Low back pain (LBP) is a complex condition that affects 65-85% of the population, and is the leading musculoskeletal condition contributing to disability in the United States. Seventy-five percent of individuals undergoing treatment for this condition experience suboptimal or poor outcomes in the form of disability and deficits in functional capacity, including strength and endurance of the lumbar musculature. The most common initial treatments for individuals with chronic LBP are exercise-based rehabilitation, and pharmacological management in the form of analgesic medications. Although these two conservative treatment modalities are often concurrently prescribed, the influence of analgesic medications on the capacity of muscle to adapt in response to exercise is unknown. Importantly, in healthy individuals, some of these medications have been shown to inhibit muscle protein synthesis, metabolism, and stem cell function. The influence of medications may explain the variability in muscle- specific and clinical outcomes associated with exercise-based rehabilitation in this population. To address these current gaps in the literature, we propose to define medication usage patterns and clinical outcomes across individuals with chronic low back pain who are participating an exercise-based rehabilitation program. Specific Aim 1 will investigate the influence of symptom interference, psychosocial factors, and diagnosis on analgesic medication use relative to exercise in individuals with LBP. Specific Aim 2 will evaluate the influence of medication type, dose, and timing on exercise performance. Finally, Specific Aim 3 will determine if medication type, dose, and timing influences the magnitude of muscle hypertrophy and clinical outcomes after completion of a 12-week resistance exercise program. Determining the impact of common analgesic medications on muscle hypertrophy, exercise performance, and clinical outcomes is an important step in optimizing conservative management in individuals with low back pain. This information will also be applicable to a variety of musculoskeletal conditions for which similar treatment strategies are employed. This contribution is significant because it is the first step in a precision medicine approach aimed at establishing appropriate and targeted exercise and analgesic medication prescriptions for reversing muscle impairments that obstruct patient recovery. This proposal is innovative because it aims to fill a large gap in knowledge regarding the influence of analgesic medication on muscle adaptation in individuals with pain and pathological muscle.