Newly discovered functions of miRNAs in neuropathic pain: Transitioning from recent discoveries to innovative underlying mechanisms.

Neuropathic pain is a widespread clinical issue caused by somatosensory nervous system damage, affecting numerous individuals. It poses considerable economic and public health challenges, and managing it can be challenging due to unclear underlying mechanisms. Nevertheless, emerging evidence suggests that neurogenic inflammation and neuroinflammation play a role in developing pain patterns. Emerging evidence suggests that neurogenic inflammation and neuroinflammation play significant roles in developing neuropathic pain within the nervous system. Increased/decreased miRNA expression patterns could affect the progression of neuropathic and inflammatory pain by controlling nerve regeneration, neuroinflammation, and the expression of abnormal ion channels. However, our limited knowledge of miRNA targets hinders a complete grasp of miRNA's functions. Meanwhile, exploring exosomal miRNA, a recently uncovered role, has significantly advanced our comprehension of neuropathic pain's pathophysiology in recent times. In this review, we present a comprehensive overview of the latest miRNA studies and explore the possible ways miRNAs might play a role in the development of neuropathic pain.

S1 Transforaminal Epidural Anesthesia in Percutaneous Transforaminal Endoscopic Discectomy: A Case-Series Study.

Background: Percutaneous transforaminal endoscopic discectomy (PTED) has become popular over the years due to its safety and low invasiveness. This surgery can be performed with different anesthesia techniques; however, the extent to which the surgeon and patient are satisfied with the analgesia is debatable. Objectives: This study investigated the efficiency of the S1 transforaminal epidural block. Methods: This retrospective study was conducted on 60 patients with L4 - L5 lumbar disc herniation who underwent PTED under the S1 transforaminal epidural block. All patients had clinical symptoms associated with unilateral radiculopathy and were candidates for surgery. Percutaneous transforaminal endoscopy and S1 epidural block were performed by a surgeon for all patients. Results: Of the 60 evaluated cases, 61.7% and 38.3% were female and male, respectively, with a mean age of 42.98 ± 10.79 years. The mean pain score before surgery was 7.83 ± 0.69, which decreased to 2.58 ± 0.65 during surgery and 0.50 ± 0.50 48 hours after surgery (P < 0.001). The mean duration of operation in these patients was 58.58 ± 16.95 minutes, and the mean onset time was 10.08 ± 3.12 minutes. Moreover, the mean bleeding was 124.17 ± 25.20 cc. Conclusions: The PTED with S1 epidural anesthesia is a simple, safe, and effective method that causes good analgesia during the operation and cooperates well with the surgeon in neurological monitoring due to patient consciousness.

Efficacy, safety, and tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Breakthrough pain (BTP) is an important challenge in treatment and requires a rapid onset of action for pain control. BTP should be adequately controlled with a stable dose of a short-acting oral opioid. So far, no drug is available for the treatment of BTP in cancer patients in Iran, so we designed the first study in Iran to investigate the effect of sublingual fentanyl in relief of pain episodes in these patients. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of sublingual fentanyl in the treatment of breakthrough pain in cancer patients. METHOD: This study was a randomized double-blind placebo-controlled clinical trial in cancer patients with breakthrough pain (at least 1-4 episodes of acute pain with moderate to severe pain daily) referred to the pain clinic of Akhtar and Masih Daneshvari hospitals in 2019. The study consisted of two stages: 100 patients were selected by simple, non-random sampling and entered the open-label titration phase. The primary efficacy endpoint was the sum of pain intensity difference over 30 min post-administration. Secondary efficacy endpoints included pain intensity difference (PID) and pain relief (PR) throughout the 60-min post-dose assessment period. In the double-blind study, patients were randomly divided into two groups of placebo (n=50) and intervention (sublingual fentanyl tablet) (n=50). For evaluation of efficacy, 10 episodes were treated in each group and the results were recorded by the patient. (Clinical trial registration: IRCT20131124015515N8). RESULTS: A total of 100 patients entered the titration phase, primary efficacy of sublingual fentanyl was 3.5±0.6 and secondary efficacy of sublingual fentanyl (60 min, after treatment) was 0.3±0.6 which was statistically significant. In the titration phase, the treatment success rate was 100%. In the double-blind phase of the study, the pain intensity in multiple episodes showed a significant improvement at 15, 30, 45, and 60 min after drug administration (P=0.0001). The intensity of pain in each episode was significantly decreased compared to the next episode (P=0.0001). The mean frequency of pain episodes in the sublingual fentanyl group showed a significant decrease (P=0.0001). The most common adverse drug events in the titration phase were drowsiness (20%), dizziness (7%), and nausea 4%, and in the double-blind phase only drowsiness (12%). (Cancer Research Center, Shahid Beheshti University of Medical Sciences, Survey). CONCLUSION: Sublingual fentanyl appears to be effective for patients with rapid-onset analgesia, has short-acting duration, is effective medication, safe, and well tolerated. It is a suitable choice in Iranian patients with chronic cancer-related pain controlled suffering from acute pain episodes related to cancer.

