G. Mostafa

Inhibition of brain oxidative stress and inducible nitric oxide synthase expression by thymoquinone attenuates the development of morphine tolerance and dependence in mice

In this study, the effect of thymoquinone on morphine-induced tolerance and dependence in mice was investigated. Repeated administration of thymoquinone along with morphine attenuated the development of morphine tolerance, as measured by the hot plate test, and dependence, as assessed by naloxone-precipitated withdrawal manifestations. Concurrently, morphine-induced progressive increase in brain malondialdehyde (MDA) level and nitric oxide (NO) production as well as progressive decrease in brain intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity were inhibited by co-administration of thymoquinone. Morphine-induced progressive increase in brain glutamate level was not inhibited by concomitant administration of thymoquinone. Similarly, co-administration of thymoquinone inhibited naloxone-induced increase in brain MDA level, NO overproduction and decrease in brain intracellular GSH level and GSH-Px activities but it did not inhibit naloxone-induced elevation of brain glutamate level in morphine-dependent mice. The inhibitory effect of thymoquinone on morphine-induced tolerance and dependence on naloxone-induced biochemical alterations in morphine-dependent mice was enhanced by concurrent i.p. administration of the NMDA receptor antagonist, dizocilpine, the antioxidant, N-acetylcysteine or the NO synthase inhibitor, L-N (G)-nitroarginine methyl ester. On the other hand, this inhibitory effect of thymoquinone was antagonized by concurrent i.p. administration of NO precursor, L-arginine. In addition, concomitant administration of thymoquinone inhibited morphine tolerance and dependence-induced increase in inducible but not in neuronal NO synthase mRNA expression in mice brain. These results demonstrate that inhibition of morphine-induced oxidative stress, increase in the expression of brain inducible NO synthase and NO overproduction by thymoquinone can attenuate the development of morphine tolerance and dependence.

Role of oxidative stress and inducible nitric oxide synthase in morphine-induced tolerance and dependence in mice. Effect of alpha-lipoic acid

In this study, the possible role of oxidative stress and nitric oxide (NO) synthase isoforms in the development of morphine tolerance and dependence, and effect of alpha-lipoic acid on these parameters were investigated in mice. The development of morphine tolerance as measured by the hot plate test and dependence, as assessed by naloxone-precipitated withdrawal manifestations, produced an increase in brain glutamate and malondialdehyde (MDA) levels and NO production as well as a decrease in brain intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity. Also, the development of these syndromes increased inducible but not neuronal NO synthase mRNA and protein expressions in mice brain. Co-administration of alpha-lipoic acid (α-LA) inhibited the development of morphine tolerance and dependence, their associated biochemical alterations, except elevation of brain glutamate level, and their associated increase in brain inducible NO synthase mRNA and protein expressions. The inhibitory effect of α-LA on morphine-induced tolerance and dependence and on naloxone-induced biochemical alterations in morphine-dependent mice was enhanced by concurrent administration of the NMDA receptor antagonist, dizocilpine, the antioxidant, N-acetylcysteine or the selective inducible NO synthase inhibitor, aminoguanidine. On the other hand, this inhibitory effect of α-LA was not changed by concurrent administration of the selective neuronal NO synthase inhibitor, 7-nitroindazole but antagonized by concurrent administration of the NO precursor, L-arginine. These results suggest that α-LA through inhibition of morphine-induced oxidative stress and increase in the expression and activity of inducible NO synthase in the brain can attenuate the development of morphine tolerance and dependence.

Repetitive transcranial magnetic stimulation in neuropathic pain secondary to malignancy: A randomized clinical trial

Significant analgesic effects of repetitive transcranial magnetic stimulation (rTMS) have been found in several studies of patients with chronic pain of various origins, but never for malignancy. The objective of this study was to assess the efficacy of 10 sessions of rTMS over the primary motor cortex (M1) in patients suffering from malignant neuropathic pain.

Comparative evaluation of the effect of tricyclic antidepressants on inducible nitric oxide synthase expression in neuropathic pain model

The analgesic effect of acute i.p. administration of amitriptyline (norepinepherine and serotonin reuptake inhibitor), clomipramine (serotonin reuptake inhibitor) and desipramine (norepinepherine reuptake inhibitor) was studied in chronic constriction injury (CCI) model of sciatic nerve in rats and mRNA and protein expression of inducible nitric oxide synthase (iNOS) were also investigated. Acute treatment with amitriptyline and clomipramine produced antinociceptive effects after sciatic nerve injury and blockade of norepinephrine reuptake using desipramine did not demonstrate antinociceptive effects. The antinociceptive effect of amitriptyline, not clomipramine, was augmented by the selective iNOS inhibitor, aminoguanidine. Amitriptyline inhibited iNOS mRNA and protein expression in cerebellum and hippocampus. However, desipramine altered neither iNOS expression at mRNA level nor at post-transcriptional level. Based on our experimental findings, we conclude that the analgesic effect of the dual norepinepherine and serotonin reuptake inhibitor, amitriptyline, is partially due to inhibition of central iNOS.

