Effect of Metformin on Chronic Pain After Thoracic Surgery in Diabetic Patients

Metformin has been found to have more and more functions as a commonly used hypoglycemic drug in clinic. It has been found that metformin has anti-inflammatory, anti-tumor and lipid metabolism regulating effects. Basic studies have shown that metformin as an adjuvant drug combined with gabapentin and tramadol is safe and effective in patients with neuropathic pain. Postoperative chronic pain as a common complication has seriously affected the quality of life and mood of patients after surgery.Some studies have shown that chronic pain after partial operation manifests as neuropathic pain. The effect of metformin on chronic pain after thoracic surgery in patients with diabetes mellitus was observed in this experiment, which was compared with patients taking insulin to control blood sugar.

Study Overview

• Status: Unknown
• Conditions: Postoperative Chronic Pain
• Intervention / Treatment: Drug: Metformin

Detailed Description

The analgesic mechanism of metformin may include the following aspects:(1)Metformin relieves neuropathic pain mainly because it can activate adenosine monophosphate-activated protein kinase (AMPK), which plays a crucial role in pain regulation as an important endogenous kinase controlling energy metabolism.(2)In addition, metformin can also inhibit ERK signaling pathway, further inhibit sodium channel, prevent the development of peripheral sensitization and achieve the effect of relieving neuropathic pain. (3)Metformin has been shown to alleviate bone cancer pain in rats by reducing STAT3 phosphorylation.Clinical research in this field is limited to basic research and ethical requirements are rarely reported at home and abroad. Li Chunye et al. of Jiangsu University designed a clinical trial to compare the efficacy of metformin and gabapentin combined with tramadol on neuropathic pain. The results showed that metformin had a better effect.

The incidence of chronic pain after thoracic surgery is higher. Postoperative chronic pain is a complex pain. The nature and mechanism of chronic pain after thoracic surgery are still controversial. Some studies have shown that some chronic pain after thoracic surgery manifests neuropathic pain, the mechanism may be related to surgical incision, nerve injury caused by trauma and increased pain sensitization. Can metformin alleviate chronic pain after surgery? The research on this aspect is still blank at present.This study was designed as a prospective cohort study to observe whether there was a difference in the incidence of chronic pain after thoracoscopic lobectomy between patients taking metformin and patients injecting insulin to control blood sugar.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China
      • The Affiliated Hospital of Xuzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

200 diabetic patients undergoing elective thoracoscopic lobectomy in the Affiliated Hospital of Xuzhou Medical University.

Description

Inclusion Criteria:

1. Aged between 18 and 70
2. Diabetes history. Use metformin or insulin to control blood sugar
3. The type of operation is selective thoracoscopic lobectomy.

Exclusion Criteria:

1. Newly diagnosed diabetic patients at admission
2. Complication of severe cardiopulmonary diseases
3. Refuse to participate in this experiment
4. Participate in other trials
5. Patients with diabetic complications (including diabetic nephropathy, peripheral neuropathy, etc.)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Metformin; Patients use metformin to control blood sugar	Drug: Metformin; Patients use metformin to control blood sugar
Insulin; Patients use Insulin to control blood sugar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of chronic pain after operation	A VAS score greater than or equal to 3 is defined as the presence of chronic pain after surgery.	3 months after operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS score at extubation time, 12 hours and 24 hours after operation	A VAS score greater than or equal to 3 is defined as the presence of pain after surgery.	extubation time, 12 hours and 24 hours after operation
Neuropathic pain score and incidence at 3 months after operation	Assessment of the presence of neuropathic pain by using self-rating scale	3 months after operation
Anxiety and Depression Score	Assessment of Anxiety and Depression in Patients by HAMD Depression Scale	3 months after operation
Length of ICU stay	Some patients may need to be transferred to ICU.	an average of 2 days
Length of hospital stay	Total length of hospitalization	an average of 10 days

Collaborators and Investigators

• Sponsor: Xuzhou Medical University
• Investigators: Study Director: JinDong Liu, M.S, Afliated Hospital of Xuzhou Medical University

Publications and helpful links

General Publications

• Shiers S, Pradhan G, Mwirigi J, Mejia G, Ahmad A, Kroener S, Price T. Neuropathic Pain Creates an Enduring Prefrontal Cortex Dysfunction Corrected by the Type II Diabetic Drug Metformin But Not by Gabapentin. J Neurosci. 2018 Aug 15;38(33):7337-7350. doi: 10.1523/JNEUROSCI.0713-18.2018. Epub 2018 Jul 20.
• Pecikoza UB, Tomic MA, Micov AM, Stepanovic-Petrovic RM. Metformin Synergizes With Conventional and Adjuvant Analgesic Drugs to Reduce Inflammatory Hyperalgesia in Rats. Anesth Analg. 2017 Apr;124(4):1317-1329. doi: 10.1213/ANE.0000000000001561.
• Smith B, Ang D. Metformin: Potential analgesic? Pain Med. 2015 Dec;16(12):2256-60. doi: 10.1111/pme.12816. Epub 2015 May 29.
• Ge A, Wang S, Miao B, Yan M. Effects of metformin on the expression of AMPK and STAT3 in the spinal dorsal horn of rats with neuropathic pain. Mol Med Rep. 2018 Apr;17(4):5229-5237. doi: 10.3892/mmr.2018.8541. Epub 2018 Feb 1.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 10, 2019
• Primary Completion (ANTICIPATED): December 9, 2019
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: September 12, 2019
• First Submitted That Met QC Criteria: September 12, 2019
• First Posted (ACTUAL): September 13, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 13, 2019
• Last Update Submitted That Met QC Criteria: September 12, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: XYFY2019-0003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual Participant Data(IPD) will be available when this trial is finished and the article have been published.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No