This is a prospective randomized controlled trial that will assess preoperative, perioperative, and long-term oxidative stress (OS); pain; and functional outcomes over a 12 month period and test the hypothesis that a potent antioxidant intervention (glycine + N-acetyl-cysteine(GlyNAC)) reduces oxidative stress and chronic post surgical pain (CPSP) in patients undergoing total knee arthroplasty (TKA).

One of the most common surgical procedures performed in older adults is total knee arthroplasty (TKA), with an estimated 1 million TKAs performed annually in the United States. TKA directly addresses the pathology underlying knee joint pain and mobility limitations resulting from osteoarthritis. For most patients, TKA is effective for pain reduction and increasing function. However, a subgroup of 15-20% of TKA patients report unsatisfactory long-term pain outcomes well after postsurgical healing has occurred despite technical success of the procedure. Chronic postsurgical pain (CPSP) following TKA has been reported to be worse than the preoperative pain in 7% of TKA patients at up to 4-years. A potential biological mechanism is perioperative oxidative stress (OS),

The proposed project seeks to confirm the mechanistic role of OS in post-TKA CPSP and test the hypothesis that a perioperative intervention to reduce OS may reduce risk for CPSP post-TKA. This is a prospective randomized controlled trial that will assess preoperative, perioperative, and long-term oxidative stress (OS); pain; and functional outcomes over a 12 month period and test the hypothesis that a potent antioxidant intervention (GlyNAC) reduces OS and CPSP in patients undergoing total knee arthroplasty (TKA).

Inclusion Criteria:

• Age 50 or older
• Intact cognitive status and ability to provide informed consent (based on cognitive screening with the Mini Mental State Examination)
• Ability to read and write in English sufficiently to understand and complete study questionnaires
• Undergoing unilateral primary TKA
• Medical diagnosis of osteoarthritis
• Past 24 hour worst numeric rating scale (NRS) pain of at least 4/10.

Exclusion Criteria:

• Diagnosis of pre-existing neuropathy
• Untreated hypo/hyperthyroidism
• Untreated heart disease
• Alanine transaminase/aspartate transaminase >2x upper-limit of normal range
• serum creatinine >1.5 mg/dl
• Pregnancy
• Complex Regional Pain Syndrome (CRPS) diagnosis prior to undergoing TKA
• Presence of lower extremity vascular disease, inflammatory or autoimmune disorders, or malignancy
• Presence of current clinically significant chronic pain conditions outside of the lower extremity ( daily pain for >3 months and greater ≥3/10 in intensity or the focus of medical care)
• Presence of other medical conditions that in the opinion of the orthopedic surgeon co-investigators would make a patient's study participation unsafe

Key data elements will be preserved in final analyzed form (e.g., combined OS outcomes [mean of the two OS assays above], summary scores on all measures). The study protocol, standardized data collection instruments, and data dictionary will be uploaded in the repository. to facilitate study interpretation. Shared data will be uploaded in SPSS format.

Data from the project will be stored within the Open Science Framework (OSF) database. OSF provides a unique URL for all datasets which will be provided for those interested. OSF also includes an interface with a search engine for identify datasets by topic/keyword.

The data will be made available in OSF upon publication of the project findings. The data will continue to be available indefinitely on OSF subject to any OSF limitations. The dataset will be de-identified, so there will be no privacy limitations. Data will be accessible after publication of project results so there will be no limits on re-use.

The data will be made available in OSF upon publication of the project findings.

OSF provides a unique URL for all datasets which will be provided for those interested. OSF also includes an interface with a search engine for identify datasets by topic/keyword.