Background & Aims
Background:
Diabetic Peripheral Neuropathy (DPN) is a distressing complication frequently encountered worldwide in approximately 50% of diabetics. Patients with DPN experience sharp shooting pain, often stabbing & tingling in nature and at times associated with diabetic foot and autonomic involvement. Various modalities used for pain management in DPN include tricyclics, pregabalin, gabapentin, duloxetine, venlafaxine, lidocaine, topical agents, and epalrestat etc. This study explores the analgesic efficacy of combination pharmacotherapy of pregabalin and duloxetine versus pregabalin monotherapy and modulation of mRNA expression of PPAR-Gamma & Akt genes in patients of painful DPN.
In this study the data obtained was analysed statistically using SPSS version 20.0, utilizing Mann-whitney test, Wilcoxon Signed Rank test, Independent t-test, Chi-square test, & Spearman Rank Correlation (Spearman`s Rho).
Methods
Methodology:
Following institutional ethical committee clearance & written informed consent, this randomized, double-blind study recruited thirty patients, M/F, ?18 yrs, with DPN for at least 3 months with score ?3 on Michigan Neuropathy screening, with NRS pain ?4/10, & brief pain inventory-MSF (BPI-MSF) ?4/10, & with stable glycemic control. Patients in study group C received fixed- dose combination of pregabalin and duloxetine for total of 4 weeks and patients in control group M received pregabalin monotherapy for a total of 4 weeks. All patients were assessed for NRS-pain scores, BPI-MSF scores, PDQ scores, NRS-sleep scores, NPSI scores & SF-12 questionnaire scores, in addition to rescue analgesia & side-effect records, at the end of 1st, 2nd and 4th week. The mRNA expressions of PPAR-Gamma and Akt genes in blood were evaluated at baseline and at the end of 4th week follow-up. Estimation of mRNA expression of PPAR-Gamma & Akt genes were done by using Real-time PCR in three steps.
Results
Results:
Our findings reveal that in 2 grps. with comparable demographic profile, prim. outcome measures (NRS score and NPSI score) & sec. outcome measures (BPI-MSF score, PDQ score, NRS-sleep score, SF-12 score) showed significant(p<0.05) improvement on intragroup comparisons in study grp. C and grp. M. On intergroup comparisons, there was significant (p<0.05) improvement in NRS-Pain score, BPI-MSF score, & NPSI score in burning & tingling at end of 2nd wk of treatment in study grp. C as compared to grp. M. However NRS-sleep score, PDQ score & SF-12 QOL score, improved significantly(p<0.05) at end of 4th wk in study group C compared to group M. mRNA expression of PPAR-Gamma and Akt genes were significantly(p<0.05) upregulated in both groups as compared to baseline.On Intergroup comparisons, upregulation of mRNA expression of PPAR-Gamma and not Akt gene, was observed to be significantly(p<0.05) more upregulated in the study grp C as compared to grp M, at end of 4th wk of treatment
Conclusions
Conclusion:
This study suggests significant( p<0.05) pain relief and improvement in QOL, following pregabalin plus duloxetine combination therapy, as compared to pregabalin monotherapy in patients of DPN. The mRNA expression of PPAR-gamma was observed to be significantly ( p<0.05) more upregulated following utilization of combination pharmacotherapy of pregabalin and duloxetine as compared to pregabalin monotherapy, and it indicates longer lasting analgesic efficacy of this combination, possibly due to significant ( p<0.05) modulation of PPAR-Gamma gene, which is essentially involved in insulin metabolism pathway. There is an urgent need to undertake larger prospective, multicentric RCTs to validate our clinical findings & to substantiate our findings of mRNA expressions of PPAR-Gamma gene and Akt gene following combination pharmacotherapy in patients of DPN.
References
1. Saxena AK, Nath S, Kapoor R. Diabetic Peripheral Neuropathy: Current Concepts and Future Perspectives. J Endocrinaol Diab 2015;2(5):1-18
2. Saxena AK, jain P, Dureja GP et al. Pharmacological management of neuropathic pain in india: A consensus statement from Indian experts. Indian J Pain. 2018;32(3): 132-144.
3. ko YC, Lee CH, Wu CS et al. Comparison of efficacy and safety of gabapentin and duloxetine in painful diabetic peripheral neuropathy: A systemic review and meta-analysis of randomised controlled trials. Int J Clin Pract. 2021;75(11):e14576.
4. Happich M, Schneider E, Boess FG et al. Effectiveness of Duloxetine Compared with pregabalin and gabapentin in Diabetic Peripheral Neuropathic Pain Results from a German Observational Study. Clin J Pain 2014;30:875-885.
5. Goldstein DJ, Lu Y, Detke MJ et al. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain. 2005;116(1-2):109-18.
6. Shahid W, Kumar R, Shaikh A et al. Comparison of the efficacy of duloxetine and pregabalin in pain relief associated with diabetic neuropathy. Cureus.2019;11(7):e5293.
7. Radhakrishnan C, Anjusha UT, Sreejith K et al. Safety and efficacy of pregabalin treatment and quality of life in patients treated with pregabalin in painful diabetic peripheral neuropathy . Diabetes. 2018;67.
8. Roy MK, Kuriakose AS, Varma Sk et al. A study on comparative efficacy and cost effectiveness of pregabalin and duloxetine used in diabetic neuropathic pain. Diabetes Metab Syndr Clin Res Rev. 2017;11(1):31-35.
9. Alsalem M, Haddad M, Aldossary SA et al. Effects of dual peroxisome proliferator-activated receptors alpha and gamma activation in two rat models of neuropathic pain. PPAR Res. 2019;2019:2630232.
10. Barrett AM, Lucero MA, Le T et al. Epidemiology , public health burden, and treatment of diabetic peripheraal neuropathic pain: a review. Pain Med 2007;8(suppl 2): S50-S62.
11. Sloan G, Shillo P, Selevarajah D et al. A new look at painful diabetic neuropathy. Diabetes Res Clin Pract. 2018;144:177-91.
12. Raskin P, Huffman C, Yurkewicz L et al. Pregabalin in patients with painful Diabetic Peripheral Neuropath using an NSAID for Other pain Conditions: A Double-Blind Crossover Study. Clin J Pain. 2016;32(3);203-210.
Presenting Author
Ashok Kumar Saxena
Poster Authors
Ashok Saxena
Prof. Dr. med.
University College of Medical Sciences, University of Delhi, Delhi -110095
Lead Author
Nimisha T & MD degree
university college of medical sciences, Delhi, India
Lead Author
Geetanjali T Chilkoti & MD degree
university college of medical sciences, Delhi, India
Lead Author
Basu Dev Banerjee & PhD degree
university college of medical sciences, Delhi, India
Lead Author
S.V. Madhu & DM degree
university college of medical sciences, Delhi, India
Lead Author
Topics
- Genetics