Animal Paw Research Articles

In vivo analgesic, anti-inflammatory and molecular docking studies of S-naproxen derivatives

In the current studies two naproxen derivatives (NPD) were evaluated for analgesic and anti-inflammatory properties. The acetic acid and hot plate animal models were used to screen the compounds for analgesic potential. While the anti-inflammatory potential was evaluated through animal paw edema, induced by several inflammatory mediators (carrageenan, bradykinin, and prostaglandin E2), the xylene-induced ear edema was also used as an inflammatory model. Both NPDs showed significant (p < 0.001) antinociceptive effects in the acetic acid-induced writhing paradigm. In the case of the hot plate, the NPD 1 at the tested dose of 5 mg/kg enhanced the latency time after 60 min of injection, which remained significant (p < 0.001) up to the end of the experiment duration. The maximum percent inhibition of NPD 1 was 87.53. The naloxone injection significantly lowered the latency time of NPD 1 as compared to NPD 2. Regarding the anti-inflammatory effect, both of the tested NPDs demonstrated a significant reduction in paw edema against various inflammatory mediators, as mentioned above; however, the anti-inflammatory effect of NPD 1 was better. The maximal percent inhibition by NPD 1 and 2 was 43.24 (after 60 min) and 45.93 (after 90 min). A considerable effect also resulted from xylene-induced ere edema. Further, a molecular docking study was carried out to investigate the binding modes of the NPD. The docking analysis revealed that the NPD significantly interacted with the COX2 enzyme. Furthermore, molecular dynamics simulation was carried out for the docked complexes. The MD simulation analysis revealed the high stability of the two naproxen derivatives.

Anti-arthritic effect of chicken embryo tissue hydrolyzate against adjuvant arthritis in rats (X-ray microtomographic and histopathological analysis).

Finding new, safe strategies to prevent and control rheumatoid arthritis is an urgent task. Bioactive peptides and peptide‐rich protein hydrolyzate represent a new trend in the development of functional foods and nutraceuticals. The resulting tissue hydrolyzate of the chicken embryo (CETH) has been evaluated for acute toxicity and tested against chronic arthritis induced by Freund's full adjuvant (modified Mycobacterium butyricum) in rats. The antiarthritic effect of CETH was studied on the 28th day of the experiment after 2 weeks of oral administration of CETH at doses of 60 and 120 mg/kg body weight. Arthritis was evaluated on the last day of the experiment on the injected animal paw using X‐ray computerized microtomography and histopathology analysis methods. The CETH effect was compared with the non‐steroidal anti‐inflammatory drug diclofenac sodium (5 mg/kg). Oral administration of CETH was accompanied by effective dose‐dependent correction of morphological changes caused by the adjuvant injection. CETH had relatively high recovery effects in terms of parameters for reducing inflammation, inhibition of osteolysis, reduction in the inflammatory reaction of periarticular tissues, and cartilage degeneration. This study presents for the first time that CETH may be a powerful potential nutraceutical agent or bioactive component in the treatment of rheumatoid arthritis.

Comparative description of the anti-inflammatory action of the food concentrate “Enoant” and resveratrol in the model of an acute exudative inflammation

The paper considers comparing the anti-inflammatory action of the food concentrate “Enoant” and a classical antioxidant – resveratrol in the doses of 20 mg/kg in the model of an acute exudative inflammatory of animals. It was proved that resveratrol had the most anti-inflammatory action; this was manifested by a considerable decrease of the increase rate of the animal paw’s size in the formalin test after 7 and 14 days of taking the antioxidant. The food concentrate “Enoant” demonstrated anti-inflammatory properties after 7 days of taking the antioxidant; this was manifested by the increase of the animal paw’s size in the formalin test, however 14 days later a moderate anti-inflammatory reaction was registered, this was manifested by the decrease of the increase rate of the animal paw’s size in the formalin test..

'Not only faces': specialized visual representation of human hands revealed by adaptation.

Classical neurophysiological studies demonstrated that the monkey brain is equipped with neurons selectively representing the visual shape of the primate hand. Neuroimaging in humans provided data suggesting that a similar representation can be found in humans. Here, we investigated the selectivity of hand representation in humans by means of the visual adaptation technique. Results showed that participants' judgement of human-likeness of a visual probe representing a human hand was specifically reduced by a visual adaptation procedure when using a human hand adaptor but not when using an anthropoid robotic hand or a non-primate animal paw adaptor. Instead, human-likeness of the anthropoid robotic hand was affected by both human and robotic adaptors. No effect was found when using a non-primate animal paw as adaptor or probe. These results support the existence of specific neural mechanisms encoding human hand in the human's visual system.

