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Open Access Minireview Article

Current Methods Used in the Protein Carbonyl Assay

Nicoleta Carmen Purdel, Denisa Margina, Mihaela Ilie

Annual Research & Review in Biology, Page 2015-2026
DOI: 10.9734/ARRB/2014/8763

Some oxidative stress effects, such as lipid peroxidation or the DNA damage, have been extensively assessed and reliable biomarkers have been associated to characterize the degree of the damage, while the attack of reactive oxygen species on proteins and the formation of protein carbonyls were investigated only in the recent years. Taking into account that protein carbonyls may play an important role in the early diagnosis of pathologies associated with reactive oxygen species overproduction, a robust and reliable method to quantify the protein carbonyls in complex biological samples is also required.
This minireview investigates up-to-date methods used for the separation, identification and quantitative assay of protein carbonyls, a special attention being paid to the advantages and disadvantages of each technique.

Open Access Original Research Article

Measure of Oxidative Stress and Neurotoxicity Biomarkers in Donax trunculus from the Gulf of Annaba (Algeria): Case of the Year 2012

Lamia Bensouda, Nadia Soltani-Mazouni

Annual Research & Review in Biology, Page 1902-1914
DOI: 10.9734/ARRB/2014/7318

Aims: The purpose of our study was to evaluate three biomarkers in an edible species, Donax trunculus (Mollusca, Bivalvia) associated with the environmental pollution in the Annaba gulf. The biomarkers selected were the antioxidant enzyme catalase (CAT), the detoxifying enzyme glutathione S-transferase (GST) and the neurotoxicity marker acetylcholinesterase (AChE).
Place and Duration of Study: Samples were collected monthly in 2012 at two sites in the Annaba gulf (Northeast Algeria): El Battah a relatively clean site and Sidi Salem, a polluted site.
Methodology: Mollusc bivalves (D. trunculus) with the same shell length (25±1mm) were collected monthly from the two sampling sites, transferred to the laboratory and dissected the same day. The mantle was dissected and samples were prepared for biomarker analyses. The enzymes activities were determined by using standard methods.
Results: Biochemical data showed a significant inhibition of AChE activity and a significant increase in both CAT and GST activities in D. trunculus at the site of Sidi Salem compared to El Battah. These changes are discussed in relation to environmental factors and suggested an influence of site quality on the health of D. trunculus.
Conclusion: The measurements of biomarkers in D. trunculus reveals differences between the two sites in relation to their pollution state confirming previous reports. The site of Sidi Salem is more contaminated due to their proximity to different pollution sources. Moreover, the current study gives additional data on the pollution in the gulf of Annaba.

Open Access Original Research Article

Neuroprotective Effect of Dracocephalum moldavica L. Total Flavonoids in Transient Cerebral Ischemia in Rats

Yaxuan Sun, Ting Liu, Xueling Dai, Zhaofen Jiang, Zhaolan Gao, Mei Zhang, Dong Wang, Qiusheng Zheng

Annual Research & Review in Biology, Page 1915-1926
DOI: 10.9734/ARRB/2014/8970

Aims: The aim of the present study was to investigate the potential neuroprotective effects of Dracocephalum moldavica L. total flavonoids (DMTF) on cerebral oxidative stress and damage as well as apoptosis induced by transient cerebral ischemia in rats.
Methodology: Wistar rats were randomly divided into five groups: model group, sham group, DMTF high, middle, low dose groups (50, 25, 12.5 mg/kg). Focal cerebral ischemia/reperfusion was induced by middle cerebral artery occlusion (MCAO) for 2 h, followed by 22 h reperfusion. The reduced glutathione/ oxidized glutathione (GSH/GSSG) ratio, antioxidant enzyme activities, malondialdehyde (MDA), protein carbonyl and 8-hydroxy-deoxyguanosine (8-OHdG) contents were determined. The neuron apoptosis was measured by TdT-mediated dUTP nick end labeling (TUNEL) assay. At last, the neurological deficit was observed.
Results: Transient cerebral ischemia led to significant depress in GSH/GSSG ratio, depletion in antioxidant enzyme activities, rise in MDA, protein carbonyl, 8-OHdG contents, neuron apoptosis and neurological deficit scores. Pre-treatment with DMTF obviously attenuated the brain oxidative stress and damage, apoptosis and neurological deficits.
Conclusion: These findings suggested that DMTF has neuroprotective effect on cerebral ischemia/reperfusion injury which might be related to its antioxidant and anti-apoptosis activity.

