Healthy
Conditions
Keywords
healthy volunteers, analgesia, pain, Healthy subjects
Brief summary
This research study is being done because pain is a significant problem for patients with a variety of medical problems and following surgery or traumatic injury. Currently available pain medications may not treat all types of pain or may treat pain only at doses that produce side effects and complications. The medication in this study may have a role in better treatment of pain. The goals of this study are to see if a dose of ketorolac (non-narcotic, pain reliever), given into the fluid in the back near the spine has any effect on pain or discomfort in the skin sensation that will take place after applying capsaicin (chili pepper) cream. The sunburn-like sensation that people experience after having capsaicin cream applied is similar to, but much milder than, the pain that some people have after surgery and after certain types of nerve injuries. This study will test the effects of combining two medications that are often given together to control postoperative pain or pain from a nerve injury. The investigators are especially interested in answering two questions about the effects of ketorolac (non-narcotic pain reliever) and remifentanil (intravenous \[IV\] narcotic painkiller): 1. How much does remifentanil (narcotic painkiller) affect the sunburn-like painful area on your skin, which develops after applying capsaicin cream? 2. What pain relieving effects does spinal ketorolac have when given with IV remifentanil?
Detailed description
Intravenous (IV) remifentanil stimulates spinal COX activity, leading to increased Cerebrospinal fluid CSF) prostaglandin E2 (PGE2) concentrations and areas of capsaicin-induced mechanical hypersensitivity after remifentanil infusion, and these effects will be blocked by intrathecal ketorolac. Areas of mechanical hyperalgesia and allodynia will be established by topical capsaicin + intermittent heat in healthy volunteers, who will be randomized to receive intrathecal saline or ketorolac during remifentanil infusion, with primary outcome measure area of hyperalgesia and secondary outcome measure Cerebrospinal fluid (CSF) prostaglandin E2 (PGE2) concentration after stopping remifentanil.
Interventions
DRUGketorolac
single intrathecal injection of ketorolac 2 mg
DRUGplacebo
subject will receive a placebo (preservative free normal saline) spinal injection
DRUGremifentanil
All subjects will receive a remifentanil infusion
DRUGCapsaicin
Topical capsaicin pain model utilized for each subject
Sponsors
National Institute of General Medical Sciences (NIGMS)
Wake Forest University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy * American Society of Anesthesiologist (ASA) I or II classification * between the ages of 18-55 * weigh less than 250 pounds * without chronic pain
Exclusion criteria
* taking analgesics in the last 2 weeks * positive urine drug screen * pregnancy * currently taking any prescription antidepressants or other medications that are mood altering * liver or kidney disease * stomach ulcers * allergies to ketorolac, lidocaine, or capsaicin cream * lung disease (COPD)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hyperalgesia | 24 hours | Total Area of hypersensitivity (measured in centimeters) were assessed approximately 24 hours post intrathecal ketorolac injection by the method of using a von Frey filament |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cerebrospinal Fluid (CSF) Prostaglandin E2 (PGE2) Concentration | 2.5 hours | Concentration of prostaglandin E2 (PGE2) in Cerebrospinal fluid (CSF) 2.5 hours post injection of intrathecal ketorolac |
Countries
United States
Participant flow
Recruitment details
31 healthy subjects between the ages of 19-51 were recruited and 30 were randomized between the dates for 11/20/2007 and 8/17/2010. Subjects were seen for all study related visits in the General Clinical Research Center at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.
Participants by arm
| Arm | Count |
|---|---|
| Intrathecal Ketorolac In the presence of a remifentanil infusion subject will receive a single intrathecal injection of ketorolac 2 mg | 14 |
| Placebo Intrathecal Injection In the presence of remifentanil the subject will receive a single intrathecal injection of placebo (preservative-free normal saline) | 16 |
| Total | 30 |
Baseline characteristics
| Characteristic | Placebo Intrathecal Injection | Intrathecal Ketorolac | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 14 Participants | 30 Participants |
| Age, Continuous | 32.06 years STANDARD_DEVIATION 8.52 | 31.78 years STANDARD_DEVIATION 11.52 | 31.93 years STANDARD_DEVIATION 9.86 |
| Region of Enrollment United States | 16 participants | 14 participants | 30 participants |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 10 Participants | 11 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 14 | 0 / 16 |
| serious Total, serious adverse events | 0 / 14 | 0 / 16 |
Outcome results
Primary
Hyperalgesia
Total Area of hypersensitivity (measured in centimeters) were assessed approximately 24 hours post intrathecal ketorolac injection by the method of using a von Frey filament
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intrathecal Ketorolac | Hyperalgesia | 70.1 centimeters^2 | Standard Deviation 40.5 |
| Placebo Intrathecal Injection | Hyperalgesia | 48.4 centimeters^2 | Standard Deviation 33.5 |
Secondary
Cerebrospinal Fluid (CSF) Prostaglandin E2 (PGE2) Concentration
Concentration of prostaglandin E2 (PGE2) in Cerebrospinal fluid (CSF) 2.5 hours post injection of intrathecal ketorolac
Time frame: 2.5 hours
Population: 11 Subjects in the Intrathecal Ketorolac group received post study treatment analysis of CSF for PGE2. We were not able to obtain CSF samples in 3 of the subjects post study drug injection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intrathecal Ketorolac | Cerebrospinal Fluid (CSF) Prostaglandin E2 (PGE2) Concentration | 87 picograms per milliliter | Standard Deviation 95 |
| Placebo Intrathecal Injection | Cerebrospinal Fluid (CSF) Prostaglandin E2 (PGE2) Concentration | 75 picograms per milliliter | Standard Deviation 41 |