Effect of Ketamine on Opioid-Induced Hyperalgesia

We hypothesize that:

1. Chronic pain patients on chronic opioids would have a lower pain threshold and lower
pain tolerance when compared to opioid naïve patients (patients with chronic pain with
non-opioids treatment)., as measured by QST in a non-affected neutral limb;

2. Chronic pain patients on chronic opioids would have an increased response to painful
stimulation, so called "windup" as demonstrated by QST;

3. Both "wind-up" and altered pain threshold and tolerance would be indicative of the
presence of opioid-induced hyperalgesia;

4. Intravenous ketamine, an NMDA receptor antagonist, could be used to differentiate
between opioid-induced hyperalgesia and opioid tolerance.

Inclusion Criteria for Group 1

1. Subject will be between ages 18 to 65 years.

2. Subject has a chronic pain condition for at least three months. This requirement is
set in order to avoid the clinical uncertainty of an unstable pain condition and to
minimize the study variation. Subjects should have a VAS pain score at 4 or above at
the time of study.

3. Subject is on a chronic opioid treatment regimen (e.g., morphine, fentanyl, oxycodone,
methadone, hydromorphone, hydrocodone) for at least three months. There should have
been no changes in the type and amount of opioid dose for at least one month. Only
patients with a minimal daily dose of at least 60 mg morphine equianalgesic dose will
be included.

Inclusion Criteria for Group 2

1. Subject who meets the criteria #1 & #2 as listed for Group 1.

2. Subject has not been on an opioid regimen for the last three or more months.

Exclusion Criteria for all groups:

1. Subject has an altered sensation at the skin site of QST (one of upper extremities).

2. Subject has scar tissue or acute injury at the skin site of QST.

3. Subject has neurological disease or a condition causing upper extremities or
generalized polyneuropathy, such as diabetic neuropathy, alcoholic neuropathy, AIDS
neuropathy, multiple sclerosis, amyotrophic lateral sclerosis, and post-stroke
residual neurological deficits.

4. Subject has a diagnosis of renal or liver failure.

5. Subject has a diagnosis of unstable angina, congestive heart failure, cardiac
arrythmias or myocardial infarction within 1 year.

6. Subject is allergic to ketamine.

7. Subject had recent therapy that may influence QST results, e.g., neuroablative
procedure involving upper extremities within six-months or peripheral neurolytic block
involving upper extremities within two-months.

8. Subject has a confirmed diagnosis of and is under the care of a psychiatrist for major
depression disorder, eating disorder; alcohol or drug dependence; or attention deficit
hyperactivity disorder. Subject has any history of a confirmed diagnosis of bipolar
disorder, schizophrenia, anxiety disorder or a psychotic disorder

9. Subject is tested positive on drug urine screening test.

10. Subject is pregnant or breast-feeding.