Open Access Original Research Article

Statistical Optimization of Culture Media and Conditions for Maximize Production of Mannan by Saccharomyces Cerevisiae Using Response Surface Methodology

Vakilian Aghooi Hanneh, Mortazavi Seyed Ali, Milani Elnaz, Koocheki Arash, Mehraban Masoome

Annual Research & Review in Biology, Page 1927-1940
DOI: 10.9734/ARRB/2014/8712

Aim: In view of the increase in Saccharomyces cerevisiae mannan content, the culture medium and condition for S. cerevisiae were optimized in this study.
Study Design: The mathematical model was established by the quadratic rotary combination design via Response Surface Methodology to evaluate the effect of culture condition and media on mannan content in the yeast cell wall.
Methodology: The influence of culture medium ingredients such as carbon source (FOS, in the range of 2 – 9 g/100ml) and nitrogen source (mixture of peptone and yeast extract, in the range of 1-5g/100ml), and enzyme activator (glycerol, in the range of 1-4g/100ml) on mannan production were evaluated using Response surface methodology. Also The influence of original pH (in the range of 4-7), inoculums size (in the range of 2-4%) and temperature (in the range of 26-32ºC), on mannan production was evaluated and confirmed by quadratic design.
Results: The optimized concentrations of culture medium were determined as follows: 8.99 g/100mL, FOS; 4.25 g/100 ml, mixture of bacto peptone and yeast extract; and 3 g/100mL, glycerol. The order of effect was carbon source› nitrogen source› enzyme activator. Also The order of effect of original pH, inoculums size, and temperature, on mannan production was as follows: temperature > initial pH > inoculation size. The optimized culture condition was pH, 6.62; inoculums size, 4 ml; temperature, 32ºC. The maximum mannan production increased to 94.912 ±9.1 mg/100 ml at the optimum culture condition.
Conclusion: It was evident that the mannan production was affected significantly by culture medium and condition optimization (p < 0.01).

Open Access Original Research Article

Menstrual Disorder: Prevalence and Relation with Sport; A Cross Sectional Study

Zafari Mandana, Aghamohammady Azar, Aliasgharian Aily

Annual Research & Review in Biology, Page 1941-1947
DOI: 10.9734/ARRB/2014/7504

Introduction: The menstrual disorder is very frequent complaint in adolescence age. Our aim of this study is to estimate the prevalence of menstrual disorders in teenage girls and associated with sport.
Method: This cross sectional study was conducted in 8 urban and rural areas in Mazandaran province in north of Iran. One thousands and two hundred teenage girls (14-17 years), 370 girls from rural areas and 690 girls from urban areas entered in our study. Data was collected with questionnaire. We used descriptive statistics, chi- test and in depended T test. Significant level of this study was P<0.05.
Result: The prevalence of menstrual disturbance in urban girls was 13.2% and in rural girls were 8.6%. According to chi- test we can say there is significant relation between menstrual disorder and place of residency (p=0.02). Relation between sport and hypo menorrhea (p=0.191), polymenorhea (p=0.077), metrorrhaghia (p=0.423) were not significant; but the relation between oligomenorhea (p=0.006), amenorrhea (p=0.000) and menorrhagia (p=0.002) were significant.
Conclusion: Menstrual disorder is common in adolescence and regular exercises can reduce some kind of menstrual disorder.

Open Access Original Research Article

Protective Role of Vitamin A against Fetal Injuries Induced by Lipopolysaccharides

