamide was given once through the intraperitoneal route on the day of the experiment. Results: Based on the neuropathic pain evaluation test, all groups were again sub-divided into subgroup "a" (walking tract analysis), "b" (cold tail immersion test), "c" (Von Frey test), and "d" (hot plate test). AILE showed a significantly higher sciatic functional index (p < 0.05) in walking track analysis, tail flick latency (p ≤ 0.05) in the cold tail immersion test, and paw withdrawal threshold (p ≤ 0.05) in the Von Frey test compared to CCI control. In addition, a nonsignificant difference in all these above-mentioned variables between the rats with CCI plus AILE and the CCI plus AILE plus glibenclamide group indicated that the KATP channel was not involved in the beneficial analgesic effects of AILE. Conclusions: The outcome of the present study indicates that AILE prevented worsening of neuropathic pain after chronic constriction injury in the sciatic nerve of Wistar rats in which the KATP channel was not involved.

Acute and Chronic Pain Preclinical Models to Study the Analgesic Properties of Melatonergic Compounds.

Melatonin (MLT) has been implicated in several pathophysiological states, including pain. MLT mostly activates two G protein-coupled receptors, MT1 and MT2. MLT displays analgesic properties in several animal paradigms of acute, inflammatory, and neuropathic pain. Although the analgesic mechanism of action of MLT is not yet completely elucidated, there is strong preclinical evidence suggesting the pharmacological potential of melatonergic compounds for treating pain. Importantly, MLT and melatonergic compounds seem to have a favorable toxicological profile than currently approved analgesic drugs. These compounds may thus deserve to be further developed as novel analgesic drugs, but this process relies on the use of appropriate and standardized experimental procedures. Therefore, in this chapter, we present the methodology to study the analgesic properties of MLT and melatonergic drugs in a preclinical model of chronic and acute pain. In addition to technical details of the surgical technique, details of anesthesia and perioperative care are also included.

Expression of oxytocin in hypothalamus and reduction of nociceptive stress following administration of Kamikihi-to in female rats.

Hypothalamo-neurohypophysial oxytocin (OXT) plays an essential role in reproduction and in several socio-physiological functions, including stress reduction, anxiety relief, feeding suppression, social recognition, and trust building. Recent studies suggest that the central OXT system is also involved in antinociceptive and anti-inflammatory functions. Kamikihi-to (KKT), a Japanese traditional herbal (Kampo) medicine composed of 14 herbal ingredients, is clinically prescribed for patients with psychological symptoms, including anxiety, depression, and insomnia, and it has been associated with OXT expression. We investigated the antinociceptive response and OXT expression according to sex and the effects of KKT pre administration in a rat model. We found that nociceptive responses measured via the hot plate and formalin tests were attenuated following the administration of KKT-enriched feed for 4 weeks. The observation of mRFP1 fluorescence in OXT-mRFP1 transgenic rats revealed that KKT-administered rats showed increased expression of OXT in the magnocellular and parvocellular paraventricular nucleus of the hypothalamus. Food intake in the KKT-pre-administered group significantly decreased after cholecystokinin (CCK)-8 administration. Our results suggest that KKT is involved in the attenuation of nociceptive stress in female rats by enhancing the expression of OXT in the hypothalamus.