An Experimental Comparison of the Analgesic and Anti-Inflammatory Effects of Safflower Oil, Benzydamine HCl, and Naproxen Sodium.

The study aims to establish how feasible a natural therapy option (safflower oil) is in the treatment of postoperative pain. Naproxen sodium has already been experimentally proven to be effective for this purpose. Accordingly, the analgesic and anti-inflammatory effects of safflower oil were compared with those obtained with benzydamine HCl and naproxen sodium. Forty-two, healthy, adult female rats of Wistar albino species were divided at random into six groups of seven rats. The intervention allocation was as follows: Group No. 1-physiological saline 0.9%; Group No. 2-safflower oil 100 mg/kg; Group No. 3-safflower oil 300 mg/kg; Group No. 4-benzydamine HCl 30 mg/kg; Group No. 5-benzydamine HCl 100 mg/kg; and Group No. 6-naproxen sodium 10 mg/kg. Following allocation of treatment, pain was induced experimentally and tested in various ways (hot plate test, tail-pinching test, and writhing test) and the efficacy of each treatment in providing peripheral and central analgesia was evaluated. The second stage consisted of providing different treatments to four groups (groups 7-10) of seven rats each, chosen at random. The allocations were as follows: Group No. 7-physiological saline 0.9%; Group No. 8-safflower oil 300 mg/kg; Group No. 9-benzydamine HCl 100 mg/kg; and Group No. 10-naproxen sodium 10 mg/kg. To create experimental inflammation, 2% formaldehyde was injected into the experimental animal's paw and the resulting edema was measured and recorded for a 10-day period. Edema inhibition was calculated as a percentage. The rats were sacrificed and the paw and stomach dissected for histopathological examination. The data were used for statistical analysis, using the Shapiro-Wilk, Kruskal-Wallis H test, and two-way analysis of variance. In the tail-pinching test, it was determined that a 300 mg/kg dose of safflower oil shows central spinal analgesic efficacy and this effect is close in magnitude to 10 mg/kg of the reference material, naproxen sodium. In the squirming test, it was observed that the 100 and 300 mg/kg doses of safflower oil had a peripheral analgesic effect when compared with the serum physiological (placebo) group. The peripheral efficacy of 300 mg/kg safflower oil was found to approximate that of 10 mg/kg naproxen sodium. In rats treated with benzydamine HCl 100 mg/kg, similar peripheral analgesic efficacy to naproxen sodium 10 mg/kg was noted. In the hot plate test, no difference in the analgesic efficacy between the various agents was found. The change in inhibition of edema between the 1st and 10th days was most marked in rats receiving naproxen sodium 10 mg/kg. A significant difference was determined in the safflower oil 300 mg/kg and benzydamine HCl 100 mg/kg groups (P < .001). Regarding histopathology findings in the rat paw, significant differences were seen in venous congestion between placebo and safflower oil 300 mg/kg and in inflammation between the control and benzydamine HCl 100 mg/kg groups. Regarding the histopathology findings in the rat stomach, significant differences were observed in venous congestion between placebo and safflower oil 300 mg/kg; in damage to the epithelium between placebo and safflower oil 300 mg/kg and between naproxen sodium 10 mg/kg and safflower oil; and in cell infiltration and development of edema between placebo and safflower oil 300 mg/kg. It is predicted that further research into safflower oil and benzydamine HCl will create opportunities to develop analgesic-anti-inflammatory therapeutics of a novel kind for the treatment of postoperative pain and inflammation.

Factors Related to Community Knowledge of Rabies Management in Sintang, West Kalimantan

Rabies is an acute infectious disease in central nervous system which is the effect of a zoonotic virus that spread through direct contact to the wound or mucosa by infected animal saliva or paw. Rabies virus has been transmitted to human through a animal’s rabies transmitters bite like dog, car, and ape. Indonesia is a Country with a high prevalence of rabies. The low level of knowledge and lack of source of informations lead rabies prevention still become a serious problem. Purpose of this research is to knowing factors that influence society level of knowledge about rabies handling in Desa Sekubang, Sintang, West espondent. This research using descriptive quantitative correlation method with cross sectional approaches. There are 146 patriarch respondent in Desa Sekubang that has been comply inclusion criteria. The research result show that 63,7% espondent age 20-40, 49,3% respondent only studied until elementary school, 86,3% got the information from healthcare workers, 91,1% has a risk environment, and 89% have a good knowledge. Kendall’s tau-c and Chi-square correlation test statistically have a relation between age (p=0,114), education (p=0,000), environment (p=0,000), information from healthcare workers and the level of knowledge about rabies handling.Therefore this research shows the source of information from healthcare workers is very important to increase knowledge of rabies handling.