Masoud Delashoub, Seyed Mahdi Banan Khojasteh, Ali Khodadadi

Annual Research & Review in Biology, Page 1948-1957
DOI: 10.9734/ARRB/2014/8054

Aim: Lipopolysaccharide (LPS) is One of the important factors that could induce adverse developmental outcome. They include intra-uterine growth retardation (IUGR), intra-uterine fetal death (IUFD) and embryonic resorption and preterm delivery in rodents. That is demonstrated that these are related to oxidative stress induced by LPS. Vitamin A is a fat soluble vitamin that has some antioxidative effects. We investigated protective role of this vitamin against LPS induced fetal defects in rat.
Place and Duration of Study: Department of Basic Science, Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
Between October 2012 and April 2013.
Methodology: First pregnant rats were selected and then were divided to 4 groups. All pregnant rats except controls received an intraperitoneal (75 _g/kg, i.p.) injection of LPS daily on Gestation day (gd) 15–17. The second and third groups received 100 mg kg-1 of vitamin A (I.M.) daily one week before of first injection of LPS. On gd 18, The number of live fetuses, dead fetuses and resorption sites was counted. Live fetuses in each litter were weighted. Crown-rump and tail lengths were examined and skeletal development was evaluated. Also Maternal liver, placenta and fetal liver samples were excised for measurement of TBARS and GSH contents.
Results: Results show administration of LPS significantly increase fetal mortality, decrease fetal weight and crown-rump and tail lengths of live fetuses and retarded skeletal ossification in caudal vertebrae, anterior and posterior phalanges and supraoccipital bone that these are in agreement by other researches.
Conclusion: Our study showed that co-treatment of vitamin A and LPS could decrease defects of LPS and improve injuries. Our study suggests that vitamin A in role of antioxidant could protect fetal injuries induced by LPS in rat.

Open Access Original Research Article

Ceftriaxone Improves Neuron Protection and Functional Recovery in Rat Model of Spinal Cord Injury

Javad Tajkey, Ali Ramazani, Alireza Biglari, Saiedeh mazlomzadeh, Bohlol Habibi Asl

Annual Research & Review in Biology, Page 1958-1967
DOI: 10.9734/ARRB/2014/8308

Aims: To determine the efficacy of ceftriaxone in improvement of neuron protection and functional recovery of spinal cord injury (SCI) in rat model.
Study Design: This study was designed to evaluate the effect of ceftriaxone on neuron protection in rat model of SCI. Rats were randomly divided into four different experimental groups.
Place and Duration of Study: Department of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran, between December 2011 through December 2013.
Methodology: Rats (age, 10 weeks; weight, 165–245 ± 5 g) were randomly divided into four groups of ten (n=40): ceftriaxone before SCI, normal saline before SCI, ceftriaxone after SCI, and normal saline after SCI. SCI was performed on animals under general anesthesia using the weight dropping method. Ceftriaxone was injected intraperitoneally in rats at a dose rate of 200 mg/kg/day for seven days, before and after SCI. Hind limb motor function was assessed using the Basso, Beattie and Bresnahan (BBB) scale. CST axons were traced by injection of biotin dextran amine (BDA), into the sensorimotor cortex.
Result: Our findings showed that ceftriaxone improved functional recovery of SCI in the animal model. Based on the obtained results, there was a statistically significant difference in BBB scores, between groups that received ceftriaxone before and after SCI and control groups. At the same time, significant differences were also observed in axon counting of above mentioned groups.
Conclusion: With attention to increasing demand for innovation of efficient and at the same time cost benefit procedures to improve spinal cord injury, present study seems to be able to open a new way to achieve this goal. No doubt it is still on its experimental model and need further work to validate reliability.

Open Access Original Research Article

Effect of Irrigation and Planting Date on Yield and Water Use Efficiency of Ajowan (Carum copticum)

Hamidreza Nassiri, Mohammadjavad Seghatoleslami, Gholamreza Mousavi, Alireza Ebrahimi

Annual Research & Review in Biology, Page 1968-1979
DOI: 10.9734/ARRB/2014/5928

Aims: This study was conducted to evaluate the effect of irrigation regimes and different planting dates on yield and water use efficiency of ajowan.
Place and Duration of Study: The study was carried out during 2009/2010 and 2010/2011 seasons in Birjand, Iran.
Methodology: Experimental design was split plot based on randomized complete block with three replications. Irrigation intervals (irrigation cut at the beginning of flowering and complete irrigation) as the main factor and six planting dates (December 6, December 21, January 5, February 29, March 30 and April 30) as sub factors.
Results: Results showed that the highest and lowest seed yields and number of seeds per plant was from planting dates of February 29 and March 30, respectively. Results showed that late planting decreased seed yield, number of umbels per plant and number of seeds per plant; but increased number of seeds per umbel and 1000-seed weight. Winter planting had higher yield and biomass water use efficiency compared to spring planting but seed water use efficiency and harvest index were not affected by planting date. The effect of the water stress treatment on plants’ reproductive structures caused decreases to seed yield, seed water use efficiency and seed harvest index.
Conclusion: In general, these showed that winter planting in conditions of drought stress resulted in higher biomass water use efficiency.