Effects of luteolin and luteolin-morphine co-administration on acute and chronic pain and sciatic nerve ligated-induced neuropathy in mice.

Background Neuropathic pain (NP) is a common condition accompanied by nerve injury. To date, there is no definite treatment approved for this disorder. In addition, many drugs that are used for NP cause adverse reactions. Luteolin is a naturally occurring flavonoid with diverse pharmacological properties such as anti-inflammatory, antioxidant and anticancer. We sought to investigate luteolin effects on chronic, acute and neuropathic pain as well as its potential to increase morphine anti-nociceptive effects in mice. Methods Albino mice (20-25 g) were randomly divided into 14 groups (n=7) including morphine 1 mg/kg body weight +luteolin (5 mg/kg body weight), morphine (9 mg/kg body weight, i.p.), luteolin (2.5, 5 and 10 mg/kg body weight), imipramine 40 mg/kg body weight and normal saline (NS) (0.9 %) as vehicle and subjected to hot plate test. Formalin test was done in the following groups: NS, diclofenac sodium (10 mg/kg body weight, i.p.), morphine (9 mg/kg body weight, i.p.) and luteolin (2.5, 5 and 10 mg/kg body weight). Results Administration of luteolin single dose (5 and 10 mg/kg body weight) significantly reduced neuropathic pain ( p<0.05$\rm{p}<0.05$) in comparison to negative control. Anti-nociceptive effects of luteolin were comparable to imipramine as the standard positive control ( p<0.001$\rm{p}<0.001$). Co-administration of luteolin and morphine potentiated morphine 1 mg/kg body weight painkilling effects ( p<0.001$\rm{p}<0.001$). Conclusions Our results showed that luteolin alone reduces neuropathic pain. Furthermore, when co-administered with morphine 1 mg/kg body weight, luteolin potentiates morphine effects. Therefore, luteolin-morphine co-administration might be a valuable alternative for the conventional treatment.

Moderate hypothermia and its effects in reducing the applied dose of anesthetics for patients with opium dependence in cardiac surgery: A randomized controlled trial.

BACKGROUND: An increasing number of patients addicted to opium are experiencing awareness during coronary artery bypass surgery (CABG) as a result of tolerance to anesthetics. OBJECTIVES: This research was primarily intended to determine the potential diminishing effects of moderate hypothermia on anesthetic dosage and recall of anesthesia during the procedure. METHODS: In this double-blind randomized controlled trial, a total of 80 CABG candidates with known addiction to opium were divided into two groups: one normothermic (N) and the other moderately hypothermic (H), both undergoing induction as well as close monitoring from September 2014 to January 2016. The candidates were initially set for a target bispectral index (BIS) score of between 40 and 60. As the score rose to 60, an additional dose of propofol was administered, alongside rise in blood pressure and tear-shedding. To enhance the accuracy of our evaluation of anesthetic depth, we also used two questionnaires to test candidates' recall filled with the assistance of a colleague 24 hours following surgery. Independent-samples t-test and chi-square test were used by SPSS v 18 for data analysis. RESULTS: Eighty patients were studied in two groups of normothermic (N) (n = 40) and hypothermic (H) (n = 40). Given similar demographic data as well as the duration of surgery, we arrived at a propofol dose of 122.52±13.11 cc for normothermic patients and 101.28±14.06 cc for hypothermic subjects (p=0.001). As for fentanyl, the total required sum came up to 39.60±21.04 cc and 31.72±5.81 cc for the above-mentioned groups in order (p=0.025). Moreover, the post-operative interview showed that there was no report of a patient with memory recall following surgery. CONCLUSIONS: Moderate hypothermia can substantially reduce the need for anesthetics in patients with addiction to opium when undergoing CABG surgery. TRIAL REGISTRATION: This study is registered in Iranian Registry of Clinical Trials with registration number of IRCT2014050513159N5. FUNDING: This research was supported financially by the Research Council of Mashhad University of Medical Sciences (grant number 920405).

Correlation of Wnt and NOTCH pathways in esophageal squamous cell carcinoma.