Effect of Artemisia persica Boiss essential on pain caused by chemical and thermal stimuli in mice

Introduction: Artemisia persica is an indigenous plant of Iran that has been traditionally used to relieve neurological and visceral pain. The aim of this study was to evaluate the analgesic effects of Artemisia persica essential oil on pain induced by hot plate and formalin in mice. Materials and Methods: In this experimental study, male Balb/c mice were divided into 5 groups including normal saline, Artemisia persica essential oil (50, 75 and 100 mg/kg) and morphine (10 mg/kg). The hot plate test was performed at, 15, 30, 45 and 60 minutes after the IP injection of drugs. In the formalin test, 30 minutes after the IP injection of drugs, 20 ml of 4% formalin was injected in the animal's paw and the frequency of paws licking, clopping and lifting were recorded at 0-5 (acute phase) and after injection (acute phase) and 15-30 (chronic phase) minutes. Data were analyzed by SPSS16 software. Results: Injection of Artemisia persica essential oil (75 and 100 mg/kg), 15, 30, 45 and 60 minutes before the hot plate test, significantly decreased pain threshold compared to the control group (p< 0.05) Artemisia persica essential oil at a dose of 100 mg/kg significantly decreased the frequency of paws licking, clopping and lifting at the first and second phase of formalin test (p<0.05). Conclusion: The results of this study indicate the effectiveness of Artemisia persica Boiss essential oil in relieving pain caused by chemical and thermal stimuli.

In vivo photoacoustic imaging of chorioretinal oxygen gradients.

Chorioretinal imaging has a crucial role for the patients with chorioretinal vascular diseases, such as neovascular age-related macular degeneration. Imaging oxygen gradients in the eye could better diagnose and treat ocular diseases. Here, we describe the use of photoacoustic ocular imaging (PAOI) in measuring chorioretinal oxygen saturation (CR - sO2) gradients in New Zealand white rabbits (n = 5) with ocular ischemia. We observed good correlation (R2 = 0.98) between pulse oximetry and PAOI as a function of different oxygen percentages in inhaled air. We then used an established ocular ischemia model in which intraocular pressure is elevated to constrict ocular blood flow, and notice a positive correlation (R2 = 0.92) between the injected volume of phosphate buffered saline (PBS) and intraocular pressure (IOP) as well as a negative correlation (R2 = 0.98) between CR - sO2 and injected volume of PBS. The CR - sO2 was measured before (baseline), during (ischemia), and after the infusion (600-μL PBS). The ischemia-reperfusion model did not affect the measurement of the sO2 using a pulse oximeter on the animal's paw, but the chorioretinal PAOI signal showed a nearly sixfold decrease in CR - sO2 (n = 5, p = 0.00001). We also observe a sixfold decrease in CR - sO2 after significant elevation of IOP during ischemia, with an increase close to baseline during reperfusion. These data suggest that PAOI can detect changes in chorioretinal oxygenation and may be useful for application to imaging oxygen gradients in ocular disease.

Energy-Based Pharmacophore and Three-Dimensional Quantitative Structure–Activity Relationship (3D-QSAR) Modeling Combined with Virtual Screening To Identify Novel Small-Molecule Inhibitors of Silent Mating-Type Information Regulation 2 Homologue 1 (SIRT1)