Open Access Original Research Article

Photometric Facial Analysis of Soft Tissue Profile of Okrika Adults

E. A. Osunwoke, E. Omin

Annual Research & Review in Biology, Page 1980-1987
DOI: 10.9734/ARRB/2014/5477

Aim: The aim of this study was to determine the facial norms of the Okrika people by photometric analysis.
Study Design: This study is designed to evaluate facial aesthetics and provide photogrammetric standards for male and female Okrika adults.
Place and Duration of Study: The population of study was drawn from natives, who reside within the community centers of Okrika town in Rivers state, south- south, Nigeria between the months of June to December, 2012.
Materials and Method: Standardized photographic records of 245 (comprising 160 males and 85 females) subjects in the natural head position were taken using a digital camera. Measurements taken included; Nasal length, nasal width, nasal tip projection, upper nasal length, lower nasal length and nasofrontal angle. Analysis was done using a software tool for facial analysis and Z-test.
Result: Results showed that the mean of the nasal width was 33.3±0.54mm for males, nasal length 41.8±0.74mm, nasal tip projection 12.2±0.26mm, upper nasal height 31.9±0.56mm, lower nasal height 10.8±0.52mm and Nasofrontal angle 134.13±0.85º while for the females it was 29.9±0.39mm for nasal width, nasal length 38.2±0.49m, nasal tip projection 10.7±0.23mm, upper nasal height 28.0±3.01mm, lower nasal height 10.3±0.19mm, Nasofrontal angle 137.68±5.63º. Significant differences were observed in the parameters measured (P=.05).
Conclusion: This study could be useful in orthodontics and facial plastic surgery.

Open Access Original Research Article

Risk Factors of Mood Disorders (Depression and Anxiety) in Smoking Subjects: Reliability with the Age of Smoking Initiation and Inflammatory Processes

Hacène Frih, Aziez Chettoum, Kamilia Guedri, Nabila Frih, Bachir Rachedi, Rédha Djenidi, Sylvain Fisson

Annual Research & Review in Biology, Page 1988-2006
DOI: 10.9734/ARRB/2014/8040

Aims: The aim of our study was to investigate the causal relationship between smoking and mood disorders (depression, anxiety) and to determine the class at high risk (to developing depression and/or anxiety) depending on age (begin smoking at adulthood (Adt: [23-32] years), childhood (Ch: [5-11] years) or adolescent(Ads: [12-17] years)).
Place and Duration of Study: This study is conducted by Universities of Mentouri Constantine and Badji Mokhtar Annaba, Algeria. Between October 2011 to April 2012.
Methodology: A demographic questionnaire collected data about patient’s characteristics and medical status, the Hospital Anxiety and Depression Scale and Fagerstrom Test. All subjects underwent a thorough medical evaluation and laboratory exam (WBC count, CRP, ESR, Hct). Our study included 96 smokers male divided into several groups according to the desired statistical analysis.
Results: Multivariate analysis by using regression analysis, showed that 85 % of the variability of depression is explained by duration of cigarette smoking (years), the age of smoking initiation (years) and degree of dependence (Fagertstrom). (R (coefficient de corrélation): 0,921; R² (coefficient de détermination): 0,848; DF: 6, F: 82.767, Pr > F: < 0,0001). Therefore, we can conclude with confidence that the three variables do bring a significant amount of information. The correlation is less for anxiety setting (R (coefficient of correlation): 0,759; R² (coefficient of determination): 0,576; DF: 6, F: 20,120, Pr > F: < 0,0001). The relation between depression and inflammatory parameters (CRP, ESR and Htc) was examined using the chi-square test for independence (Χ2-test). This test indicated that depression is clearly related to these inflammatory variables. Furthermore, the ANOVA test indicated that the hematological parameters vary depending the age of smoking initiation.
Conclusion: There is a close relationship between the level of smoking addiction and the emergence of depressive disorders. We suggest an elevated risk of mood disorders in subjects, having a very strong smoking addiction, who began smoking in adulthood and late adolescence versus childhood.