There is an inevitable association between cell signaling pathways and tumorigenesis. Wnt and notch pathways play important roles during development and self-renewal. Beside the independent role of such pathways on tumor progression, different cross talks between these pathways through tumorigenesis are emphasized. In this study, we analyzed cross talk between Wnt and NOTCH signaling pathways through assessment of probable correlation between MAML1 and PYGO2 as the main transcription factors of these pathways, respectively in esophageal squamous cell carcinoma (ESCC) patients. Levels of MAML1 and PYGO2 mRNA expression in 48 ESCC patients were compared to the correlated margin normal tissues using real-time polymerase chain reaction (PCR). Eleven out of 48 patients (22.9 %) have shown the concomitant MAML1/PYGO2 over expression in significant correlation with tumor size (p = 0.046) and depth of tumor invasion (p = 0.050). We showed that there is a significant correlation and feedback between these markers during the ESCC progression and metastasis.

Role of Msi1 and PYGO2 in esophageal squamous cell carcinoma depth of invasion.

Deregulation of developmental signaling pathways such as Wnt/b-catenin and NOTCH are commonly observed in different cancers. A normal wnt pathway is essential for development and tissue homeostasis to preserve a normal balance between the differentiation and proliferation. PYGO2 is the main transcription factor of wnt pathway, while Msi1 is one of the wnt inhibitors. In this study we assessed the correlation between Msi1 and PYGO2 mRNA expression using Real time polymerase chain reaction in 48 esophageal squamous cell carcinoma (ESCC) patients. Although, there was not any significant correlation between the levels of Msi1 and PYGO2 mRNA expression, we observed a significant correlation between the Msi1 and PYGO2 overexpressed cases and depth of tumor invasion (p = 0.05). In conclusion, despite the role of these markers in tumor depth of invasion there is not any feedback between Msi1 and PYGO2 gene expression in ESCC.

The Effectiveness of Group Assertiveness Training on Happiness in Rural Adolescent Females With Substance Abusing Parents.

BACKGROUND: Parental substance abuse confronts children with a variety of psychological, social, and behavioral problems. Children of substance abusing parents show higher levels of psychiatric disorders including anxiety and depression and exert lower levels of communication skills. Weak social skills in this group of adolescents put them at a higher risk for substance abuse. Many studies showed school based interventions such as life skill training can effective on future substance abusing in these high risk adolescences. MATERIALS AND METHODS: The participants consisted of 57 middles schools girls, all living in rural areas and having both parents with substance dependency. The participants were randomly assigned to intervention (n=28) and control (n=29) groups. The data were collected before and six weeks after training in both group. The intervention group received eight sessions of group assertiveness training. Participants were compared in terms of changes in scores on the Oxford Happiness Questionnaire and the Gambrills-Richey Assertion Inventory. RESULTS: The total score for happiness change from 43.68 ±17.62 to 51.57 ±16.35 and assertiveness score changed from 110.33±16.05 to 90.40±12.84. There was a significant difference in pretest-posttest change in scores for intervention (7.89±4.13) and control (-2.51±2.64) groups; t (55) =2.15, p = 0.049. These results suggest that intervention really does have an effect on happiness and assertiveness. CONCLUSION: Determining the effectiveness of these school based interventions on other life aspects such as substance abuse calls for further study on these rural adolescent girls.

Personality Traits and Identity Styles in Methamphetamine-Dependent Women: A Comparative Study.

BACKGROUND: Studies over the past two decades have shown that various personality traits of substance-dependent men measure differently than compared to normal individuals. However fewer studies have addressed the role of identity as an influential factor in the onset and continuation of drug dependency. METHODS: The objective of this study was to compare the Big Five personality factors and identity styles in methamphetamine dependent women and non-user group. Forty eight methamphetamine dependent women under treatment in Welfare Organization's residential centers filled out the NEO Five-Factor Inventory (NEO-FFI) and the Berzonsky's Identity Style Inventory. They were compared with 48 non-dependent women who were matched in terms of age, education, marital status, and occupation. Data was analyzed with t student test. Statistical analyses were performed using the SPSS V.16 software. Differences were considered significant at P<0.05. RESULTS: Results found that methamphetamine dependent woman had significantly higher levels of neuroticism and lower levels of conscientiousness, agreeableness and openness to experience compared to normative sample of female respondents .In addition, mean scores of diffuse/avoidant identity style in methamphetamine user women was significantly higher than non-user group. This is while non-user women had a significantly higher mean in normative identity style. CONCLUSION: Identity styles along with personality traits can be a key role in drug use in women in this study. Therefore, enhancing understanding about the role of identity can be helpful in treatment programs especially in harm reduction approaches.

