PPARγ and AKt gene modulation following pregabalin and duloxetine combination for painful diabetic polyneuropathy.

Aim: Diabetic peripheral neuropathy (DPN) induces chronic neuropathic pain in diabetic patients. Current treatments like pregabalin and duloxetine offer limited efficacy. This study evaluates combining pregabalin and duloxetine versus pregabalin alone for DPN pain relief, and explores gene modulation (PPARγ and Akt) to understand neuropathic pain's molecular basis.Materials & methods: Diabetic patients with DPN were randomized into groups receiving combination therapy or pregabalin alone for 4 weeks. Pain intensity, gene expression and quality of life were assessed.Results: Combination therapy significantly reduced pain, improved quality of life and upregulated PPARγ and Akt genes compared with monotherapy.Conclusion: Pregabalin and duloxetine combination therapy in DPN led to PPARγ mRNA upregulation and negative correlation of Akt gene expression with pain scores. This combination therapy effectively reduced pain and improved quality of life.Clinical Trial Registration: CTRI/2021/02/031068.

Combining medicines to reduce nerve pain in diabetic patientsWhat is this article about? People with diabetes often have nerve pain called diabetic peripheral neuropathy (DPN). Some medicines like pregabalin and duloxetine help, but are not enough. This study tested if using both medicines together works better than using just pregabalin. The study also looked at how these medicines affect certain genes.What were the results? Patients with DPN took either both medicines or just pregabalin for 4 weeks. The combined treatment reduced pain, improved life quality and affected certain genes.What do the results of the study mean? Using pregabalin and duloxetine together can reduce DPN pain more effectively. This offers hope for better treatment options.

Laparoscopic excision of normotensive variant pheochromocytoma in a case of triple vessel coronary artery disease: The anaesthesia challenge.

Pheochromocytomas are catecholamine-secreting tumours arising mostly from the adrenal medulla. With the advancement in surgical and anaesthetic techniques, the incidence of severe morbidity and mortality associated with surgery is low. However, concurrent coronary artery disease and pheochromocytoma continue to be a challenge due to the risk of adverse cardiovascular events. We describe the successful management of pheochromocytoma excision in a patient with coronary artery disease.

Modulation of mTORC1 and IL-6 following mirror therapy and pregabalin in complex regional pain syndrome type 1.

Aim: The study was designed to evaluate the modulation of mTOR complex 1 (mTORC1) and IL-6 genes following the use of mirror therapy (MT) and pregabalin in complex regional pain syndrome type-1 patients. Materials & methods: Two groups of 20 patients: MT group received MT and pregabalin, control therapy group received pregabalin. Neuropathic pain symptom inventory (NPSI), numeric rating scale - pain, modified motor activity log, SF-12 questionnaire for quality of life and IL-6 and mTORC1 expression were evaluated. Results: Group MT demonstrated a statistically significant improvement in NPSI burning, NPSI allodynia and numeric rating scale pain scores, modified motor activity log and SF-12 scores. Significant downregulation of mTORC1 and IL-6 observed in both. Conclusion: MT is a significant adjunct to pregabalin in improving motor function, quality of life and alleviating pain in complex regional pain syndrome type 1. Clinical Trial Registration: CTRI/2019/01/017272 (ClinicalTrials.gov).

Complex regional pain syndrome is a form of long-term pain that involves an arm or a leg. It can develop after an injury, a surgery or a stroke. Although many drugs have been used for its treatment, the limited relief that these drugs produce along with their side effects have shifted focus to other physical and psychological modes of therapy. Mirror therapy is one such modality where the image of normal functioning limb seen in a mirror placed over the affected limb leads to pain relief in the affected limb. We have provided evidence that mirror therapy can reduce the pain of this syndrome and also decrease the levels of pain related genes in the body. This will help us to devise better treatment strategies for complex regional pain syndrome.

Ultrasound-guided transversalis fascia plane block versus wound infiltration for both acute and chronic post-caesarean pain management - A randomised controlled trial.