Open Access Original Research Article

Aspects of Fruit Biology of Three Wild Edible Monkey Kola Species Fruits (Cola spp: Malvaceae)

J. U. Ogbu, C. E. Umeokechukwu

Annual Research & Review in Biology, Page 2007-2014
DOI: 10.9734/ARRB/2014/8066

Aims: Monkey kola is a common name given to some edible wild relatives of West African kolanut, viz Cola lateritia K. Schum, C. lepidota K. Schum and C. pachycarpa K. Schum. These are underutilized indigenous tropical fruit species found growing in the humid West and Central African forests. The preliminary study was carried out to examine and characterize the three species of scantly known monkey kola for easy identification and documentation using their fruit morphological features.
Place and Duration of Study: Sample collections from matured ripe fruits of the species were assembled from different locations of southeast Nigeria where these species flourish in the wild and protected stands of home gardens, during the 2011 cropping season.
Methodology: Fruit characters examined for delineation of the species were: shape, fruit size, skin texture and colour; mesocarp colour, that is the edible waxy pulp around the seed, and average number of seeds per species’ fruit. Botanical data of the species were presented after qualitative analysis was made using descriptive statistics.
Results: The species produce botanically identifiable follicle, characteristic of the genus Cola. Of the three, C. parchycarpa showed relatively marked palatable taste as per sweetness of edible fruit part, followed by C. lepidota and C. lateritia in the order. The various species fruits were characterised based on their respective fruit traits for further plant improvement, conservation and domestication purposes.
Conclusion: The present report has attempted presenting basic botanical information about the three edible wild fruits of the Cola spp which were obviously needed for relevant documentation, development of the species descriptors and stimulation of further advance research interest. The results of this study would be useful for conservation and tree improvement programme of the species; however, additional confirmation research is required for other morphological features of the species of agronomic importance.

Open Access Original Research Article

Effect of Some Essential Oils against Rhizoctonia solani and Streptomycetes scabies on Potato Plants in Field Conditions

Serife Evrim Arici, Arif Sanli

Annual Research & Review in Biology, Page 2027-2036
DOI: 10.9734/ARRB/2014/8526

Aim: In this study, efficacy of six essential oils (Cuminum cyminumum, Anethum graveolens, Salvia officinalis, Origanum onites, Rosmarinus officinalis and Lavandula intermedia) in control of Rhizoctonia solani and Streptomycetes scabies on potato plants were tested.
Material and Methods: Essential oil solutions of each species were sprayed uniformly (10 ml for each plant) to aerial parts of potato plants with a manually operated sprayer, when potato plants reached at 15-20 cm height. Controls were sprayed with DMSO (0.5%) and Tween 20 (0.1 %) solutions. Essential oil treatments were repeated 15-day intervals for three times. Plants were harvested in September. Infection of harvested tubers by Rhizoctonia solani and Streptomyces scabies was rated in each plots.
Results: Origanum onites and Anethum graveolens oils reduced disease severity of S. scabies, whereas Lavandula intermedia poorly affected S. scabies. Disease severity of R. solani was 4-4.2% for the Salvia officinalis oil. Disease development was also controlled in the field with the Salvia officinalis oil reducing infection of potato tubers significantly. However, the effectiveness of these essential oils with both the tested pathogens showed different responses.
Conclusion: This study suggests that essential oils have potential as antimicrobial preservatives for the control of Rhizoctonia solani and Streptomycetes scabies on potato plants in filed conditions.

Open Access Original Research Article

Disruption of Cell Wall Fatty Acid Biosynthesis in Mycobacterium tuberculosis Using the Concept of Minimum Robust Domination Energy of Graph

