Carbamazepine potentiates morphine analgesia on postoperative pain in morphine-dependent rats

Postoperative pain and its control remain one of the most important issues in the field of surgery and health care systems. Morphine is a potent and effective analgesic, but substance abuse patients can manifest crosstolerance to it, making it difficult to satisfy their analgesic/anesthetic requirements. As carbamazepine has shown antinociceptive properties in a variety of experimental and clinical settings, in the present study, we evaluated its potential antiallodynic effects on postoperative pain in naïve and morphine-dependent rats. Male rats were assigned to morphine-dependent and naïve groups and received intraperitoneally drug vehicles as control group, 3 mg/kg morphine, 5, 10 or 15 mg/kg carbamazepine or 5 mg/kg carbamazepine plus 3 mg/kg morphine as a combination therapy 2 and 24 h after surgery. Morphine-dependency was induced with multiple doses of morphine administered i.p. and plantar incision was made on the hind paw to simulate the postoperative pain. Paw withdrawal threshold (PWT) was obtained by von Frey filaments every 30 min after drug injection for up to 180 min. Morphine at 3 mg/kg exerted antiallodynic effects in naïve rats and a decreased antinociception was observed in morphine-dependent rats. In contrast, 5 mg/kg carbamazepine did not significantly alter PWT in naives but it was effective in dependent rats. 10 and 15 mg/kg carbamazepine attenuated allodynia following surgery in both groups. Co-administration of 5 mg/kg carbamazepine with 3 mg/kg morphine produced higher analgesia in morphine-dependent incised rats and prolonged antinociception as compared to morphine alone (Pb0.05). Thus carbamazepine may potentiate the analgesic effect of chronically administered morphine on postoperative pain model in morphinedependent rats

The effectiveness of cognitive-function stress management training in glycemic control in children and in mental health of mother caring for child with type 1 diabetes mellitus

Aim: The study was aimed to evaluate the effectiveness of a training course of cognitive-behavioral stress managementin glycaemia regulation in children with type 1 diabetes mellitus as well as in mental health status of their mothers. Materials and methods: Fifty children with type 1 diabetes mellitus and their mothers were selected and randomly assigned into two groups. A group of mothers (n = 25; as experimental one besides their children) passed a course, eight 2-h sessions, on the cognitive-behavioral and stress management, and the control group received the usual care. To evaluate the effectiveness of the intervention, before and after holding the course, glycosylated hemoglobin (HbA1C) test was done on both groups of children, and also some information was collected from the mothers through interview and the DASS (depression, anxiety, stress scale) and PSI (parenting stress index) questionnaires. Results: After the intervention, HbA1c level decreased in the experimental group. Feeling of depression, anxiety and stress was significantly lower than the control group. Furthermore, training for parenting stress management positively affected on the sense of demanding, reinforcement, and adaptability in child domain and also on attachment, competence, depression, relationship with spouse and family health in parent domain. Conclusion: The intervention program was significantly effective in reducing the amount of HbA1c in diabetic children, and also reduced the intensity of psychosocial problems such as depression, anxiety and stress in the mothers caring for children with type 1 diabetes

