• Change in Pain Severity on 0-10 Numeric Rating Scale [ Time Frame: 2- or 3-month ]
  
• Change in Pain Severity on 0-10 cm VAS [ Time Frame: 2-/3-months ]
  
• Change in Pain Severity on WOMAC Pain Subscale (0-100) [ Time Frame: 2-/3-months ]
  

• Patient global assessment of response to treatment. [ Time Frame: 2-/3-months ]
  
• Physician global assessment of response to treatment [ Time Frame: 2-/3-months ]
  
• Improvement in Physical Function subscale of the WOMAC and WOMAC total [ Time Frame: 2-/3-months ]
  
• Qualitative assessment of pain relief [ Time Frame: 2-/3-months ]
  
• Time to Onset of Pain Relief and duration of pain relief [ Time Frame: Upto 6-month data ]
  
• Change in joint function as measured by active and passive range of motion, time for 50-feet walk and Time to perform sit to stand 10 times without using arms to push up (Timed Stands Test) and Timed up-and-go (TUG) tests [ Time Frame: Time of Maximum improvement upto 6-months ]
  
• QOL: generic health status measure, the SF-36 and specific health status measures, the WOMAC [ Time Frame: 2-/3-months ]
  
• Clinical assessment of joint erythema, warmth, swelling and tenderness [ Time Frame: Upto 6 months ]
  
• Manual muscle strength testing of flexion and extension. [ Time Frame: Upto 6-months ]
  
• Clinically important change in pain (at least a 2-point or 30% decrease in pain severity on 0-10 Numeric rating scale (NRS)) at 2-mo follow-up (FU) visit [ Time Frame: 2-/3-months ]
  
• Minimal Clinically Important Improvement (MCII) on WOMAC physical function subscale [ Time Frame: 2-/3-months ]
  
• Baseline Serum and Joint Fluid Cytokine Levels [ Time Frame: Baseline values ]
  
• Change in Serum and Joint Fluid Cytokine Levels [ Time Frame: Baseline to time of maximum or no pain relief ]
  

This 6-month randomized, placebo-controlled, double blind trial will compare a single intra-articular (IA) injection of 100 units of Botulinum Toxin A (BoNT/A) to placebo for improvement in pain, function and quality of life (QOL), and safety in patients with painful total knee arthroplasty (TKA). Patients will be recruited at the Minneapolis VA Medical Center. Patients will be eligible if they are over age 18, have TKA, have pain ≥6/10 on 0-10 numeric rating scale (NRS) and are not candidates for revision surgery. The primary outcome is: (1) change in pain severity (on 0-10 NRS) 2 months after IA injection; Secondary outcomes that will be assessed at each follow-up (FU) visit include: (1) clinically meaningful pain relief (≥2-point or ≥30% decrease in pain severity on 0-10 NRS) 2 months after IA injection; (2) or (2) Minimal Clinically Important Improvement on Western Ontario MacMaster Arthritis Index (WOMAC) function subscale 2 months after IA injection; (3) amount of pain relief; (4) patient and physician global assessment of response; (5) QOL assessed by WOMAC and Short-form 36 (SF-36) scores; (6) change in function by Timed Stands Test (TST) and Timed-up-and-go (TUG) tests. We will determine time to onset of and duration of pain relief and time to improvement in function. Safety will be assessed by structured interview form for adverse effects, sensory and manual muscle strength testing, and index joint examination for swelling, erythema and tenderness.

At visit #1, after informed consent and screening for inclusion/exclusion criteria, patients will undergo: index joint X-ray, laboratory tests; history, physical examination, index joint pain history, comorbidity and medication history; patient pain assessments, WOMAC and SF-36; and blinded index joint, neurological examination, TST and TUG tests. 50 patients will be randomized to receive either IA BoNT/A 100 units or sterile saline in the index joint. FU phone interviews at 2 and 4-weeks will include pain assessments, WOMAC, patients' global assessment and adverse effects. Interim visits at 2, 3 and 4-months will be identical to visit #1, but will also include patients' and physicians' global assessment and there will be no joint injection. End of study visit at 6 months will be identical to interim visits with the addition of index joint X-ray and laboratory tests.

Multiple analysis of variance and generalized estimating equations will be used for analysis of continuous and categorical outcomes respectively. Chi-square tests will be used to compare frequency of adverse events. Analysis will be intention-to-treat with last observation carried forward for missing data.

Inclusion Criteria:

• Male or female subjects, 18 years of age or older.
• Written informed consent and written authorization for use or release of health and research study information have been obtained.
• Subject has chronic Prosthetic knee joint pain for more than 3 months.
• Subject has pain 6 or greater on a 10 point Numerical Pain Rating scale
• Ability to follow study instructions and likely to complete all required visits.
• Negative urine pregnancy test on the day of treatment prior to the administration of study medication (for females of childbearing potential). (if applicable)
• Negative infectious etiology workup (joint aspiration, serological parameters such as Erythrocyte Sedimentation Rate (ESR) or C-reactive protein (CRP) and clinical examination).
• Patients who were considered not to be candidates for Prosthetic knee joint revision surgery and have failed traditional treatments including oral pain medications, as determined by referring orthopedic surgeon

Exclusion Criteria:

• Use of aminoglycoside antibiotics, curare-like agents, or other agents that might interfere with neuromuscular function.
• Any medical condition that may put the subject at increased risk with exposure to BOTOX ®including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or known disorders of neuromuscular function
• Females who are pregnant, breast-feeding, or planning a pregnancy during the study or who think that they may be pregnant at the start of the study, or females of childbearing potential who are unable or unwilling to use a reliable form of contraception during the study.
• Know allergy or sensitivity to any of the components in the study medication.
• History of recent or ongoing alcohol or drug abuse.
• Known, uncontrolled systemic disease.
• Concurrent participation in another research study
• Any condition or situation that, in the investigator's opinion, may put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study.
• Patients whose pain is rated as less than 6 on a 10 point Numerical Pain Rating scale at the screening visit