Post-operative pain is an enormous problem. Currently 10% of Americans will develop chronic pain following surgery, despite adequate tissue healing. In hand surgery, about 20% of patients who undergo carpal tunnel release have prolonged post-operative pain. Surgeons have tried changing their technique with little improvement in the rate of post- operative pain. There is now a growing body of literature that suggests that the dominating factors, determining whether acute pain will progress to chronic pain, are patient specific factors rather than factors of surgical technique. For example, in humans, fear, anxiety, and depression reflect brain physiology that appears to have a significant impact on pain. Glial cell activation may explain why these supraspinal states best predict who will develop post-injury chronic pain. Glial cells are non-neuronal cells that play an active role in modulating the activation of the central and peripheral nervous system. This study looks at whether a pharmacologic intervention that would "prep" glial cells can reduce post-operative pain after carpal tunnel release. The drug to be studied will be minocycline, a tetracycline antibiotic that is a glial cell inhibitor and in animal models, minocycline has shown promise inhibiting neuropathic pain This study's hypothesis is that subjects who take peri-operative minocycline will have faster time to pain resolution after carpal tunnel release. This will be a randomized placebo controlled trial. All participants will be veterans undergoing carpal tunnel release at the Palo Alto VA using local anesthetic. Participants will be randomized and those in the intervention arm will receive 200mg of minocycline at least 1 hour prior to their procedure and then 100mg twice a day for 5 days. All subjects will be called daily and asked about their level of pain and pain medication use. We will have two primary endpoints. The primary will be the Time-to-Pain-Resolution (TPR) defined as zero 24- hour average pain for three consecutive days, as assessed by a daily-administered Brief Pain Inventory. The second will be time-to-prescription-opioid-cessation defined as the zero use of prescription opioids for three consecutive days. We plan to explicitly study pain chronicity by using TPR as our primary endpoint and survival analysis to identify predictors of transitioning from acute to chronic pain. This novel work could open new pathways to managing surgical patients and have a profound impact on veterans who undergo elective surgery.

Public Health Relevance

Carpal tunnel syndrome is a large problem for the VA health system with over 127,000 veterans diagnosed and 10,000 having surgical releases in 2007. The incidence of carpal tunnel syndrome increases with age and diabetes, which means that the aging VA population will continue to have a high rate of carpal tunnel syndrome (CTS). The most effective treatment for CTS is surgery but 20% of patients suffer chronic pain. The VA, the surgeon, and the patient are all interested in limiting post-operative pain to decrease the morbidity of this procedure and provide quicker return of function. This study may lead to a new prophylactic pain treatment for carpal tunnel surgery and possibly impact recovery of veterans undergoing all other types of surgery.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
1I01RX000487-01A1
Application #
8198349
Study Section
Musculoskeletal/Orthopedic Rehabilitation (RRD2)
Project Start
2012-04-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2014-03-31
Support Year
1
Fiscal Year
2012
Total Cost
Indirect Cost
Name
Veterans Admin Palo Alto Health Care Sys
Department
Type
DUNS #
046017455
City
Palo Alto
State
CA
Country
United States
Zip Code
94304