Role of Msi1 and MAML1 in Regulation of Notch Signaling Pathway in Patients with Esophageal Squamous Cell Carcinoma.

PURPOSE: Developmental pathways such as Wnt and Notch are involved in different cellular functions from the cell cycle regulation to self-renewal. Therefore, aberrations in these pathways may cause tumorigenesis. Msi1 has a critical regulatory role for the Wnt and Notch pathways. In the present study, we have assessed the probable correlation between the Msi1 and MAML1 in esophageal squamous cell carcinoma (ESCC) progression and metastasis. METHODS: Levels of Msi1 and MAML1 mRNA expression in 51 ESCC patients were compared to the normal tissues using real-time polymerase chain reaction (PCR). RESULTS: Nine out of 51 (17.6 %) cases had Msi1/MAML1 overexpression, and there was a significant correlation between such overexpressed cases and tumor location (p = 0.013). CONCLUSIONS: We showed that there is not any direct correlation and feedback between the Msi1 and MAML1 in ESCC patients.

Survival after judicial hanging.

Hanging is known not only as a common method of suicide but also as a capital punishment method in some countries. Although several cases have been reported to survive after the attempted suicidal/accidental hanging, to the extent of our knowledge, no modern case of survival after judicial hanging exists. We reported a case of an individual who revived after modern judicial hanging despite being declared dead. The case was admitted with poor clinical presentations and the Glasgow Coma Scale of 6/15. The victim received all the standard supportive intensive care and gained complete clinical recovery.

The optimization of essential oils supercritical CO2 extraction from Lavandula hybrida through static-dynamic steps procedure and semi-continuous technique using response surface method.

AIM: The aim of this study was to examine and evaluate crucial variables in essential oils extraction process from Lavandula hybrida through static-dynamic and semi-continuous techniques using response surface method. MATERIALS AND METHODS: Essential oil components were extracted from Lavandula hybrida (Lavandin) flowers using supercritical carbon dioxide via static-dynamic steps (SDS) procedure, and semi-continuous (SC) technique. RESULTS: Using response surface method the optimum extraction yield (4.768%) was obtained via SDS at 108.7 bar, 48.5°C, 120 min (static: 8×15), 24 min (dynamic: 8×3 min) in contrast to the 4.620% extraction yield for the SC at 111.6 bar, 49.2°C, 14 min (static), 121.1 min (dynamic). CONCLUSION: The results indicated that a substantial reduction (81.56%) solvent usage (kg CO2/g oil) is observed in the SDS method versus the conventional SC method.

Right Atrium Myxoma After Lung Adenocarcinoma.

INTRODUCTION: Heart secondary tumors are much more common than primary tumors. These two types of tumors differ not only by their source but also by their symptoms and location in heart chambers. CASE PRESENTATION: This report presents a 66-year-old heavy smoker female with a history of pulmonary lobectomy due to lung adenocarcinoma, hysterectomy due to myoma, and lumpectomy due to benign breast mass, who had symptoms of right heart failure for months. Physical examinations followed by imaging showed a mass in her right atrium, which was most likely, a myxoma. After a successful surgical excision, histopathological findings confirmed the diagnosis. More studies are needed to evaluate a possible combination between these soft tissue masses. CONCLUSIONS: A right atrium myxoma in a patient with a history of multiple soft tissue tumors has been limited to only a few cases. This may suggest a genomic affinity or similarity; if so, those with multiple different type soft tissue masses should be screened for a heart mass before the mass becomes complicated.

Effect of ginger (Zingiber officinale) on heavy menstrual bleeding: a placebo-controlled, randomized clinical trial.

OBJECTIVE: A wide range of herbal plants have been reported to treat various gynecological problems of women. This study was set out to investigate the effect of ginger (Zingiber officinale) on heavy menstrual bleeding (HMB) in high school girls. METHODS: Ninety-two young women who experienced HMB and met the inclusion criteria were recruited in this study. Participants were evaluated for six consecutive menstrual cycles. During 3 assessment cycles, their HMB was confirmed by Pictorial Blood Assessment Chart. They were then randomly allocated to two study groups to receive either ginger or placebo capsules. The participants filled in the same chart during three intervention cycles. RESULTS: The level of menstrual blood loss dramatically declined during the three intervention cycles in ginger-receiving group. The decrease of blood loss in ginger-receiving group was significantly more remarkable than that of participants receiving placebo (p<0.001). Minimum number of participants reported adverse effects. CONCLUSION: HMB is highly prevalent among young women. Considering the significance of appropriate and timely treatment and also the importance of prevention of unwanted consequences, ginger may be considered as an effective therapeutic option for HMB.