<i>PPARγ</i> and <i>AKt</i> gene modulation following pregabalin and duloxetine combination for painful diabetic polyneuropathy
Creators: name: Saxena, Ashok K
name: Thanikkal, Nimisha
name: Chilkoti, Geetanjali T
name: Gondode, Prakash G
name: Sharma, Tusha
name: Banerjee, Basu D
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Science Policy
subject: Mental Health
subject: Infectious Diseases
subject: FOS: Health sciences

description: <b>Aim:</b> 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 (<i>PPARγ</i> and <i>Akt</i>) to understand neuropathic pain's molecular basis. <b>Materials &amp; methods:</b> 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. <b>Results:</b> Combination therapy significantly reduced pain, improved quality of life and upregulated <i>PPARγ</i> and <i>Akt</i> genes compared with monotherapy. <b>Conclusion:</b> Pregabalin and duloxetine combination therapy in DPN led to <i>PPARγ</i> mRNA upregulation and negative correlation of <i>Akt</i> gene expression with pain scores. This combination therapy effectively reduced pain and improved quality of life. <b>Clinical Trial Registration:</b> CTRI/2021/02/031068. <b>Combining medicines to reduce nerve pain in diabetic patients</b> 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. 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. Using pregabalin and duloxetine together can reduce DPN pain more effectively. This offers hope for better treatment options. First comparative study: This research pioneers a comparison between pregabalin and duloxetine combination therapy and pregabalin monotherapy in painful diabetic peripheral neuropathy (DPN), offering crucial insights into advanced treatment methods. Gene modulation exploration: The study innovatively explores mRNA expression modulation in <i>PPARγ</i> and <i>Akt</i> genes post 4 weeks of drug therapy in DPN patients, illuminating molecular responses and deepening our understanding. Positive pain relief outcomes: Notable reductions in Numerical rating scale (NRS)-pain scores were observed with the combination therapy group displaying superior efficacy compared with monotherapy, emphasizing its effectiveness in pain management. Improved quality of life: The research highlighted enhancements in various aspects of patients' lives, including reduced neuropathic symptoms, improved sleep, and higher SF-12 questionnaire scores, signifying a comprehensive positive impact. Clinical Implications: A large-scale randomized controlled trial is warranted to validate the findings of the present study emphasizing upon the future prospect of personalized gene-targeted therapies for patients with Diabetic peripheral neuropathy (DPN). The significant upregulation of the <i>PPARγ</i> gene suggests prolonged analgesic efficacy, paving the way for innovative neuropathic pain management approaches.