Preclinical comparison of antinociceptive effects between ibuprofen, diclofenac, naproxen, and acetaminophen on acid-stimulated body stretching and acid-depressed feeding behaviors in rats.

Pain is a major problem that burdens the health and economy of societies worldwide. Nonsteroidal anti-inflammatory drugs (NSAIDs) are over-the-counter medications that are widely indicated for mild to moderate pain conditions. Clinically, the selection of a medication among this class is mainly based according to both patient's and doctor's previous experiences. Herein, we studied differences in therapeutic efficacies among the most commonly prescribed NSAIDs and acetaminophen in inflammatory pain rat model. Body stretching and food consumption behaviors were assessed after intraperitoneal administration of lactic acid. Initially, different concentrations of lactic acid were evaluated in adult male rats in both behavioral models. Acid concentrations of 1.8 and 3.2% were selected to assess the effects of ibuprofen, diclofenac, naproxen, and acetaminophen in body stretching and feeding behaviors, respectively. In the feeding study, food restriction for 1-24 h prior to feeding studies was assessed at first, and 24 h was selected for further tests. Acetaminophen (100 mg/kg), diclofenac (10 mg/kg), ibuprofen (10-32 mg/kg), and naproxen (3.2-10 mg/kg) significantly decreased acid-stimulated body stretching. Likewise, acetaminophen (100 mg/kg), diclofenac (10 mg/kg), and ibuprofen (32 mg/kg) increased food consumption significantly after 3.2% lactic acid. There were no significant differences between different test drugs efficacies in both stretching and feeding behaviors. In conclusion, feeding behavior provides a good appraisal for pain and analgesic drugs in preclinical studies. There were comparable efficacies between all tested medications in both lactic acid-stimulated body stretching and -depressed feeding behaviors.

Organophosphate pesticide exposure prenatally influence on pregnancy outcomes.

BACKGROUND: Organophosphorus (OP) pesticides are widely used worldwide. The effect of OP exposure during pregnancy on the offspring is inconsistent in the current literature. Moreover, similar studies in the Middle East are lacking. PURPOSE: To examine the effects of OP exposure in utero on the outcome of pregnancies in an agricultural region in Jordan. METHOD: A prospective study, employing a questionnaire to collect women demographic data. Hospital records were collected for newborns' birth data. In addition, urine samples during the third trimester were collected from pregnant women and then analyzed for six OP metabolites to measure exposure. RESULTS: One of the metabolites, DEDTP, was negatively correlated with gestational age and Apgar scores 1 and 5. There were no other significant associations. CONCLUSIONS: Exposure to OP during pregnancy is not highly associated with any negative anthropometric characteristics of the newborns; it is probably offset by other factors.

Evaluation of Vulnerability Factors for Developing Stress and Depression due to COVID-19 Spread and its Associated Lockdown.

Background: COVID-19 is a pandemic that has been widespread throughout the world. The disease and the measures employed to contain its spread have a detrimental effect on the mental health of individuals. Countries across the world have applied variable combinations of quarantine and social distancing measures to contain the spread of COVID-19. This project aims at identifying the susceptible groups for the development of depression and stress due to COVID-19-associated containment measures. This evaluation will help in prioritizing efforts to ameliorate the detrimental effects of COVID-19 on psychological health. Methods: A cross-sectional study was conducted through an online survey that included questions on the demographics and COVID-19 experience. The prevalence of depressive symptoms was evaluated using the PHQ-9 survey, whereas stress levels were detected using the perceived stress scale (PSS). Data regarding demographics as well as exposure to COVID-19, working at home and the financial impact of the pandemic were collected. Results: Data were collected from 1541 participants from the MENA region. Depressive symptoms were detected in 54.2% of the participants, and the average stress score was 18.4±0.8. Adjusting for demographics and other variables, younger participants were more likely to report depressive symptoms and higher stress scores. Additionally, younger age, female gender, the coexistence of depressive symptoms, negative effects on monthly income, and ability to do work were found to be independent predictors of higher stress scores. Conclusion: Young individuals are more likely to develop depression symptoms and stress. Thus, there is a need for prompt measures to alleviate COVID-19-associated effects on this group.