Silent mating-type information regulation 2 homologue 1 (SIRT1), being the homologous enzyme of silent information regulator-2 gene in yeast, has multifaceted functions. It deacetylates a wide range of histone and nonhistone proteins; hence, it has good therapeutic importance. SIRT1 was believed to be overexpressed in many cancers (prostate, colon) and inflammatory disorders (rheumatoid arthritis). Hence, designing inhibitors against SIRT1 could be considered valuable. Both structure-based and ligand-based drug design strategies were employed to design novel inhibitors utilizing high-throughput virtual screening of chemical databases. An energy-based pharmacophore was generated using the crystal structure of SIRT1 bound with a small molecule inhibitor and compared with a ligand-based pharmacophore model that showed four similar features. A three-dimensional quantitative structure-activity relationship (3D-QSAR) model was developed and validated to be employed in the virtual screening protocol. Among the designed compounds, Lead 17 emerged as a promising SIRT1 inhibitor with IC50 of 4.34 μM and, at nanomolar concentration (360 nM), attenuated the proliferation of prostate cancer cells (LnCAP). In addition, Lead 17 significantly reduced production of reactive oxygen species, thereby reducing pro inflammatory cytokines such as IL6 and TNF-α. Furthermore, the anti-inflammatory potential of the compound was ascertained using an animal paw inflammation model induced by carrageenan. Thus, the identified SIRT1 inhibitors could be considered as potent leads to treat both cancer and inflammation.

Evaluation of the efficacy of systemic miltefosine associated with photodynamic therapy with liposomal chloroaluminium phthalocyanine in the treatment of cutaneous leishmaniasis caused by Leishmania (L.) amazonensis in C57BL/6 mice

BackgroundThe shortage of drugs is a concern and has become the object of studies to discover effective alternatives for cutaneous leishmaniasis (CL) treatment. A topical formulation has been sought due to its low toxicity. Development of alternative therapies, such as multimodal ones, is important in confronting drug resistance. This study aims to compare the in vivo efficacy of topical photodynamic therapy (PDT) using liposomal chloroaluminium phthalocyanine (AlClPC) in the treatment of CL, isolated and associated with systemic therapy with miltefosine. MethodsFive groups were adopted, each one with six isogenic adult female mice C57BL/6: (1) Negative Control—non-infected and non-treated; (2) Positive Control (PBS)—infected and non-treated; (3) Miltefosine—infected and treated with oral miltefosine 200mg/kg/day; (4) Infected and treated with PDT with topical AlClPC (500μL) on alternate days; (5) Oral Miltefosine 200mg/kg/day and PDT with topical AlClPC (500μL) on alternate days. Therapeutic schemes lasted 20 days. Infection was confirmed by culture in Nove-McNeal-Nicolle medium (NNN) of lymph collected from the animal paw, and animals were evaluated by paw measurement and parasitological criteria. ResultsMiltefosine associated with PDT with AlClPC promoted a significant reduction in parasite number and viability when compared to the other infected groups, also returning the paw diameter to a size similar to the negative control group after 20 days of treatment. ConclusionsAssociation of miltefosine with PDT mediated by topical AlClPC represents hopes for CL treatment, an increasing dermatological disease in some countries.

Building, testing and validating a set of home-made von Frey filaments: a precise, accurate and cost effective alternative for nociception assessment.

A von Frey filament (vFF) is a type of aesthesiometer usually made of nylon perpendicularly held in a base. It can be used in paw withdrawal pain threshold assessment, one of the most popular tests for pain evaluation using animal models. For this test, a set of filaments, each able to exert a different force, is applied to the animal paw, from the weakest to the strongest, until the paw is withdrawn. We made 20 low cost vFF using nylon filaments of different lengths and constant diameter glued perpendicularly to the ends of popsicle sticks. They were calibrated using a laboratory balance scale. Building and calibrating took around 4h and confirmed the theoretical prediction that the force exerted is inversely proportional to the length and directly proportional to the width of the filament. The calibration showed that they were precise and accurate. We analyzed the paw withdrawal threshold assessed with the set of home-made vFF and with a high quality commercial set of 5 monofilaments vFF (Stoelting, Wood Dale, USA) in two groups (n=5) of healthy mice. The home-made vFF precisely and accurately measured the hind paw withdrawal threshold (20.3±0.9 g). The commercial vFF have different diameters while our set has the same diameter avoiding the problem of lower sensitivity to larger diameter filaments. Building a set of vFF is easy, cost effective, and depending on the kind of tests, can increase precision and accuracy of animal nociception evaluation.