Premedication with intranasal dexmedetomidine, midazolam and ketamine for children undergoing bone marrow biopsy and aspirate

Abstract Background Preanesthetic medication in pediatrics is very helpful in relieving anxiety, fear, and psychological trauma due to maternal deprivation. Many drugs used in different routes aiming to alleviate stress and prevent psychological trauma. Of these drugs midazolam and ketamine are commonly used. We aimed in this work to compare both of them with dexmedetomidine which is α 2-agonist when used intranasally in children undergoing bone marrow biopsy and aspirate in sedation and premedication. Methods 96 children aged 2–8 years with ASA physical status II scheduled for bone marrow biopsy and aspirate were divided into three groups 32 child in each one: (M group) who were premedicated with intranasal midazolam 0.2 mg/kg, (D group) who were premedicated with intranasal dexmedetomidine 1 μg/kg, and (K group) who were premedicated with intranasal ketamine 5 mg/kg. The degree of sedation was assessed every 5 min for 30 min by using a 4 point sedation scale. Also, child–parent separation was assessed and graded according to a 4 point scale at 30 min. Results We found that dexmedetomidine group achieved a faster sedation score less than 3 at the point of 10 min, then all groups achieved a comparable sedation score till point of 25 min, both dexmedetomidine and midazolam groups had better sedation score than ketamine group at 30 min. Children achieved child–parents separation score grade 1 was significantly higher in dexmedetomidine group than midazolam and ketamine groups. Conclusions Midazolam, ketamine and dexmedetomidine produced adequate sedation with little side effects. So, we prefer to use midazolam due its efficacy and safety as well as availability and its low price in comparison to ketamine and dexmedetomidine.

Therapeutic effects of peripheral magnetic stimulation on traumatic brachial plexopathy: clinical and neurophysiological study.

OBJECTIVE To evaluate the therapeutic effects of peripheral repetitive magnetic stimulation (rMS) on recovery of traumatic brachial plexopathy. PATIENTS AND METHODS Thirty-four patients with traumatic brachial plexopathy were studied. Strength of different muscles of upper limbs was evaluated neurologically. Nerve conduction studies (NCS), upper limb F-waves and visual analogue scales (VAS) for shoulder pain were obtained for all patients. These were randomly assigned into two groups with a ratio of 2:1; each patient received conventional physical therapy modalities and active exercises as well as real or sham rMS applied over the superior trapezius muscle of the affected limb daily for 10 sessions. Patients were reassessed with the same parameters after the 5th and the 10th session, and 1 month after rMS treatment. RESULTS No significant between-group differences were recorded at baseline assessment. Significant improvement was observed (time X groups) after real rMS in comparison to the sham group (P=0.0001 for muscle strength and 0.01 for VAS of shoulder pain). These improvements were still present at 1 month after the end of treatment. In accordance with the clinical improvement, a significant improvement was recorded in the neurophysiological parameters in the real vs the sham group. CONCLUSIONS We demonstrate that peripheral rMS for 10 sessions may have positive therapeutic effects on motor recovery and pain relief in patients with traumatic brachial plexopathy. Therefore, it is a useful adjuvant in the therapy of these patients.

Ketamine versus magnesium sulfate with caudal bupivacaine block in pediatric inguinoscrotal surgery: A prospective randomized observer-blinded study

Introduction: Possible approaches for postoperative analgesia after pediatric inguinoscrotal surgery are caudal block by bupivacaine/ketamine (BK) and bupivacaine/magnesium sulfate (BM). Aim: The purpose of the following study is to compare the analgesic efficacy and safety of ketamine and magnesium sulfate in combination with bupivacaine for caudal blockade in pediatric patients after inguinoscrotal operations. Materials and Methods: Patients randomly received one of the two solutions for caudal epidural injection after induction of general anesthesia. Group-BK: Were given a mixture of 0.25% bupivacaine and 0.5 mg/kg of ketamine. Group-BM: Were given a mixture of 0.25% bupivacaine and 50 mg magnesium sulfate. Postoperatively, a blinded post-anesthesia care unit nurse assessed the quality of analgesia with a visual pain analog scale (VPAS). Significant pain is defined as one that has a VAPS of ≥3. Results: Forty American Society of Anesthesiologists I-II children (20 in each group) completed the study. The two groups were comparable regards age, sex, body mass index, anesthesia and surgery durations, recovery time and sevoflurane concentration. The mean duration of caudal analgesia ± standard deviation was 462 ± 17.2 min versus 398.05 ± 12.9 min for BK and BM groups, receptively (P < 0.001). Supplemental rectal paracetamol within 12 h postoperatively were 15% for BK group versus 25% for BM (P = 0.05). Four patients in BK group only experienced postoperative nausea and vomiting (P = 0.053). Conclusion: Caudal administration of BK is efficient and safe for pediatric inguinoscrotal operations with longer postoperative analgesia than BM sulfate.