Saccharin and naltrexone prevent increased pain sensitivity and impaired long-term memory induced by repetitive neonatal noxious stimulation: role of BDNF and enkephalin.

This study aim to examine the hypothesis that repetitive painful stimuli during infancy will alter pain sensitivity and impair learning and memory during adulthood and that saccharin will prevent this through its analgesic effect. Naltrexone is used to examine if saccharin effect is mediated via the endogenous opioid system. Pain in rat pups was induced via needle pricks of the paws on day 1 of their birth (P0). All treatments/ manipulations started on day 1 and continued for 2 weeks. The radial arm water maze (RAWM) test was used to assess learning and memory. Pain threshold through foot-withdrawal response to a hot plate was also assessed. At the end of behavioral tests, animals were killed, hippocampus was dissected, and hippocampal levels of ß-endorphin, enkephalin, and brain-derived neurotropic factor (BDNF) were assessed using ELISA. Naltrexone and saccharin combined normalized noxious stimulation induced increased pain sensitivity later in life. Furthermore, naltrexone and saccharin together mitigated the deficiency in learning and memory induced by noxious stimulation. Saccharin treatment prevented reduction in hippocampal enkephalin. Additionally, saccharin prevented hippocampal noxious stimulation induced BDNF decrement. Saccharin prevented long-term memory impairment during adulthood induced by repeated neonatal pain via mechanisms that appear to involve BDNF. Interestingly, naltrexone did not antagonize the effects of saccharin, instead naltrexone augmented saccharin effects.

Management of Sickle Cell Disease Pain among Adolescent and Pediatric Patients.

Management of sickle cell pain in adolescent and pediatric patients is inadequate, and the employment of proper management guidelines and practices are highly variable among different regions and populations. APPT, the multidimensional adolescent pediatric pain tool, promotes optimal pain management and introduces best practical guidelines for pain management. The goal of this study is to assess pain and pain management among young patients diagnosed with sickle cell disease (SCD) by introducing the APPT as a tool for pain management, and analyze factors contributing to pain management. Information relevant to demographic data, SCD characteristics, APPT assessment, and satisfaction of patients regarding pain management were collected using a structured questionnaire. Results showed that SCD is highly associated with gender (p = 0.022), consanguinity (p = 0.012), and number of surgeries (p = 0.013). Most patients (58.9%) indicated the involvement of more than six body areas affected during pain crisis. Severe pain was described by more than half the patients (55.6%), while moderate pain was reported by 31.1%. Most patients described their pain by sensory, affective, and temporal words. The number of painful areas, pain intensity, and use of descriptive pain words was correlated and interpreted by age, BMI, school absence, and number of surgeries. Results of this study could provide guidance to healthcare providers to improve current practices for SCD pain management in order to improve health outcomes and patients' satisfaction.

Early and late anti nociceptive effects of sucrose on neonatal inflammatory pain in rats: Comparison to a non-steroidal anti-inflammatory drug.

Management of neonatal pain is not only ethical but is also essential. Barriers to pain management in infants include lack of safe and effective medications and fear of adverse effects of conventional pain medications. Sweet solutions given intraorally have been shown to reduce pain behaviors and associated symptoms. Sucrose and other sweet solutions are being increasingly used at the NICUs and immunization clinics. Sucrose for mild invasive procedures is effective and safe for those procedures that need to be repeated multiple times during the day. Only few studies examine the efficacy of sucrose for the management of inflammatory pain during infancy. In this study, Complete Freund's Adjuvant (CFA) was used to induce inflammation in 5-day-old rat pups; CFA also produces inflammation that lasts for more than a day, thus can also be a model for chronic pain. Sucrose or ibuprofen was given to subset of pups shortly after CFA intraplantar injections. Thermal as well as mechanical pain sensitivity was assessed on subsequent days as well as during adolescence and early adulthood. Sucrose and ibuprofen were both effective in preventing hyperalgesia and allodynia produced by CFA. Interestingly, sucrose was even more effective than ibuprofen, and the analgesic effects continued further to adolescence and adult life of the rats. Thus, and according to the results of this study, sucrose seems to be just as effective for inflammatory pain as Ibuprofen. In addition, sucrose protects against later-in-life hypersensitivity consequences to neonatal pain.