Mannose-specific legume lectin from the seeds of Dolichos lablab (FRIL) stimulates inflammatory and hypernociceptive processes in mice

Lectins are proteins that specifically bind to carbohydrates and form complexes with molecules and biological structures containing saccharides. The FRIL (Flt3 receptor interacting lectin) is a dimeric two-chain (αβ)2 lectin presenting 67kDa molecular mass. The interaction of FRIL with carbohydrates, as determined by molecular docking, showed that this lectin has highest affinity to the carbohydrate trimannoside (−135.618MDS), followed by trehalosamine (−127.072MDS) and αα-trehalose (−121.729MDS). FRIL evoked dose-dependent paw edema, increasing animal paw volumes. The edematogenic effect of FRIL was paralleled by an increase in vascular permeability, about 10-fold higher compared to control. FRIL also significantly raised the animals flinch reaction in the first, third and fifth hours in response to mechanical stimulation. Injection of α-methyl-d-mannoside associated with FRIL inhibited edema and hypernociception. The histopathological analysis of animal paws showed a characteristically acute inflammatory process that included severe infiltration of mixed leukocytes, changes in cytoarchitecture, edema and focal areas of hemorrhage. In addition, in silico assays confirmed that FRIL preferentially interacts with trimannoside that makes up the core N-glycans cell. Therefore, our study supports the hypothesis that the lectin domain and the likely glycoconjugates containing α-d-methyl mannoside residues contribute to the inflammatory effects of FRIL.

Inflammatory and Hyperalgesic Effects of Oxidized Multi-Walled Carbon Nanotubes in Rats

We evaluated local inflammatory activity of oxidized multiwalled carbon nanotubes in rat experimental models of acute inflammation (paw edema and hyperalgesia) by analyzing their toxicity in non-mesoendothelial tissues. Subcutaneous injection of the nanotubes induced paw edema, that was maximal in the first 2 h after administration at 0.1 mg/kg (43.25 +/- 3.8 AUC) and 1 mg/kg (30.1 +/- 1.8 AUC) compared to saline (18.32 +/- 02.05 AUC). The histopathological analysis showed acute inflammation characterized by vasodilatation, edema formation, neutrophil infiltrate and tissue damage. The nanotubes also elicited hyperalgesic response, seen by the increase of animal paw withdrawal that was maximal in the first 3 hours. The data obtained at the 3rd h was: 75 +/- 9.3% (0.01 mg/kg), 58 +/- 8.3% (0.1 mg/kg) and 53 +/- 6.69% (1 mg/kg) in relation with saline (28 +/- 3.5%). In conclusion, the oxidized multiwalled carbon nanotubes elicit inflammatory and hyperalgesic effects associated to severe tissue damage in rats.

A Heretic in New Spain: Alberto Enríquez, Alias Brother Manuel de Quadros

Fray Manuel de Quadros's case was much talked about in the second half of the seventeenth century, when the Holy Inquisition of New Spain had returned to its floxedad antigua (old laziness) once the embers of the autos-da-fe that were the culmination of the persecution of practicing Jews during the Complicidad Grande (Great Complicity) had died (Inquisicion). (1) Quadros's case was truly unprecedented. For fifteen years the defendant was kept imprisoned and the inquisitors and clergymen involved were perplexed, the first proceedings begun in 1663 and Quadros's surrender to secular hands as a heretic ratified in 1678. Let us familiarize ourselves with Quadros's character and the context that formed him, since only then can we begin to intuit some of the possible motives in the trajectory that sent him to the stake, even if we may not understand his unique destiny in an era and a society in which heretics were already exceptional. Upon entering the Inquisition's jails on November 13, 1663, Quadros was un hombre de buen cuerpo, entrecano de barba, enjuto de rostro la nariz grande el pelo algo crespo la barba tambien, de edad al parecer de mas de 40 anos (a fit man, graying beard, skinny face with a large nose and somewhat curly hair and beard, apparently over forty) (Inquisicion). (2) The property confiscated from him was pitiable: an old torn book, Libro curioso, de phisonomia (curious book, about physiognomy), that dealt with the properties of things such as the herb rosemary, y tambien de experimentos (and also experiments), which included a perpetual lunar calendar; some small papers that contained little stones, fruit, and other seeds; old and dirty rags that contained pieces of ointment, dark powders, pieces of something resembling paint, little brushes, and a larger paintbrush. Eight pages that seemed to be about judiciary astrology and a little bag in the form of an animal's paw with five claws, enveloped in a sock and containing indigo ink, were also found on him. Quadros was extremely poor and his library was composed of a few booklets of quack prescriptions and pamphlets of popular astrology. In the first hearing that Quadros had before the inquisitors, he declared that he was forty-three years old, that his name was now Alberto Enriquez but had been Brother Francisco Manuel de Quadros, and that he was a member of the Franciscan order and General Confessor of the province of Lima in Peru. He said he was born in Tlaltenango, near Zacatecas, in New Spain, and took orders in Lima fourteen years ago, which he renounced only two years earlier. His trip to Peru and his return to New Spain was a veritable odyssey and an example of the mobility characteristic of some peninsular and Creole Spaniards who lived in the two great Viceroyalties of the seventeenth century, New Spain and Peru. (3) In fact, in 1621, when the prisoner was only one year old, his father suddenly abandoned Zacatecas in order to go to Peru, at that time at its peak in comparison with the situation that was beginning to affect New Spain around the same dates. Shortly thereafter, his mother and the children moved to Mexico, where the family lived until his father sent for them. His father was able to restore himself to a prosperous position in Peru. Accompanied by an uncle who also lived in Zacatecas, a black slave woman, and two black slave children, the family began an adventure which consisted of a trip by land--in sedan chairs and on the backs of Indians--and by sea, passing through Puebla, Oaxaca, Guatemala, Sonsonate, Realejo, Manta, Paita, Trujillo, Sana, and finally Callao, where they reunited with Quadros's father, who by that time had become the owner of ships and warehouses. The trip lasted a year, from the middle of 1632 until June 23, 1633, with interminable stops at various ports, as they waited for hypothetical departures. For reasons that were not stated, Quadros's father left his previous business to become the manager of the flour mill at the convent of Santa Clara in Lima. …