Anti-allodynic Effect of Nefopam and Morphine in a Rat Model of Neuropathic Pain

Please cite this article as: Moini Zanjani T, Saghaei E, Ameli H, Sabetkasaei M. Anti-allodynic Effect of Nefopam and Morphine in a Rat Model of Neuropathic Pain. Novel Biomed 2013;1:16-22.Background: Neuropathic pain is a chronic pain due to a disorder in the peripheral or central nervous system with different pathophysiological mechanisms. Current treatments are not effective. Here we compared the analgesic effect of nefopam, and morphine in chronic constriction injury (CCI) model of neuropathic pain.Methods: Male wistar rat (150-200g, n=8) were divided into 3 different groups: 1- Saline-treated CCI group, 2- Saline-treated sham group, and 3- Drug-treated CCI groups. In CCI model of neuropathic pain, the left sciatic nerve was exposed and 4 loose chromic gut ligatures were placed around the nerve proximal to the trifurcation. Ketamine 60mg/kg and xylazine 10 mg/kg were used for anesthesia. Nefopam (10, 20, 30mg/kg), and morphine (1, 3, 5mg/kg) were injected 30 minutes before surgery and continued daily to day 14 post-ligation. Von Frey filaments for mechanical allodynia and acetone test for cold allodynia were respectively used as pain behavioral tests. Experiments were performed on day 0 (before surgery) and days 1, 3, 5,7,10 and 14 post injury. Behavioral studies were performed in a quiet room between 9:00 to 11:00 AM. All experiments followed the IASP guidelines on ethical standards for investigation of experimental pain in animals.Results: Nefopam (20 and 30mg/kg) blocked mechanical and cold allodynia during the experimental period, but the analgesic effects of morphine (5mg/kg) lasted for 7 days.Conclusions: It seems that nefopam could effectively reduce pain behavior compared to morphine with reduced adverse effects

Effects of Zizyphus jujube Extract on Memory and Learning Impairment Induced by Bilateral Electric Lesions of the Nucleus Basalis of Meynert in Rat

Alzheimer's disease (AD) is a common neurodegenerative condition that affects the elderly population. Its primary symptom is memory loss. The memory dysfunction in AD has been associated with cortical cholinergic deficiency and loss of cholinergic neurons of the nucleus basalis of Meynert (NBM). Zizyphus jujube (ZJ) activates choline acetyltransferase and may have beneficial effects in AD patients. This study investigates the effect of ZJ extract in intact rats and in rat model of AD. 49 male Wistar rats were divided into seven equal groups (1-control, without surgery, received water), 2-AD (bilateral NBM lesion, received water), 3 and 4-AD + ZJ (NBM bilateral lesion, received ZJ extract 500 and 1,000 mg/kg b.w. per day for 15 days), 5-sham (surgery: electrode introduced into NBM without lesion, received water), 6 and 7-without surgery and lesion, received ZJ extract-the same as groups 3 and 4). The learning and memory performance were assessed using passive avoidance paradigm, and the memory cognition for spatial learning and memory was evaluated by Morris water maze. In shuttle box test ZJ extract (500 and 1,000 mg) significantly increased step-through latency in AD + ZJ groups compared with AD group. In Morris water maze test (in probe day), both AD + ZJ groups receiving extract (500 and 1,000 mg) demonstrated significant preference for the quadrant in which the platform was located on the preceding day as compared with AD group. Our results suggested that ZJ has repairing effects on memory and behavioral disorders produced by NBM lesion in rats and may have beneficial effects in treatment of AD patients

Progesterone exerts antidepressant-like effect in a mouse model of maternal separation stress through mitigation of neuroinflammatory response and oxidative stress

Context: Experiencing early-life adversity plays a key role in the development of mood disorders in adulthood. Experiencing adversities during early life period negatively affects brain development. Sex steroids such as progesterone affect the brain structure and functions and subsequently affects behaviour. Objective: We assess the antidepressant-like effect of progesterone in a mouse model of maternal separation (MS) stress, focussing on its anti-neuroinflammatory and antioxidative effects. Materials and methods: NMRI mice were treated with progesterone (10, 50, and 100 mg/kg, i.p., respectively) for 14 days. Valid behavioural tests including forced swimming test (FST), splash test and open field test (OFT) were used. Quantitative reverse transcription-PCR (qRT-PCR) was used for evaluation of genetic expression in the hippocampus. Antioxidant capacity was assessed by the FRAP method and the level of malondialdehide by TBA. Results: MS provoked depressive-like behaviour in mice. Treatment of MS mice with progesterone increased the grooming activity time in the splash test and decreased the immobility time in the FST. In addition, progesterone decreased the expression of inflammatory genes related to neuroinflammation (IL-1 beta, TNF-alpha, TLR4 and NLRP3) as well as increased the antioxidant capacity and decreased the lipid peroxidation (MDA) in the hippocampus. Discussion and Conclusion: Administration of progesterone significantly mitigated the negative effects of MS on behaviours relevant to depressive-like behaviour as well as attenuated neuro-immune response and oxidative stress in the hippocampus of MS mice. In this context, we conclude that progesterone, at least partially, via attenuation of oxidative stress and neuroinflammation, exerts antidepressant-like effects