Prevention of memory impairment induced by post-traumatic stress disorder by cerebrolysin.

Post-traumatic stress disorder (PTSD) may occur after exposure to stressful, fearful or troubling events. Until now, there is no curable medication for this disorder. Cerebrolysin is a neuropeptide, which has an important role in the treatment of vascular dementia. In this study, the probable protective effect of cerebrolysin on PTSD-induced memory impairment was investigated. To induce PTSD, the single prolonged stress (SPS) model was used. Rats were allocated into four groups: control (vehicle-treated), CBL (administrated cerebrolysin 2.5 ml/kg by intraperitoneal route for 4 weeks), SPS (as a model of PTSD and administered vehicle), and CBL-SPS (exposed to SPS and administered cerebrolysin for 4 weeks). Learning and memory were assessed using the radial arm water maze (RAWM). Results showed that SPS impaired both short- and long- term memories; and chronic cerebrolysin administration prevented such effect. Cerebrolysin also prevented decreases in hippocampal GSH levels and GSH/GSSG ratios, and increased GSSG and TBARs, levels induced by PTSD. In conclusion, a protective effect of cerebrolysin administration against SPS model of PTSD induced short- and long- term memory impairment was characterized. This protection could be accomplished, at least partly, by prevention of PTSD induced increase in oxidative stress in the hippocampus via the use of cerebrolysin.

Pharmaceutical care in community pharmacies in Jordan: a public survey.

OBJECTIVE: This study aims to assess the views and attitudes of the general public towards the current role of pharmacists in Jordan. METHODS: This study is a cross-sectional quantitative questionnaire-based study. After a thorough literature review on public perspectives of pharmaceutical care services, a draft questionnaire was designed. This questionnaire was examined and discussed in a focus group of invited public members and was amended accordingly to reach the final draft. The questionnaire was administered using a structured interview technique in which members of the public were asked a series of questions by a trained pharmacist. The study took a place over a period of six months, from January to June 2013. Individuals were recruited from urban and rural areas of Jordan. RESULTS: A total of 1214 respondents were interviewed during the study. Of the respondents, 67.8% were female. Most of the respondent were married (64%) and had a university degree (88.5%). Approximately half of the respondents (55.1%) had no previous knowledge of pharmaceutical care. A relative majority of respondents considered the most important activity performed by pharmacists to be dispensing medications (46.2%), followed by patient counseling (34.6%). The majority of respondents (86.4%) believed that pharmacists have a role in providing healthcare services, and 68% of respondents reported that in order to serve their needs, a pharmacist must consider the patient's needs and engage patients in determining medication timing and options. CONCLUSIONS: The plurality of respondents believed in the importance of pharmacists in providing pharmaceutical care services. However, respondents expected much from pharmacists and felt that their current role was unsatisfying.

Sucrose and naltrexone prevent increased pain sensitivity and impaired long-term memory induced by repetitive neonatal noxious stimulation: Role of BDNF and ß-endorphin.

