Inclusion Criteria:  Have a visual analog scale (VAS) pain value ≥40 and <95 during screening. Have a history of daily pain for at least 12 weeks based on participant report or medical history. Have a body mass index <40 kilograms per meter squared (kg/m²) (inclusive). Are willing to maintain a consistent regimen of any ongoing nonpharmacologic pain-relieving therapies (for example, physical therapy) and will not start any new nonpharmacologic pain-relieving therapies during study participation. Are willing to discontinue all medications taken for chronic pain conditions or the duration of the study. Are at 40 years old or older at the time consent is signed. Have presence of index knee pain for >12 weeks at screening. Have an x-ray supporting diagnosis of osteoarthritis according to the American College of Rheumatology with a Kellgren-Lawrence grade 2 to 4 radiographic classification of index knee. Are men, or women able to abide by reproductive and contraceptive requirements.  Exclusion Criteria:  Have had a procedure within the past 6 months intended to produce permanent sensory loss in the target area of interest (for example, ablation techniques). Have surgery planned during the study for any reason, related or not to the disease state under evaluation. Have, in the judgment of the investigator, an acute, serious, or unstable medical condition or a history or presence of any other medical illness that would preclude study participation. Have had cancer within 2 years of baseline, except for cutaneous basal cell or squamous cell carcinoma resolved by excision. Have fibromyalgia Have a substance use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition; DSM-5; American Psychiatric Association). Have a positive human immunodeficiency virus (HIV) test result at screening. Are in the judgment of the investigator, actively suicidal and therefore deemed to be at significant risk for suicide. Have an intolerance to acetaminophen or paracetamol or any of its excipients. Have a history of alcohol, illicit drug, analgesic or narcotic use disorder within 2 years prior to screening. Are largely or wholly incapacitated and unable to participate fully in all protocol procedures, for example, bedridden or confined to a wheelchair, permitting little or no selfcare. Have presence of surgical hardware or other foreign body in the index knee. Have an unstable index joint (such as a torn anterior cruciate ligament). Have had a surgical procedure or therapeutic injection in the affected knee within 3 months prior to starting the washout period. Have chronic pain syndrome, or other concurrent medical or arthritic conditions that could interfere with the evaluation of the index knee. Have a history of Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, sarcoidosis, or amyloidosis. Have clinical signs and symptoms of active knee infection or crystal disease of the index knee. Have a history of infection in the index joint. Have a history of arthritis due to crystals (e.g., gout, pseudo gout). Have pain or functional impairment due to ipsilateral hip osteoarthritis. Are pregnant or breastfeeding.