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.

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.