Pain in neonates is associated with short and long-term adverse outcomes. Data demonstrated that long-term consequences of untreated pain are linked to the plasticity of the neonate's brain. Sucrose is effective and safe for reducing painful procedures from single events. However, the mechanism of sucrose-induced analgesia is not fully understood. The role of the opioid system in this analgesia using the opioid receptor antagonist Naltrexone was investigated, plus the long-term effects on learning and memory formation during adulthood. Pain was induced in rat pups via needle pricks of the paws. Sucrose solution and/or naltrexone were administered before the pricks. All treatments started on day one of birth and continued for two weeks. At the end of 8weeks, behavioral studies were conducted to test spatial learning and memory using radial arm water maze (RAWM), and pain threshold via foot-withdrawal response to a hot plate. The hippocampus was dissected; levels of brain derived neurotrophic factor (BDNF) and endorphins were assessed using ELISA. Acute repetitive neonatal pain increased pain sensitivity later in life, while naltrexone with sucrose decreased pain sensitivity. Naltrexone and/or sucrose prevented neonatal pain induced impairment of long-term memory, while neonatal pain decreased levels of BDNF in the hippocampus; this decrease was averted by sucrose and naltrexone. Sucrose with naltrexone significantly increased ß-endorphin levels in noxiously stimulated rats. In conclusion, naltrexone and sucrose can reverse increased pain sensitivity and impaired long-term memory induced by acute repetitive neonatal pain probably by normalizing BDNF expression and increasing ß-endorphin levels.

Sucrose-induced analgesia during early life modulates adulthood learning and memory formation.

This study is aimed at examining the long-term effects of chronic pain during early life (postnatal day 0 to 8weeks), and intervention using sucrose, on cognitive functions during adulthood in rats. Pain was induced in rat pups via needle pricks of the paws. Sucrose solution or paracetamol was administered for analgesia before the paw prick. Control groups include tactile stimulation to account for handling and touching the paws, and sucrose alone was used. All treatments were started on day one of birth and continued for 8weeks. At the end of the treatments, behavioral studies were conducted to test the spatial learning and memory using radial arm water maze (RAWM), as well as pain threshold via foot-withdrawal response to a hot plate apparatus. Additionally, the hippocampus was dissected, and blood was collected. Levels of neurotrophins (BDNF, IGF-1 and NT-3) and endorphins were assessed using ELISA. The results show that chronic noxious stimulation resulted in comparable foot-withdrawal latency between noxious and tactile groups. On the other hand, pretreatment with sucrose or paracetamol increased pain threshold significantly both in naive rats and noxiously stimulated rats (P<0.05). Chronic pain during early life impaired short-term memory, and sucrose treatment prevented such impairment (P<0.05). Sucrose significantly increased serum levels of endorphin and enkephalin. Chronic pain decreased levels of BDNF in the hippocampus and this decrease was prevented by sucrose and paracetamol treatments. Hippocampal levels of NT-3 and IGF-1 were not affected by any treatment. In conclusion, chronic pain induction during early life induced short memory impairment, and pretreatment with sucrose prevented this impairment via mechanisms that seem to involve BDNF. As evident in the results, sucrose, whether alone or in the presence of pre-noxious stimulation, increases pain threshold in such circumstances; most likely via a mechanism that involves an increase in endogenous opioids.

Sources of information used when prescribing for children, a survey of hospital based pediatricians.

BACKGROUND: Due to the lack of properly tested medicines for children, there is little available information with regards to indications and dosing of medications in children. AIM: To collect data on sources where hospital based pediatricians obtain prescribing information when treating children and the extent of collaboration with the hospital pharmacist. METHOD: Two hundred and fifty pediatricians in different hospitals within different cities in Jordan were asked to fill in a structured questionnaire regarding information sources used when prescribing for children. RESULTS: Questionnaires were collected from 162 (64.8%) hospital based pediatricians, who have completed the questionnaire by the designated date. Most (75.5%) reported that the Lexi Comp's Drug Information Handbook was the source that they most frequently used for drug information when prescribing for in children. The BNF and the BNFc (British National Formulary for children) were found to be the most sources that contain sufficient information that aids pediatricians when prescribing for children. A minority (22%) claimed to consult with the hospital pharmacist when they face difficulties when prescribing for children. CONCLUSIONS: Pediatricians rely on different information sources when they prescribe for children. Those sources vary in their reliability in aiding pediatrician when prescribing. Further work should be done in the provision of useful information on pediatric drug therapy to pediatricians. More steps should be taking place to activate collaboration and interaction between pediatricians and pharmacists as well.