Paroxetine effects on morphine analgesic tolerance in rats.

OBJECTIVES: To alleviate different pain intensities, morphine administration has been extensively used. However, prolonged administration of morphine leads to a progressive decline of its analgesic effect which limits their overall utility. Morphine tolerance is considered as a challenging issue for the treatment of both acute and chronic pain. We conducted this study in rats to investigate the effect of paroxetine on morphine tolerance when used preemptively or after morphine tolerance had developed. METHODS: Male Wistar rats (weight 250-300 g, n=10) were used to evaluate the effects of paroxetine on tolerance to morphine. In order to induce tolerance, daily intraperitoneal injection of morphine (7 mg/kg) was done. After tolerance induction, a group of animals received intraperitoneal injection of 10 mg/kg paroxetine 30 min prior to each morphine dose. In another trial, to investigate the potential of paroxetine to prevent tolerance to morphine, animals were pretreated with 10 mg/kg paroxetine 30 min before morphine administration. In the control groups, 10 mL/kg of saline was injected. The behavioral test (tail-flick test) was done for all groups. RESULTS: Our data showed that paroxetine significantly reversed tolerance to morphine when used after tolerance induction (p<0.001). However, administration of paroxetine before occurrence of tolerance had no effect. CONCLUSIONS: We conclude that paroxetine could decrease tolerance to morphine when used after the occurrence of morphine tolerance, while it was not able to prevent morphine tolerance when administered preemptively. ETHICAL COMMITTEE NUMBER: IRIB.SBMU.MSP.REC.1394.098.

The effect of microglial inhibition on the expression of BDNF, KCC2, and GABAA receptor before and after the establishment of CCI-induced neuropathic pain model.

Damage to the peripheral or central nervous system results in neuropathic pain. Based on a complicated mechanism, neuropathic pain has no efficient treatment so far. It has been well-known that the expression of some proteins (BDNF, KCC2, GABA-A) during neuropathic pain changes. Microglial cell activation is considered as a trigger to alter the expression of these proteins. In the current study, the effect of minocycline as a potent microglial activation inhibitor on the gene and protein expression of these neuropathic pain mediators was investigated. This experiment was done in two paradigms, preinjury and postinjury administration of minocycline. In each paradigm, male Wistar rats (weight 150-200 g, n = 6) were allocated to sham, control, and drug groups. Minocycline (30 mg/kg, i.p.) was injected 1 h before or at day seven after nerve injury and continued till day 14 in the preemptive or postinjury part of the study, respectively. After the last injection, the animals were decapitated and the lumbar part of the spinal cord was isolated to assess the expression of genes and proteins of interest. In the preventive study, minocycline increased the expression of KCC2 and GABA-A/γ2 proteins and decreased BDNF expression. On the other hand, the target gene expression and protein expression were not changed when minocycline was administered after nerve injury. It seems that minocycline was able to change the expression of proteins of interest merely when used before nerve damage.

Purinergic receptor ligands: the cytokine storm attenuators, potential therapeutic agents for the treatment of COVID-19.

The coronavirus disease-19 (COVID-19), at first, was reported in Wuhan, China, and then rapidly became pandemic throughout the world. Cytokine storm syndrome (CSS) in COVID-19 patients is associated with high levels of cytokines and chemokines that cause multiple organ failure, systemic inflammation, and hemodynamic instabilities. Acute respiratory distress syndrome (ARDS), a common complication of COVID-19, is a consequence of cytokine storm. In this regard, several drugs have been being investigated to suppress this inflammatory condition. Purinergic signaling receptors comprising of P1 adenosine and P2 purinoceptors play a critical role in inflammation. Therefore, activation or inhibition of some subtypes of these kinds of receptors is most likely to be beneficial to attenuate cytokine storm. This article summarizes suggested therapeutic drugs with potential anti-inflammatory effects through purinergic receptors.

Evaluation of neurosonology versus digital subtraction angiography in acute stroke patients.

Stroke is one of the most common neurological disorders with a high incidence in Middle-eastern regions. We aimed to assess the diagnostic accuracy of neurovascular ultrasound to detect of cerebral artery stenosis compared to digital subtraction angiography (DSA) as a gold standard method. Eighty patients presenting with symptoms of cerebral ischemia were enrolled in the study. They were examined by cervical color Doppler ultrasound and TCCS to determine stenosis of extracranial and intracranial arteries, respectively. DSA was performed 24-48 h after the initial examination. The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of neurovascular ultrasound in comparison to DSA were calculated. The agreement between the two methods was determined by kappa statistics. Eighty patients (60% male, 40% female) with a mean age of 61.32 ± 12.6 years were included. In 65% of patients, stenosis in carotid artery caused ischemic symptoms. We did not observe any stenosis in anterior cerebral artery, posterior cerebral artery and basilar artery in patients. The agreement between the neurovascular ultrasound and DSA in various arterial vessels was 0.9 for common carotid artery, 0.86 for internal carotid artery, 0.78 for middle cerebral artery, and 0.86 for vertebral artery. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and kappa value of the neurovascular ultrasound for detecting stenosis regarding the arterial segments were 84.8%, 81%, 92.6%, 65.4%, 83.8, and 0.71, respectively. In conclusion, the neurovascular ultrasound is a valuable, non-invasive, and repeatable method to investigate cerebral artery stenosis with high diagnostic accuracy.

Evaluation of reliability and validity of the Persian version of the Neurological Disorders Depression Inventory for Epilepsy (P-NDDI-E).

INTRODUCTION: Major depression is common among people with epilepsy (PWE), but it is underdiagnosed. The aim of the present study was to assess the reliability and validity of the Persian version of the Neurological Disorders Depression Inventory for Epilepsy (P-NDDI-E) as a screening tool for major depression in patients with epilepsy. METHOD: A total of 210 patients suffering from epilepsy have been assessed using the NDDI-E and the Beck Depression Inventory-II (BDI-II) with no difficulty in understanding or answering the Persian version of the questionnaire. Patients identified as depressed under BDI-II underwent a psychiatric evaluation to confirm depression according to 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) criteria. RESULT: According to the BDI-II and the ICD-10 criteria, major depression was diagnosed in 75 patients (32% men, 68% women). Cronbach's α coefficient was 0.826, suggesting a very good internal consistency. The receiver operating characteristic analysis showed an area under the curve of 0.90 (95% confidence interval [CI] = 0.86-0.94, standard error [SE]: 0.02, p < 0.001). A cutoff of ≥14 resulted in an 83% sensitivity, an 80% specificity, a 70.1% positive predictive value, and an 88.6% negative predictive value. A significant and positive correlation between the P-NDDI-E and the BDI-II was shown (Spearman's ρ = 0.604, p < 0.001). DISCUSSION: The P-NDDI-E could be used as a reliable and valid instrument in detecting major depression in PWE.