The demyelination and altered motor performance following electrolytic lesion in the ventrolateral white matter of spinal cord in male rats: Benefit of post-injury administration of estradiol

Introduction: Spinal cord injuries are accompanied with significant demyelination of axons and subsequent locomotor dysfunction. To identify the extent of damage following electrolytic lesion of ventrolateral white matter, essential area for initiation of locomotor activity, we assessed demyelination as well as alteration in motor performance. Moreover, the protective effect of estradiol as a candidate treatment for preservation of myelin and locomotor activity after injury was examined due to its antiapoptotic and anti-inflammatory activities. Methods: A unilateral electrolytic lesion positioned in the right ventrolateral funiculus (VLF) was applied following laminectomy at T8-T9. In the estradiol-treated injury group, animals received a pharmacological single dose of estradiol valerate (4 mg/kg) at 30min post injury. Locomotor function was assessed using rotarod and open field tasks during 4 weeks after injury. Results: Obtained results showed significant demyelination at the site of injury and caudal areas following lesion as well as altered motor performance. Post-spinal cord injury administration of estradiol enhanced white matter maintenance at the site of lesion, restored the level of myelin basic protein (MBP), decreased TUNEL positive cells and improved functional recovery. Conclusion: Taken together, these results indicate that demyelination after lesion in VLF may be a contributing factor to limited motor performance, and suggest that pharmacological doses of estradiol may have an early protective effect through sparing of white matter. © 2016, Iranian Society of Physiology and Pharmacology. All rights reserved

Integration of substance use disorders program in general medicine education program based on Kern model

Background: Substance Use Disorders (SUD) are one of the biggest public health problems nationally and globally. It is necessary to provide specific educating programs about SUDs. The purpose of this study was to integrate some trainings which are related to substance use disorders in general medicine education.Methods: This study was a quasi-experimental and pre-test post-test intervention research. Participants were 114 students studying at different stages of medical education at Shahrekord University of Medical Sciences. The training program was designed based on the training model of David Kern. Training was integrated into pharmacology, psychology, poisoning and forensic medicine courses.  The present researchers organized a life skill workshop for third-semester medical students. The students visited an addiction treatment exhibition during community medicine externship as well. Assessment tools included questionnaires to assess knowledge, attitude, and satisfaction. Data were analyzed by SPSS 18 software.Result: In all interventions, the mean score of knowledge and knowledge self-assessment increased significantly after the intervention (p<0.001). Students' attitudes about the curriculum were favorable. Satisfaction of the majority of students about the program was high. The highest level of satisfaction was related to the internship addiction emergency program.Conclusion: The positive effect of all interventions on the perception, attitude, and satisfaction of medical students emphasized that modifying the medical educational curriculum through considering the pattern, content, and results of the interventions can be very effective in improving the performance of physicians in the field of addiction management

Diosmetin Mitigates Cognitive and Memory Impairment Provoked by Chronic Unpredictable Mild Stress in Mice

