489: mTORC1 and IL-6 mRNA Modulation After Mindfulness based intervention and Pregabalin in PHN: RCT

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic neuropathic pain, Neuroimmunology, Non-pharmacological treatments, Genetics and Epigenetics

Background and Aims: Background
Postherpetic neuralgia (PHN), chronic neuropathic pain persisting beyond three
months after herpes zoster and impairs QoL. Pregabalin partially relieves but is limited by adverse effects. Mindfulness-Based
Intervention (MBI) has demonstrated benefits in chronic pain; its role in PHN
and its impact on gene expression remain unexplored.
Primary Objectives
• Compare NRS-Pain and NPSI scores
between groups at baseline and at 1st, 2nd, 4th, and 8th weeks.
• Assess changes in mRNA expression of mTORc1 and IL-6 genes.
Secondary Objectives
• Proportion of patients achieving NRS-Pain ≤3
• NRS-Sleep scores
• Pain Catastrophizing Scale (PCS)
• Quality of Life (SF-12)

Methods: This RCT included 50 patients with confirmed PHN, randomized into
two groups (n=25):
• Group PO: Pregabalin 75 mg BD for 8 weeks
• Group PM: Pregabalin 75 mg BD plus daily 20-minute Mindfulness-Based
Intervention for 8 weeks
Clinical parameters (NRS-Pain, NPSI, NRS-Sleep, PCS, SF-12) recorded at baseline and
at weeks 1, 2, 4, and 8.
Venous blood samples (3 mL) collected at baseline and at 8 week. Total RNA
was extracted, reverse-transcribed into cDNA, and quantitative RT-PCR performed to
evaluate mTORc1 and IL-6 gene expression, with β-actin as the housekeeping gene.
Statistical analysis done using SPSS v21. p-value <0.05 considered
statistically significant.

Results: Demographics comparable.

NRS-Pain decreased significantly in both groups (p<0.001), with greater reduction in Group PM 2nd week onward and more patients achieving NRS ≤3.

Total NPSI declined in both groups, with higher reduction in Group PM (62.2% vs 48.44%), including significant improvement in electric-shock, burning, pins-and-needles, and allodynia. NRS-Sleep and PCS improved significantly, with greater PCS reduction in Group PM (74.5% vs 44.5%, p<0.001). SF-12 scores improved more in Group PM (p<0.001).

mTORc1 (1.83-fold; p=0.042) and IL-6 (1.46-fold; p=0.001) significantly downregulated in Group PM, with significant intergroup differences (p=0.027). Rescue analgesia significantly lower in group PM.

Conclusions: The efficacy of Pregabalin plateaus due to dose-limiting adverse effects. Specifically emphasising Mindfulness-Based Intervention modulates central pain processing regions-anterior cingulate cortex, insula, and prefrontal cortex-influencing emotional regulation and reducing psychological distress. Integrated approach exerts synergistic effects addressing peripheral & central sensitization and cognitive-emotional modulation.

Significant downregulation of mTORc1 and IL-6 gene expression suggests potential
molecular basis for enhanced clinical outcomes.

Integrated approach of pregabalin with Mindfulness-Based Intervention is significantly
superior to pregabalin monotherapy in managing neuropathic pain in PHN. It provides
enhanced pain relief, improved sleep, reduced catastrophizing, improved QoL,
decreased rescue analgesia, and significant modulation of inflammatory gene
expression.

References: 1. Devigili G, Lombardi R, Lauria G, Cazzato D. The evolving landscape of small fiber neuropathy. InSeminars in Neurology 2025 Feb (Vol. 45, No. 01, pp. 132-144). Thieme Medical Publishers, Inc..

2. Fan CY, McAllister BB, Stokes-Heck S, Harding EK, de Vasconcelos AP, Mah LK, Lima LV, van den Hoogen NJ, Rosen SF, Ham B, Zhang Z. Divergent sex-specific pannexin-1 mechanisms in microglia and T cells underlie neuropathic pain. Neuron. 2025 Mar 19;113(6):896-911.

3. Saxena AK, Choudhary S, Chilkote G. Gene expression signature of neuropathic pain: Unveiling compassion through pain genetics and genome-wide mRNA profiles. Indian Journal of Anaesthesia. 2024 Nov 1;68(11):937-40.

4. Saxena AK, Singh A, Chilkoti GT, Sharma T, Banerjee BD, Das S, Singhal A. Modulation of signal transduction gene expression following pulsed radiofrequency in dorsal root ganglia and pregabalin therapy. Pain Management. 2022 Apr 1;12(3):347-56.

5. Saxena AK, Bhardwaj N, Chilkoti GT, Malik A, Thakur GK, Bajaj M, Banerjee A, Banerjee BD, Singal A. 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. Pain medicine. 2021 Oct 1;22(10):2276-82e.

Presenting Author: Ashok Kumar Saxena
Submitting Author: Ashok Kumar Saxena

Senior Author: Ashok Kumar Saxena

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Shilpa Babu: MD - Department of Anaesthesiology, Critical Care and Pain Medicine, University College of Medical Sciences (University of Delhi) & Guru Teg Bahadur Hospital, Delhi – 110095, India
• Geetanjali T Chilkoti: MD - Department of Anaesthesiology, Critical Care and Pain Medicine, University College of Medical Sciences (University of Delhi) & Guru Teg Bahadur Hospital, Delhi – 110095, India
• Archana Singhal: MD - Department of Anaesthesiology, Critical Care and Pain Medicine, University College of Medical Sciences (University of Delhi) & Guru Teg Bahadur Hospital, Delhi – 110095, India
• Shukla Das: MD - Department of Anaesthesiology, Critical Care and Pain Medicine, University College of Medical Sciences (University of Delhi) & Guru Teg Bahadur Hospital, Delhi – 110095, India
• Rajeev Kumar Malhotra: PhD - AIIMS New Delhi