Original Articles

The Optimum Concentration of N-Methyl D-Aspartate to Induce Dorsal Root Ganglion Neuron Activation through the N-Methyl D-Aspartate Receptor Pathway: Creating a Neuron Model For the in-vitro Study of Pain

Ristiawan M Laksono, Handono Kalim, Mohammad S Rohman, Nashi Widodo, Muhammad R Ahmad, Fa’urinda Riam Prabu Nery , Willy Halim

Journal of Cellular & Molecular Anesthesia, Vol. 8 No. 4 (2023), 6 Aban 2023, Page 221-230

Background: In the in-vitro study on chronic pain, the N-methyl D-Aspartate receptor (NMDAR) activation in the dorsal root ganglion (DRG) neuron became one of the most important mechanisms to activate the chronic pain pathways. NMDAR activation can be induced using an NMDAR agonist. No guidelines explain the NMDA optimum concentration to induce DRG neuron activation through the NMDAR pathway. This study aims to find the optimum concentration of NMDA to induce DRG neuron activation through the NMDAR pathway.
Materials and Methods: We treat DRG neuron culture derived from the F11 cell line with 10, 20, 40, 60, 80, and 100 µM NMDA. Phosphorylated extracellular signal-regulated kinase (pERK), an activated neuron biomarker, is measured using an immunocytochemistry assay as a neuron activation biomarker. We validate the NMDA optimum concentration by measuring intracellular Ca2+ level, mitochondrial membrane potential (Δψm), and cytosolic adenosine triphosphate (ATP) in the activated neuron. Those parameters are the downstream process following NMDAR activation and are related to neuron activity. Statistical analysis was performed using the One-Way ANOVA test with α=5%.
Results: We found that NMDA 80 µM significantly had the highest pERK intensity and showed the most optimum neuron activation. Validation tests show an increase in intracellular Ca2+ influx and Δψm. NMDA 80 µM also causes significant depletion in the cytosolic ATP concentration related to neuron activation. NMDA 80 µM induces neuron activation by increasing pERK, Ca2+ influx, Δψm, and cytosolic ATP depletion.
Conclusion: NMDA 80 µM is the optimum concentration to induce DRG neuron activation through the NMDA receptor pathway.

Cognitive Impairments Induced by Repeated Sevoflurane Exposure During Pre-adolescence in Adult Male and Female Rats: Involvement of Biochemical, Histological and Neuroplasticity Approaches

Javad Fahanik Babaei, Maryam Jafarian, Soheila Adeli, Amir Barzegar Behrooz, Seyed Khalil Pestehei

Journal of Cellular & Molecular Anesthesia, Vol. 8 No. 4 (2023), 6 Aban 2023, Page 231-245

Background: In some therapeutic interventions, repeated exposure to pre-adolescence anesthesia is necessary. According to research, exposure to general anesthetics during pre-adolescence can lead to cell death, cognitive and behavioral problems, and neurobehavioral difficulties as an adult. The current study aimed to provide detailed morphological and functional evaluations of the long-term impacts of repeated sevoflurane exposure in male and female rats.
Materials and Methods: Seventy-two pre-adolescent rats were randomly divided into male and female control and inhaled sevoflurane groups (concentration of 2%) daily for 15 days. Animals received care for 20-30 days. The influence of repeated exposure to sevoflurane on cognitive functions was tested using the Morris Water Maze, novel object, and social interaction tests. As a measure of oxidative stress, superoxide dismutase (SOD) and glutathione levels were measured. Toluidine blue stain was utilized to evaluate the number of dark neurons in the hippocampus. Effects of sevoflurane on synaptic plasticity were compared in the performant pathway of the CA1 of the hippocampus.
Results: Repeated sevoflurane exposure in pre-adolescence led to behavioral disorders in male and female adult rats; there was no significant difference in levels of superoxide dismutase and glutathione. We found a significant quantifiable increase in dark neurons. Electrophysiological recordings indicated impaired long-term potentiation and pair-pulse in adult animals that received repeat sevoflurane exposure.
Conclusion: According to our findings, repeated exposure to sevoflurane during pre-adolescence can cause changes in the hippocampus and neuroplasticity in the adult brain. Results from this study may provide a new perspective on how repeated exposure to anesthesia can lead to toxic effects in pre-adolescent rats.

Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomes Can Alleviate the Proctitis Model Through TLR4/NF-Κb Pathway

Zahra Ebrahim Soltani, Mohammad Elahi, Hasti Tashak-Golroudbari, Abolfazl Badripour , Hojjatollah Nazari , Asieh Heirani-Tabasi, Reza Akbari Asbagh , Mohammad Amin Dabbagh Ohadi , Moojan Shabani , Mina Mahboudi , Mojdeh Sarzaeim , Seyed Alireza Mahdavi , Behnam Behboudi , Mohammad Reza Keramati , Alireza Kazemeini , Seyed Mohsen Ahmadi Tafti

Journal of Cellular & Molecular Anesthesia, Vol. 8 No. 4 (2023), 6 Aban 2023, Page 246-255

Background: Proctitis is a significant concern of inflammatory bowel diseases, especially ulcerative colitis. Exosomes are a new method for treating many diseases by their immunosuppressive and tissue-repairing potential. Here, we tried Mesenchymal stem cells (MSCs)-derived Exosomes for treating the proctitis model of rats.
Materials and Methods: Rats were assigned into four groups: sham, control group, rectal, and intraperitoneal exosome injection. The proctitis model was induced by rectal administration of 4% acetic acid. The exosome was derived from human MSCs isolated from human umbilical cords. After seven days, rectum samples were assessed for histopathological, IHC, and PCR analysis.
Results: The histopathologic scores, collagen deposition, and the expression of NF-κB, TLR4, TNFα, IL-6, and TGFβ were decreased in intraperitoneal exosome compared to controls. The result was not promising for the rectal administration of exosomes.
Conclusion: Exosomes can suppress the inflammatory response in the proctitis model and improve the rectum's healing process. Exosomes can inhabit the NF-κB/TLR4 pathway and downstream pro-inflammatory cytokines. This study implicates the therapeutic benefits of exomes in treating proctitis.

Opioid Free Anesthesia in Laparoscopic Surgery: A New Emerging Technique

Carolin Smita Kerketta, Heena Sunil Chhanwal, Divya Kheskani, Vidhyasagar Sharma, Palak Sitapara, Vasu Girdhar Rathod

Journal of Cellular & Molecular Anesthesia, Vol. 8 No. 4 (2023), 6 Aban 2023, Page 256-264

Background: Opioid-free anesthesia (OFA) is a new anesthesiological technique where opioid is avoided intra and post-operative due to side effects. Hence, this study compared opioid-free with opioid-based anesthesia for postoperative analgesia in laparoscopic surgeries. The primary objective was to assess pain scores in the postoperative period with the Numerical rating scale (NRS) for 24 hours, and the secondary objective was to compare intraoperative vitals, postoperative analgesia period, and utilization of total analgesics in the first 24 hours.
Materials and Methods: Prospective randomized control trial, 100 patients aged 20-70 years, American Society of Anaesthesiologists physical class I and II posted for elective upper and lower abdominal laparoscopic surgeries. Patients were divided into two groups (n=50 in each group): opioid-free (Group A) and opioid (Group B). Group A received anesthetic doses of lidocaine, magnesium, and paracetamol in combination with Erector spinae plane block for post-operative pain relief, while group B received intermittent doses of fentanyl. Postoperatively, NRS was observed at 0, 2, 4, and 6 hours during rest and at 0, 2, 4, 6, and 24 hours during movement. Data were analyzed by independent t-test.
Results: Group A showed a significant decrease in NRS score at rest at 0, 2, 4, and 6 hours, whereas there was a significant decrease in NRS score at movement in group A at 0, 2, 6, and 24 hours compared to group B (P< 0.05). Total duration of analgesia (hour) was significantly more in group A (17.86 ± 7.85) as compared to group B (7.76 ± 3.98) (P<0.001). Intraoperative vitals were comparable. The total rescue analgesia (milligram) requirement was significantly low in group A (0.92 ± 0.8) as compared to group B (2.02 ± 0.38).
Conclusion: For patients undergoing elective upper and lower abdominal laparoscopic surgeries, multimodal analgesia was safe in unwanted opioid side-effects cases and unavailability of opioids.

