Pain Study to See if Ultram ER Will Provide Relief to Subjects Whose Pain is Not Well Controlled by Narcotics

The study consists of 6 visits over 6 weeks. Study testing includes: physical exam, urine
testing, questionnaires and non-invasive (no needles) nerve testing using cold/heat
sensations. Compensation and some parking reimbursement provided.

Inclusion Criteria:

1. Subject will be between ages 18 to 65 years in all three groups.

2. Subject has NOT been on Tramadol or Tramadol ER for at least one month.

3. Subject has NOT been on tricyclic antidepressants, serotonin, norepinephrine, or mixed
serotonin/norepinephrine reuptake inhibitors (SSRI/SNRI), or muscle relaxant with
potential action as an SSRI or SNRI (e.g., Flexeril) for at least one month. Subject
has not been on monoamine oxidase inhibitors in the past 14 days.

4. Subjects should have had a stable pain condition (e.g., axial low back pain as listed
below in item # 5-7) for at least three months. This requirement is set in order to
avoid clinical uncertainty from an unstable pain condition and to minimize the study
variation.

5. Axial low back pain refers to pain conditions resulting from myofascial disorder,
lumbar facet joint disease, discogenic disease, and postlaminectomy syndrome. Patients
with neurological signs (weakness or numbness) will not be included in the study
because of potential confounding effects on the QST assessment of pain threshold and
pain tolerance.

6. Headaches refer to migraine, tension, or cluster headache, cervicogenic pain (e.g.,
facet joint disease, myofascial pain), and trigeminal neuralgia. However, patients
with neurological diseases including multiple sclerosis, amyotrophic lateral
sclerosis, and stroke will not be included due to possible neurological deficits that
may confound the QST assessment.

7. Abdominal and pelvic pain refers to pain from abdominal and/or pelvic organs (e.g.,
chronic pancreatitis, endometriosis).

8. Subject is willing to have his/her opioid dose tapered.

9. Female subjects of childbearing potential must have a negative urine pregnancy test at
the initial visit.

Exclusion Criteria:

1. Subject has sensory deficits at the sites of QST. Sensory deficits refer to such
changes resulting from neurological diseases or medical conditions causing peripheral
polyneuropathy and sensory changes, which include but are not limited to diabetes,
alcoholic neuropathy, AIDS neuropathy, thyroid disease, severe liver or kidney
disorders.

2. Subject has scar tissue, infection, or acute injury at the sites of QST.

3. Subject has had interventional procedures that may alter the results of QST. Such
procedures include neuroablation (chemical or electrothermal) at any time, neuraxial
(e.g., epidural) or local anesthetic block within the last eight weeks, and lumbar
sympathetic or hypogastric block within the last six months. We consider eight weeks
and six months as the minimal time period that must have elapsed after neuraxial
injection and lumbar sympathetic block, respectively, in order to minimize the
possible influence from a previous interventional procedure.

4. Subject has a pending litigation related to his/her chronic pain condition.

5. Subject has a history of or current seizure disorder.

6. Subject has a history of severe allergic reaction to Tramadol ER or other opioid
medications.

7. Subject has a major psychiatric disorder (major depression; bipolar disorder;
schizophrenia; anxiety disorder; psychotic disorders; eating disorders; alcohol or
drug dependence; attention deficit hyperactivity disorder); subject with any known
history of such conditions also will be excluded.

8. Subject has severe renal impairment or severe hepatic impairment.

9. Subject is using illicit drugs detected through the urine toxicology screen.

10. Subject is pregnant or lactating.