Background and Aims: Ultrasound-guided transversalis fascia plane block (USG-guided TFPB) has recently been evaluated for post-caesarean acute pain management. We compared it with standard wound infiltration for both acute and chronic post-caesarean pain management. Methods: All patients undergoing caesarean section (CS) under subarachnoid block were included and randomised. Patients in group C received standard wound infiltration (20 ml of 0.375% ropivacaine) and group-T received bilateral USG-guided TFPB (20 ml of 0.375% ropivacaine) at the end of the surgery. Acute pain assessed using numeric rating scale (NRS), time to first request of analgesia and total rescue analgesic consumption in 24 hours. The incidence of chronic persistent post-surgical pain (CPSP), neuropathic pain component and quality of life (QoL) were assessed. Fisher's exact test, Chi-square test, unpaired Student's t-test and Mann-Whitney U test were used. Results: Sixty patients were included with 30 in each group. NRS score on rest at 6th and 24th hour and on active movement at 1st hour was significantly decreased in group T. The "time to first request of analgesia" was statistically higher in group T, that is, 10.77 ± 1.39 h versus 6.30 ± 1.60 h. Five (16.6%) and two (6.6%) patients in groups C and T, respectively, required rescue analgesia in first 24 hours. 30% (n = 6) and 10% (n = 2) patients in groups C and T, respectively, developed CPSP. The neuropathic pain component was significantly reduced and QoL was significantly improved in group T. Conclusion: TFPB is efficacious for management of both acute and chronic post-caesarean pain management.

Oxytocin infusion rates for maintaining uterine tone during non-elective cesarean section in laboring patients: a randomized, controlled trial.

PURPOSE: Oxytocin infusions for uterine tone maintenance are recommended following initial low oxytocin doses during cesarean section. Very limited literature is available on the optimal infusion rates in laboring patients who have been earlier exposed to oxytocin. METHODS: 105 patients, having received oxytocin for induction/augmentation of labor, received oxytocin infusions at rates of 2.5 IU/h (Group 2.5), 5 IU/h (Group 5) or 10 IU/h (Group 10) following 3 IU slow bolus. The primary outcome measure was estimated intraoperative blood loss; secondary outcome measures included uterine tone adequacy, requirements for additional uterotonics, and any side effects. Minor postpartum hemorrhage (PPH) was defined as blood loss > 500 ml and major/severe hemorrhage as blood loss > 1000 ml. RESULTS: Group 10 had minimum blood loss (311.1 ± 44.9 ml) and uterotonic requirements compared to other groups (p < 0.001). Group 2.5 had maximum blood loss (549.4 ± 74.3 ml) and uterotonic requirements; Group 5 had intermediate values (402.0 ± 49.5 ml). Twenty-six patients in group 2.5 had minor PPH against only one in group 5 and none in group 10 (p < 0.001). No patient in either group had major PPH. The incidence of hypotension was higher in group 10 than in group 2.5 (p = 0.004). Nausea and vomiting were also more frequent in group 10 than in the other two groups. CONCLUSION: Oxytocin infusions at 5 IU/h and 10 IU/h are more effective in reducing blood loss and preventing PPH than 2.5 IU/h. The dose of 10 IU/h, although the most efficacious, is associated with a high incidence of side effects. Hence, further studies are needed to find out the optimal maintenance infusion rate of oxytocin during cesarean section in laboring patients who have received oxytocin earlier.

Modulation of mRNA Expression of IL-6 and mTORC1 and Efficacy and Feasibility of an Integrated Approach Encompassing Cognitive Behavioral Therapy Along with Pregabalin for Management of Neuropathic Pain in Postherpetic Neuralgia: A Pilot Study.

OBJECTIVE: This study was designed to explore the efficacy and feasibility of cognitive behavioral therapy (CBT) along with pregabalin and compare it with pregabalin monotherapy for the management of neuropathic pain in post-herpetic neuralgia (PHN) patients and to explore the modulation of messenger RNA (mRNA) expression of interleukin (IL)-6 and mammalian target of rapamycin-1 (mTORC1) genes in these patients. DESIGN: Randomized controlled pilot study. METHODS: The patients aged >18 years of age with an established diagnosis of PHN with evident allodynia and hyperalgesia who had pain for at least 3 months after healing of rash with pain intensity ≥4/10 on NRS-Pain Scale were enrolled. The trial was registered with the Clinical Trials Registry-India (CTRI/2019/03/018014). A detailed baseline assessment regarding type and duration of pain and disability using pain-relevant self-report questionnaires was done. Two mL venous blood samples were collected for gene expression studies at base line and at end of 12 weeks of treatment. Patients were randomized into one of the two groups. Group PR received pregabalin and Group CP received CBT along with pregabalin. The pain intensity was measured using numeric rating scale (NRS)-Pain scale, neuropathic component of the pain by using Neuropathic Pain Symptom Inventory (NPSI) and Pain Detect Questionnaire (PDQ), sleep interference by NRS-Sleep, pain-related catastrophic thoughts by using Pain Catastrophizing Scale (PCS), depression and quality of life using Beck Depression Inventory-II (BDI-II) and Short Form-12 (SF-12), respectively. The research funding was supported by the intramural grant from the institution. RESULTS: A total of 40 patients with 20 in each group were included. Following integrated approach encompassing CBT and Pregabalin, group CP had significant downregulation of mRNA expression of IL-6; however, no such correlation was observed with mTOR expression. A significant decline in the intensity of pain, NPSI scoring for burning, allodynia, and pain-related catastrophizing were observed; also a significant improvement in depressive symptoms and quality of life were observed with the use of CBT. CONCLUSIONS: A significant downregulation of mRNA expression of IL-6 was observed; however, no significant correlation was observed between NRS pain score and ΔCt values of mRNA expression of both mTORC1 gene and IL-6 gene at baseline and at the end of 12th week. In addition, we note a significant decrease in pain intensity, depressive symptoms, and pain-related catastrophizing while improving QOL was observed with the use of CBT as a clinical adjunct along with pregabalin in PHN patients.