Veeky Baths, Tarkeshwar Singh, Anil Kumar

Annual Research & Review in Biology, Page 2037-2044
DOI: 10.9734/ARRB/2014/8960

Fatty acid biosynthesis of Mycobacterium tuberculosis was analyzed using graph theory and minimum robust domination energy. The digraphs representing this Mycobacterial network provide crucial information regarding the connectivity of each protein or metabolite in a given pathway, providing an important tool into the significance of various components in the pathway, and this can be quantitatively analyzed. Using minimum robust domination energy of the network, the most influential set of proteins which when removed could cause a significant impact on the biosynthetic pathway, were identified. The metabolic network was designed using the KEGG LIGAND database and subjected to graph theory analysis. In the present study minimum robust domination energy of the network was analysed. The minimum robust domination energy of a protein network was used to determine the influence of the said protein on other components in the network. Set of most influential vertices in the network has less robust energy than minimum robust domination energy of the network. Therefore, the most strategic vertices will be the vertices of the influential set which when eliminated will cause maximum disruptions to the metabolic network of this deadly pathogen. This will require lesser energy than the targeted vertices (proteins) of the minimal dominating set.

Open Access Original Research Article

Anti-Cancerous Effect of 4,4'-Dihydroxychalcone ((2E,2'E)-3,3'-(1,4-Phenylene) Bis (1-(4-hydroxyphenyl) Prop-2-en-1-one)) on T47D Breast Cancer Cell Line

Narges Mahmoodi, Tayebeh Besharati-Seidani, Nasrin Motamed, Nosrat O. Mahmoodi

Annual Research & Review in Biology, Page 2045-2052
DOI: 10.9734/ARRB/2014/8484

Aims: The majority of human breast tumors are estrogen receptor α (ERα) positive. However, not all of the ERα+ breast cancers respond to anti-estrogens drugs for those women who do respond, initial positive responses can be of short duration. Thus, more effective drugs are needed to enhance the efficacy of anti-estrogens drugs or to be used separately in a period of time. In view of potential cytotoxicity associated with silybin as polyhydroxy compounds a synthetic 4-hydroxychalcones (bis-phenol) was considered to explore its anti-carcinogenic effects in comparison to silybin on ERα+ breast cancer cell line.
Methodology: We have studied the inhibitory effect of 4,4'-dihydroxychalcone on the T47D breast cancer cell line by MTT test and the IC50s were estimated using Pharm PCS.
Results: The 4,4'-dihydroxychalcone showed significant dose- and time-dependent cell growth inhibitory effects on T47D breast cancer cells. The IC50 of 4,4'-dihydroxychalcone on T47D cells after 24 and 48 hours was 160.88+/-1 µM, 62.20+/-1 µM and for silybin was 373.42+/-1 µM,176.98+/-1 µM respectively.
Conclusion: Our results strongly suggests that this premade synthetic 4,4'-dihydroxychalcone can promote anti carcinogenic actions on T47D cell line. All 4,4'-dihydroxychalcone doses had a much larger inhibitory effect on cell viability than silybin doses in T47D cells. The ratio of the IC50 of 4,4'-dihydroxychalcone to silybin after 24 and 48 hours was 1: 2.3 and 1: 2.8 respectively.

Open Access Review Article

An Overview of Antinociceptive Tolerance to Non-steroidal Anti-inflammatory Drugs

Gulnaz Gurtskaia, Nana Tsiklauri, Ivliane Nozadze, Merab G. Tsagareli

Annual Research & Review in Biology, Page 1887-1901
DOI: 10.9734/ARRB/2014/8001

Purpose of Review: One of the vital functions of the nervous system is to provide information about the threat of injury. The sensation of pain by its inherent aversive nature, contributes to this function. The mainstay of medical pain therapy remains drugs that have been around for decades, like opiates and non-opioid drugs. However, adverse effects of opiates, particularly tolerance, limit their clinical use. Several lines of investigations have shown that systemic administration of non-opioid, non-steroidal anti-inflammatory drugs (NSAIDs) induces antinociception with some effects of tolerance. In this review, we report that repeated microinjections of NSAIDs analgin, clodifen, ketorolac and xefocam into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus in the following 4 days result in progressively less antinociception compared to the saline control testing in the tail-flick reflex and hot plate latency tests. Hence, tolerance develops to these drugs and cross-tolerance to morphine in male rats.
Conclusions: Presented data show that repeated microinjections of NSAIDs into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus induce antinociception and then exhibit tolerance. These findings strongly support the suggestion of endogenous opioid system involvement in NSAIDs antinociception, as it is blocked by an opioid antagonist naloxone. Moreover, the descending pain-control system, the periaqueductal grey – rostral ventro-medial part of medulla circuit should be viewed as a pain-modulation system.