Participation of endogenous opioids in the antinociception induced by resistance exercise in rats

Exercise is a low-cost intervention that promotes health and contributes to the maintenance of the quality of life. The present study was designed to investigate the influence of different resistance exercise protocols on the nociceptive threshold of rats. Female Wistar rats were used to perform exercises in a weight-lifting exercise model. The following groups were examined (N = 6 per group): untrained rats (control group); an acute protocol group consisting of rats submitted to 15 sets of 15 repetitions of resistance exercise (acute group); rats exercised with 3 sets of 10 repetitions, three times per week for 12 weeks (trained group), and a group consisting of trained rats that were further submitted to the acute protocol (trained-acute group). The nociceptive threshold was measured by the paw-withdrawal test, in which the withdrawal threshold (escape reaction) was measured by an apparatus applying force to the plantar surface of the animal paw. The opioid antagonist naloxone (2 mg/kg) was administered subcutaneously 10 min before the exercise protocols. The trained group demonstrated antinociception only up to day 45 of the 12-week training period. A significant increase (37%, P < 0.05) in the nociceptive threshold was produced immediately after exercise, decreasing to 15% after 15 min, when the acute exercise protocol was used. Naloxone reversed this effect. These data show that the acute resistance exercise protocol was effective in producing antinociception for 15 min. This antinociceptive effect is mediated by the activation of opioid receptors.

Alterações morfométricas em músculo respiratório de ratos submetidos à imobilização de pata

A imobilização é um recurso frequentemente utilizado na prática clínica, sendo comum em patologias álgicas e nas fraturas. O objetivo deste estudo foi analisar a influência do processo de imobilização em músculo do sistema respiratório, o diafragma. O experimento foi efetuado com 12 ratos Wistar machos divididos em dois grupos, controle e imobilizado. O procedimento de imobilização foi realizado através de um método alternativo de imobilização por fita adesiva, sendo mantida por duas semanas. Analisou-se a morfometria das fibras do diafragma com coloração de hematoxilina e eosina. Ao compararmos o diâmetro médio das fibras musculares do diafragma dos animais imobilizados (47,15μm ± 0,329μm) em relação ao controle (54,67μm ± 0,396μm), encontramos diferença estatística entre os grupos (p &lt; 0,0001). Considerando os dados encontrados, foi possível concluir que a imobilização de pata, no modelo utilizado, foi capaz de gerar hipotrofia da musculatura respiratória, assim como um quadro geral de redução de massa corporal do animal.