Background and Aim. Numerous reports have indicated that dealing with stressors in life is a main risk factor for the occurrence and progression of cognitive and memory impairment. Available treatments such as benzodiazepine and antidepressants address only certain aspects of this stress disorder and have numerous side effects. The present study was aimed at investigating the effect of diosmetin, as a flavonoid compound with potent antioxidant and anti-inflammatory effects, on cognitive impairment and chronic stress memory. Materials and Methods. In the present experimental study, male NMRI mice were exposed to chronic unpredictable mild stress (CUMS) paradigm for 35 days. Diosmetin (at doses of 10, 20, and 40 mg/kg. i.p.) or diosmetin solvent (normal saline + DMSO, 1 ml/kg; i.p.) was administered 30 min before stress induction. After 28 days, memory and cognitive performance were assessed by shuttle box and novel object recognition tests. Finally, antioxidant capacity (FRAP) and malondialdehyde (MDA) level of serum and brain, and serum corticosterone level were evaluated. Results. Behavioral tests showed that CUMS significantly reduced the secondary latency in passive avoidance memory test and diagnosis index in novel object recognition test compared to the control group (P<0.001), whereas treatment with diosmetin (20 and 40 mg/kg) significantly improved memory performance in the two tests (P<0.001). In addition, diosmetin (40 mg/kg) could pronouncedly suppress increase in serum corticosterone levels, reduction in antioxidant capacity, and production of excess MDA caused by CUMS compared to the control group (P<0.01, P<0.001, and P<0.001, respectively). Conclusion. Chronic stress can impair memory and cognition and treatment with diosmetin can partly improve this disorder in male mice by increasing the antioxidant capacity of brain tissue and serum and improving serum corticosterone levels

Role of Microglia and Astrocyte in Central Pain Syndrome Following Electrolytic Lesion at the Spinothalamic Tract in Rats

Central pain syndrome (CPS) is a debilitating state and one of the consequences of spinal cord injury in patients. Many pathophysiological aspects of CPS are not well documented. Spinal glia activation has been identified as a key factor in the sensory component of chronic pain. In this study, the role of glial subtypes in the process of CPS induced by unilateral electrolytic lesion of spinothalamic tract (STT) is investigated. Male rats received a laminectomy at T8–T9 and then unilateral electrolytic lesion centered on the STT. Thermal and mechanical thresholds as well as locomotor function were measured on days 0, 3, 7, 14, 21, and 28 post-injuries by tail flick, von Frey filament, and open field tests, respectively. To investigate the spinal glial activation following denervation in STT-lesioned groups, Iba1 and GFAP were detected by immunohistochemistry and Western blotting at the same time points. Data showed that STT lesion significantly decreased thermal pain at day 3 in comparison with sham groups. Significant bilateral allodynia appeared in hind paws at day 14 after spinal cord injury and continued to day 28 (P<0.05). Additionally, electrolytic spinal lesion attenuated locomotor function of injured animals after 7 days (P<0.05). In both histological assessments and Western blotting, Iba1 increased at days 3 and 7 while increased GFAP occurred from day 14 to 28 after lesion. It appears that microglial activation is important in the early stages of pain development and astrocytic activation occurs later. These events may lead to behavioral outcomes especially central neuropathic pain

Estradiol attenuates spinal cord injury-induced pain by suppressing microglial activation in thalamic VPL nuclei of rats.

In our previous study we showed that central pain syndrome (CPS) induced by electrolytic injury caused in the unilateral spinothalamic tract (STT) is a concomitant of glial alteration at the site of injury. Here, we investigated the activity of glial cells in thalamic ventral posterolateral nuclei (VPL) and their contribution to CPS. We also examined whether post-injury administration of a pharmacological dose of estradiol can attenuate CPS and associated molecular changes. Based on the results,in the ipsilateral VPL the microglial phenotype switched o hyperactive mode and Iba1 expression was increased significantly on days 21 and 28 post-injury. The same feature was observed in contralateral VPL on day 28 (P<.05). These changes were strongly correlated with the onset of CPS (r(2)=0.670). STT injury did not induce significant astroglial response in both ipsilateral and contralateral VPL. Estradiol attenuated bilateral mechanical hypersensitivity 14 days after STT lesion (P<.05). Estradiol also suppressed microglial activation in the VPL. Taken together, these findings indicate that selective STT lesion induces bilateral microglia activation in VPL which might contribute to mechanical hypersensitivity. Furthermore, a pharmacological dose of estradiol reduces central pain possibly via suppression of glial activity in VPL region