Trans-Nasal Sphenopalatine Ganglion Block Versus Intravenous Aminophylline Injection for Treating Postdural Puncture Headache After Cesarean Section Under Spinal Anesthesia

Tamer Samir Abdelsalam Abdelaziz, Khaled Abdou, Noura Youssri Mahmoud, Ismail Mohammed Ibrahim

Journal of Cellular & Molecular Anesthesia, Vol. 8 No. 4 (2023), 6 Aban 2023, Page 265-273

Background: Postdural puncture headache (PDPH) is a severe and debilitating complication in the obstetric population after regional anesthesia. It affects the parturient and delays home discharge. The epidural blood patch (EBP) is the gold standard treatment; however, it is an invasive and risky procedure. The trans-nasal sphenopalatine ganglion block (SPGB) and intravenous aminophylline are promising modalities for PDPH treatment.
Materials and Methods: In a prospective, double-blinded, and controlled trial, Seventy-five obstetric participants (ASA I and II, aged 18 to 40 years) complaining of PDPH within five days after spinal anesthesia for cesarean section using 22G Quincke needle) were randomized into three groups. Group C received conservative therapy, Group A received intravenous aminophylline plus conservative therapy, and Group S received trans-nasal SPGB plus conservative therapy. Headache severity (VAS score), patient global impression of change (PGIC) scale and the incidence of adverse events were recorded.
Results: Showed that SPGB and intravenous aminophylline significantly reduced the median values of VAS (at 30 minutes,1, 6, 12, and 24 hours) with P≤0.001 and improved 24-hour PGIC with P≤0.001 compared to control. Moreover, SPGB significantly reduced VAS at 30 minutes compared to aminophylline with P=0.004; No significant differences in adverse events.
Conclusion: It is reasonable to offer trans-nasal SPGB, intravenous aminophylline, and conservative therapy as simple, safe, and non-invasive modalities for treating PDPH before EBP.

Background: The preferred anesthetic technique for upper abdominal surgeries, including splenectomy, is general anesthesia (GA). However, these procedures frequently result in severe postoperative pain, necessitating a greater need for efficient pain management. Regional analgesic blocks like the paravertebral block (PVB) and erector spinae plane blocks (ESPB) offer better postoperative pain management.

Materials and Methods Following the induction of GA, 99 patients were randomly assigned to receive bilateral ESPB (n = 33), or bilateral PVB  (n = 33), and a control group (n = 33) received traditional analgesia. Time to 1st  analgesic request was the primary outcome, and total morphine consumption and pain scores over the 1st 24 hours were the secondary outcomes. Postoperative side effects related to the block technique as pneumothorax, or drug side effects, including postoperative nausea and vomiting (PONV), hypotension, bradycardia, pruritus, shivering, and respiratory depression were recorded.

Results Patients in the ESPB  and PVB groups experienced a significantly prolonged time of postoperative analgesia, lower total intra and postoperative opioid consumption, and lower pain scores (NRS) than patients in the control group (P < 0.001). Patients in both ESPB  and PVB   groups showed a significantly lower intraoperative heart rate and mean blood pressure (P < 0.001) after 10 minutes of block. Regarding adverse events,  Pruritus, Shivering, Nausea& vomiting, Urine retention, and Respiratory depression  (P < 0.001) were more frequent in the control group.

Conclusion After an open splenectomy, ultrasound-guided ESPB, and PVB provided comparable postoperative analgesia, reduced the need for overall opioid intake, and lessened the side effects of opioid use. However, ESPB was technically easier.

Keywords Erector spinae plane block; paravertebral block; Bupivacaine; splenectomy


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