Patient case (clinical description): A 66-year-old woman comes to the office due to joint pain in the hands and periodic morning stiffness that lasts less than 15 minutes.  The pain is moderately severe and worsens with daily activity. The patient used Tylenol with minimal relief.  Past medical history is notable for hypertension and hypercholesteremia.  Physical examination shows firm nodules over the distal interphalangeal joints, bilaterally. The patient has pain in her knees as well. The knees are stiff in the morning for less than 30 minutes and become worse with climbing stairs. She has some sensation of bone friction during activity. X-ray shows narrowing of the joint space, subchondral bone sclerosis and osteophyte formation along the joints.

Patient's own account: I'm a 66-year-old woman and I went to my doctor's office because of a bloody joint pain in my hands that has been lasting for a while. The pain comes and go in the morning usually. I feel like a stiffness that last less than 15 minutes. The pain is moderately severe but it gets worse when I'm using my hands. I used Tylenol which helped a little. Apart from that, I suffer from hypertension and high cholesterol. The doctor made me notice that I have bumps around both of my hand joints. I also suffer from my knees and they are also stiff in the morning for around 30 min. It's even worse when I climb up the stairs! I also feel like my bones are rubbing against each other when I'm moving. The X-ray showed that I have narrow joint space, I have sclerosis, and abnormal growths of bone along my joints.

Clinical trial: Milnacipran for Chronic Pain in Knee Osteoarthritis

Eligibility criteria:
Inclusion Criteria:

          -  Knee pain and osteophytes on radiographs OR

          -  Knee pain plus patient age of 40 years or older, morning stiffness lasting 30 minutes
             or less, and crepitus (cracking sound) during motion

          -  Experiences chronic pain for 6 months or longer

          -  Average pain rating of worse knee is equal to 4 or greater on a 0-10 scale

          -  If female, is not pregnant or breast feeding, and not currently attempting to
             conceive; if of childbearing potential, use of a highly effective method of birth
             control (as determined by Pl)

          -  Able to walk at least ½ a city block a day, and agrees to try and slowly increase that
             over the course of study

          -  Able to read and speak English and provide informed consent

          -  Able to understand and comply with all data collection methodology including
             electronic diary

          -  Subject agrees to 1) continue their stable drug regimen with no changes during the
             course of study, 2) only use Tylenol 325 mg of tablets (a maximum of 8 tablets a day)
             for breakthrough pain, and 3) not use Tylenol or any other pain medicines 12 hours
             before testing.

        Exclusion Criteria:

          -  Subject takes SNRIs (Savella, Cymbalta, Venlafaxine) or other neuroamine re-uptake
             blockers for mood disorders

          -  Subject is allergic to SSRIs, SNRIs, or milnacipran

          -  Subject has severe or untreated psychiatric disturbance (e.g. mania, depression,
             anxiety, substance dependence)

          -  Subject is medicated with 'triptans, MAOIs, SSRIs, other SNRIs, tricyclic or
             heterocyclic antidepressants, lithium, epinephrine, norepinephrine, clonidine or
             digoxin during the trial

          -  Subject has a clinical diagnosis of fibromyalgia

          -  Subject has severe ongoing or unaddressed medical conditions (e.g. Renal or Hepatic
             disease [creatinine>1.5 ml/dl; AST or ALT> 3x normal limit], uncontrolled
             hypertension, severe cardiac rate or rhythm disorders, rheumatologic disease (e.g.
             polymyalgia rheumatica), narrow angle glaucoma, hyponatremia, clotting disorders,
             uncontrolled seizure disorder or urinary retention)

          -  Subject has cardiac implants

          -  Subject has a knee replacement

          -  Subject plans to start new pain treatments or therapies during the study (e.g. new
             pain medication, injections, PT, surgery)
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 90 Years

Eligibility (NLI label): Entailment