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.

Ultrasound: A novel alternative technique for cervical epidural space visualization-A pilot study.

Background: Neuraxial ultrasound (US), a newer modality, can be used for neuraxial imaging, helping in visualizing and aiding in epidural space catheterization. The aim of this study was to evaluate the efficacy of the US for cervical epidural access and to determine the failure rate and complication associated with this technique. Methods: A prospective single-arm pilot study was conducted on 21 participants. The neuraxial US image quality assessment by Ultrasound Visibility Score (UVS), epidural space depth measurement by US and by conventional loss of resistance (LOR) technique, and post-procedure epidural catheter confirmation by real-time US were the study parameters. Any procedural complications or failure rate were recorded. The Kolmogorov-Smirnov test, paired-samples t-test, and Chi-square test were used for the statistical comparison. Results: The pre-procedural UVS by the transverse interlaminar view (x/21) was 2.81 ± 1.94 and by the oblique paramedian sagittal view was 16.66 ± 2.39 with UVS being best in the paramedian oblique sagittal view (P- value < 0.05). The comparison of depth of the epidural space identified by USG and that by the LOR technique was statistically insignificant (P = 0.83). The average puncture attempts were 1.1 ± 0.3. Post-procedure US epidural catheter confirmation score (x/3) was 1.44 ± 0.44 with either epidural space expansion or microbubbles seen or both. Conclusion: The pilot study has successfully demonstrated the implication of US for visualizing and aiding in epidural space catheterization. Also, the failure rate and procedural complications were drastically minimized with the help of US as compared to the traditional blind technique.

Modulation of the Extracellular Signal-Regulated Protein Kinase and Tissue Inhibitors of Matrix Metalloproteases-1 Gene in Chronic Neuropathic Pain.

OBJECTIVES: The aim of this study is to study the modulation of extracellular signal-regulated protein kinase (ERK) and tissue inhibitors of matrix metalloproteases 1 (TIMP 1) gene in patients with neuropathic pain (NP). MATERIALS AND METHODS: In the present, cross-sectional, observational study, 2 ml of venous baseline sample was withdrawn from all the patients with neuropathic (NP) or non NP (NNP) soon after their diagnosis or on their first visit to the pain clinic. A real-time quantitative polymerase chain reaction experiment was conducted to measure the mRNA expression of TIMP1 and ERK genes in blood samples. The Delta Ct, Delta Ct, and fold change analysis of both the genes were conducted between patients with NP and NNP. RESULTS: A total of 285 patients with chronic pain were assessed, out of which, 153 patients had NP and 132 had NNP. The average duration of chronic pain was 11 months for 285 patients. The mRNA expression of TIMP1 gene is significantly down regulated (2.65-fold) (P (-f. 01), and the mRNA expression level of ERK is significantly up regulated (2.03-fold) (P (-f. 01) in NP patients when compared with NNP. CONCLUSION: The mRNA expression of TIMP1 gene is significantly down regulated, and ERK is significantly up regulated in patients with NP. Further, multicentric trials with larger sample size are recommended to confirm this finding.

Testing Olfactory and Gustatory Dysfunctions among Quarantine COVID-19 Suspects.

The World Health Organization (WHO) has cautioned on specific respiratory symptoms for suspecting an individual of Corona Virus Disease 2019 (COVID-19). Meanwhile, many suspects are reporting dysfunctions of smell and taste. This study aimed to investigate the percentage of positive COVID-19 who had associated loss of sensation as detected by psychophysical testing. Eight hundred and thirty two suspects were enrolled. At the time of sampling for testing COVID-19 status, olfactory dysfunction (OD) and gustatory dysfunction (GD) tested using odorants like coffee and camphor and solutions of sweet and salty solvants, respectively. The strength of the association between test results of these sensory losses and COVID-19 positivity was assessed by calculating sensitivity, specificity, and predictive values. The responses in positive and negative individuals presented as age-adjusted odds ratio with 95% CI. Seventy six (9.1%) [95% CI: 7.4%-11.3%] of 832 suspects were tested positive for COVID-19. Paediatric cases of age between 2 and 10 years could not reply appropriately, hence OD in 134 and GD in 118 could not be tested. Anosmia or hyposmia was present in 62 (81.6%) and ageusia in 64 (84.2%) of the total 76 confirmed cases. The OD and GD dysfunctions were significantly higher among confirmed COVID-19 cases compared to negative subjects [Adj OR (95% CI): Smell 3.22 (1.77-5.88); taste 3.05 (1.61-5.76), p < 0.001]. In this study, testing of smell and taste dysfunctions had higher sensitivity in identifying recent-onset loss of sensations in COVID-19 cases. Hence, it may be used as a simple and cost-effective screening test.