Antinociceptive actions of honokiol and magnolol on glutamatergic and inflammatory pain

The antinociceptive effects of honokiol and magnolol, two major bioactive constituents of the bark of Magnolia officinalis, were investigated on animal paw licking responses and thermal hyperalgesia induced by glutamate receptor agonists including glutamate, N-methyl-D-aspartate (NMDA), and metabotropic glutamate 5 receptor (mGluR5) activator (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), as well as inflammatory mediators such as substance P and prostaglandin E2 (PGE2) in mice. The actions of honokiol and magnolol on glutamate-induced c-Fos expression in the spinal cord dorsal horn were also examined. Our data showed that honokiol and magnolol blocked glutamate-, substance P- and PGE2-induced inflammatory pain with similar potency and efficacy. Consistently, honokiol and magnolol significantly decreased glutamate-induced c-Fos protein expression in superficial (I-II) laminae of the L4-L5 lumbar dorsal horn. However, honokiol was more selective than magnolol for inhibition of NMDA-induced licking behavioral and thermal hyperalgesia. In contrast, magnolol was more potent to block CHPG-mediated thermal hyperalgesia. These results demonstrate that honokiol and magnolol effectively decreased the inflammatory pain. Furthermore, their different potency on inhibition of nociception provoked by NMDA receptor and mGluR5 activation should be considered.

Neurologic assessment of somatosensory dysfunction following an experimental rodent model of cerebral ischemia

The modified adhesive removal (sticky-tape) test is an assessment of somatosensory dysfunction following cerebral ischemia in rats. This test is less time consuming than the original protocol by virtue of requiring minimal pre-training. We present a detailed protocol describing how to conduct the modified adhesive removal (sticky-tape) test. Following right middle cerebral artery occlusion (rMCAo) using an intraluminal filament, animals undergo the modified sticky-tape test (MST) on post-operative days 1, 3, 7 and 10. For the test, a non-removable tape sleeve is placed around the animal's paw and the time to remove the stimulus is measured. The time spent attending to this stimulus is also recorded. Animals undergoing MST for the first time demonstrate nearly-uniform excellent performance. However, following rMCAo, the ratio of left to right performance on the MST is significantly different at all time points. In short, the MST accurately assesses neurological dysfunction in rodents, not only with minimal pre-training, but also with accurate localization to the side of injury.

An improved test of neurological dysfunction following transient focal cerebral ischemia in rats

The Adhesive Removal (sticky-tape) test is a commonly used test of somatosensory dysfunction following cerebral ischemia in rats. This test requires several days of pre-training prior to surgery, which can be time consuming. We present our results with an improved version of the sticky-tape test. Male Wistar rats were subjected to either sham surgery ( n = 4) or right middle cerebral artery occlusion (rMCAo) using an intraluminal filament ( n = 9), followed by a 10-day survival period. On post-operative days (POD) 1, 3, 7, and 10 animals underwent both the conventional sticky-tape test (CST) with measurement of the time to remove the stimulus ( trs), as well as a modified sticky-tape test (MST), in which a non-removable tape sleeve was placed around the animal's paw. Time spent attending to this stimulus ( tas) was recorded. Despite 3 days of pre-training, animals undergoing baseline CST still exhibited marked variability in pre-operative baseline test performance ( trs range 1–60 s). In contrast, animals undergoing MST for the first time demonstrated nearly uniformly excellent performance (% tas range 91.5–98.5% of the 30 s testing period). Although, affected (left) limb performance on both CST (6.8-fold increase in trs on POD 1 compared to baseline) and MST (100% decrease in tas on POD 1 compared to baseline) was markedly altered by rMCAo, CST performance declined bilaterally, and no significant differences in the ratio of affected (left) and unaffected (right) limb performance between sham-operated and rMCAo animals were observed at any time point. In contrast, the ratio of left to right performance on the MST was significantly different at all time points ( P < 0.01). In conclusion, we present a simple modification of the widely used Adhesive Removal test and provide evidence that this test can accurately assess neurological dysfunction in rodents, not only with minimal pre-training, but also with improved localization of the side of injury.

Chaotic components in the high-frequency EEG of rabbit cortex during formation of a conditioned defensive reflex.

The chaotic component of the high-frequency EEG of the rabbit cortex was studied during the development of a conditioned defensive reflex to nonrhythmic light stimulation with electric reinforcement applied to the animal's paw. Regular changes in the dynamic parameters of the chaotic component of the high-frequency EEG were demonstrated. Characteristic changes in the asymptotic evaluations of the correlational dimensionality of the attractor of the chaotic component (DCC) of the high-frequency EEG were detected in the cortical regions studied both during the action of the conditioned stimulus and in background conditions before presentation of combinations. These changes affected both the afferent and efferent cortical regions of the conditioned reflex arc, as well as regions not directly addressed by the conditioned or unconditioned stimuli. These results allow the dynamics of changes in the morphofunctional structures of the conditioned reflex to be seen at the cortical level during learning. Significant differences in the early and late stages of conditioned reflex formation were detected.