Evaluation of postoperative analgesic efficacy and perioperative hemodynamic changes with low dose intravenous dexmedetomidine infusion in patients undergoing laparoscopic cholecystectomy - A randomised, double-blinded, placebo-controlled trial.

BACKGROUND AND AIM: Dexmedetomidine is a α2-agonist with sedative, sympatholytic and analgesic properties and hence, it can be a very useful adjuvant in anesthesia as stress response buster, sedative and analgesic. We aimed to evaluate the effects of low dose dexmedetomidine infusion (0.5 mcg/kg/h) on postoperative analgesic efficacy along with the perioperative hemodynamic changes in patients undergoing laparoscopic cholecystectomy. MATERIAL AND METHODS: Eighty patients of American Society of Anesthesiologists (ASA) physical grades I and II undergoing laparoscopic cholecystectomy were randomly allocated into two groups of 40 patients each. Group I (Normal Saline group) patients received normal saline and group II (Dexmedetomidine group) patients received dexmedetomidine infusion at 0.5 mcg/kg/h respectively, starting 15 min before induction and continued till the end of surgery. Parameters noted were heart rate, mean arterial pressure, oxygen saturation, post-operative pain was evaluated using VAS and analgesic requirement. Statistical tests such as ANOVA test for continuous variables, post-hoc test for intergroup comparison, and Chi-square test for discrete values were applied. RESULTS: Post-operative efficacy was found to be limited in the dexmedetomidine group in terms of VAS score. The analgesic requirement in 24-hour was observed to be reduced in dexmedetomidine group when compared to the NS group; however, not statistically significant. In group NS, significant hemodynamic stress response was seen following laryngoscopy, tracheal intubation, creation of pneumoperitoneum and extubation. On intergroup comparison, the hemodynamic response was significantly attenuated in the dexmedetomidine group when compared to the NS group. No significant side effects were noted. CONCLUSION: Dexmedetomidine IV in an infusion dose of 0.5 µg/kg/hr is effective in providing postoperative analgesia in terms of significant reduction in analgesic consumption in 24 hours and in addition to the effective obtundation of the pneumoperitoneum-induced hemodynamic changes.

Chronic persistent post-surgical pain following staging laparotomy for carcinoma of ovary and its relationship to signal transduction genes.

BACKGROUND: The present study was undertaken to evaluate the incidence of chronic persistent post-surgical pain (CPPP) and the role of signal transduction genes in patients undergoing staging laparotomy for carcinoma ovary. METHODS: The present observational study was undertaken following institutional ethical committee approval and informed consent from all the participants. A total 21 patients of ASA grade I to III with age 20-70 years, scheduled for elective staging laparotomy for carcinoma ovary were included. Patients were excluded if had other causes of pain, cognitive dysfunction or chronic neurological disorders. Statistical analysis of pool data was done using SPSS version-17. For various scales like GPE, PDQ, NPSI, the visual analogue scale (VAS), global perceived effect (GPE), the pain DETECT questionnaire (PDQ), and neuropathic pain symptoms inventory (NPSI), one factor repaeted measure ANOVA applied with simple contrast with baseline as on post-operative day 1 (considered as reference and compared with subsequent time-interval), and the P values were adjusted according to "Bonferroni adjustments". In patients with CPPP, the Δct values of mRNA expressions of genes at the end of postoperative day 90 were compared with the baseline control values by one factor repeated ANOVA. P value < 0.005 significant. RESULTS: The present study demonstrates 38.1% (8 out of 21 patients) incidence of CPPP. The functional status and quality of life as were observed to be significantly diminished in all patients with chronic pain. An up-regulation in the mRNA expression of signal transduction and a positive correlation was noted between the mRNA expression of signal transduction genes and VAS score in all patients with CPPP at the end of postoperative day 90. CONCLUSIONS: The reported incidence of CPPP in patients with carcinoma ovary was 38.1%. An up-regulation and positive correlation between mRNA expression of signal transduction genes and VAS score depicts its potential role in the pathogenesis of CPPP.