Managing Chronic Tendon Pain by Repurposing Metformin
Abstract
Chronic pain due to overuse injury to tendon, a soft tissue that connects muscle to bone, is a highly prevalent debilitating health care problem that is very costly. It is common in individuals who participate frequently in intense physical training as well as individuals who perform repetitive tasks combined with physical strains. This can include active-duty military personnel in both combat and non-combat roles, Veterans, people in certain occupation, and athletes. Musculoskeletal injuries (MSIs) induced by overuse/overload affect tendons, bones, joints, ligaments, and muscles causing pain. Achilles tendon, the largest and strongest tendon in the body, is highly prone to such overuse/overload injury. Each year at least 100,000 individuals sustain Achilles tendon injuries, with a yearly total of 16.4 million total tendon and ligament injuries in the United States. Tendon overuse injuries, or tendinopathies, are a major problem among military personnel, with MSIs as the leading cause of disability and decreased military readiness among Warfighters. Thus, chronic pain management in tendon overuse injury is needed in order to not only preserve the fighting force by accelerating return to duty for injured military personnel but also improve Warfighter readiness as well. The currently available treatment options such as RICE (rest, ice, compression, elevation) provide only short-term relief that is not targeted against the root cause of tendinopathy. Commonly prescribed pain medications and corticosteroid injections negatively affect the healing and repair of injured tendons. Moreover, such treatments pose risks that range from common side effects (nausea, vomiting, diarrhea, dizziness) to more serious effects such as stomach ulcers, bleeding, and kidney and liver failure. Currently there is no effective therapy to manage tendon pain or proper repair of tendon after overuse injury. Therefore, we aim to develop a novel therapy that is safe, effective, economic, and easy to administer for the management of tendon pain and promotion of tendon healing and repair after overuse injury. Metformin (Met) is a well-known U.S. Food and Drug Administration-approved oral drug for the treatment of diabetes. Besides glucose-lowering effects, Met has other properties, which include reduction of pain and inflammation and promotion of tissue healing. Our group has been actively involved in tendon overuse injury research for the past two decades. We have shown that intraperitoneal injection of Met is effective in reducing tendon inflammation and degeneration in our animal model of tendinopathy by inhibiting HMGB1, a tissue damaging molecule that is also a mediator of pain and inflammation. Some clinical studies in osteoarthritis and rheumatoid arthritis patients also have shown the beneficial effects of oral ingestion of metformin (OIM) in reducing pain, inflammation, and improving function of the joints (shoulder, elbow, wrist, knee etc.). In this exploratory clinical trial, we are planning to treat a small number of Achilles tendinopathy patients (n = 20) experiencing chronic tendon pain for at least 6 months with OIM. They will receive 2,000 mg Met, a standard dose used for diabetes patients, daily for up to 16 weeks along with physical therapy (PT). An equal number of patients as control group without OIM but with PT and placebo drug will be included. We will assess the effects of OIM at 4 and 16 weeks after starting the therapy by using the standard pain questionnaires and functional tests (jumping, hopping, toe raises, etc.) used in clinics and examine tendon structural integrity using ultrasound imaging. We will use the same assessment methods before the start of OIM treatment to collect baseline data for comparisons to evaluate recovery. OIM is currently prescribed in clinics for diabetes treatment, not for the treatment of tendinopathy. Our results for the first time will provide guidelines to pain managemen
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310712
Entities
People
- James Wang
Organizations
- United States Army