Chronic Pain
Conditions
Brief summary
This study proposes to evaluate the effects that a dose of oxytocin given by intramuscular (IM) injection (into the muscle) will have on an area of skin that has been exposed to ultraviolet (UV) light. The area of skin exposed to UV light will have a mild sun burn feeling. Sensory testing will be performed on the area of UV burn. The area will be evaluated for sensitivity in 3 methods: touch, vibratory
Detailed description
This protocol aims to provide an estimate of effect size of intramuscular oxytocin on a test of Aβ and of Aδ fiber sensitivity in injured skin following ultraviolet B (UVB) burned skin. For the primary goal - to examine the effects of oxytocin peripheral nerves after tissue injury - the investigators chose the controlled ultraviolet sunburn model. The investigators propose a randomized, blinded, cross over design with treatment with oxytocin one day and placebo on another. Following baseline measures on each of the two study days, participants will receive an intramuscular injection of oxytocin (Pitocin®) in its indicated dose of 10 IU (17 μg) or an equivalent volume of saline. In order to determine the highest frequency that Aβ nerve fibers can respond to, the investigators will use a device that produces an oscillatory / vibratory stimulus which can be used on the hand. Pain threshold to punctate stimulation within the area of irradiation will be determined using calibrated von Frey filaments and an up-down sequential method which efficiently estimates median thresholds. Thermal heat testing will also be performed by the surface of the skin of the forearm or leg is heated to 45°C using a computer controlled thermode for a period of 5 minutes.
Interventions
DRUGOxytocin
10 IU oxytocin (Pitocin) for intramuscular injection
DRUGSaline
1.5 ml preservative free saline for intramuscular injection
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Participant, Investigator and outcomes assessor will be blinded. Research Pharmacist will prepare the study medication administration and hold the randomization.
Intervention model description
Double blinded crossover treatment with oxytocin and placebo (saline)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female \> 18 and \< 60 years of age, * Body Mass Index (BMI) \<40 * Generally in good health as determined by the Principal Investigator based on prior medical history * Normal blood pressure and resting heart rate without medication
Exclusion criteria
* Hypersensitivity, allergy, or significant reaction to any ingredient of Pitocin® * Any disease, diagnosis, or condition (medical or surgical) that, in the opinion of the Principal Investigator, would place the subject at increased risk * Women who are pregnant (positive result for serum pregnancy test at screening visit), women who are currently nursing or lactating, women that have been pregnant within 2 years. * Neuropathy, chronic pain, diabetes mellitus, or taking benzodiazepines or pain medications on a daily basis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Vibration Frequency Detection Threshold (When Vibration is First Felt) After IM Injection | From 5 minutes to 120 minutes | Vibration frequency detection threshold in the burned area after IM Oxytocin or placebo injection will be obtained by the subject placing the forearm area that was exposed to the UV burn on the oscillatory device and informing the investigators when the first perception of vibration is felt. A recording of the frequency (1 kilo Hertz to 1 Hertz) will be documented. |
| Change in Pain Threshold (the Point Where Pain is First Perceived) to a Punctate Mechanical Stimulus After IM Injection. | From 5 minutes to 120 minutes | Verbal pain punctate stimulus detection threshold (the point where pain is first perceived) in the burned area after IM Oxytocin or Placebo injection will be obtained by using von Frey filaments (small filaments that are similar to a paint brush bristle). The skin will be touched with the filaments and the participant will state when pain is perceived and the size of the filament will be documented. |
| Change in Hypersensitivity to Von Frey Filament (225 milliNewton) After IM Injection. | From 5 minutes to 65 minutes | Hypersensitivity in the burned area after IM Oxytocin or placebo injection will be obtained by using a von Frey filament (small filament that is similar to a paint brush bristle). The skin will be touched with the filament and the participant will state when sensitivity is perceived and the area marked and measured in centimeters squared. |
| Change in Vibration Frequency Detection of Fixed Frequency (When Vibration is First Felt) After IM Injection | From 5 minutes to 65 minutes | Vibration frequency detection of a fixed frequency (256 Hertz) in the burned area after IM Oxytocin or placebo injection will be obtained. The subject will place the wrist area that was exposed to the UV burn on the oscillatory device, the fixed vibratory frequency will begin and will be increased in intensity and the subject will inform the investigators when the first perception of vibration is felt. A recording of the intensity level will be documented in Hertz. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sustained Heat After IM Injection | From 36 minutes to 40 minutes | Verbal pain scores (0 to 10; 0 is equivalent to no pain and 10 is equivalent to the worst pain imaginable) to 40 degree Celsius temperature applied to the site of the UV burn after IM Oxytocin or placebo injection. |
| Change in Sustained Heat After IM Oxytocin or Placebo Injection (Lower Leg) | From 21 minutes to 65 minutes | Verbal pain scores (0 to 10; 0 is equivalent to no pain and 10 is equivalent to the worst pain imaginable) to 45 degree Celsius temperature applied to the calf (lower leg) after IM Oxytocin or placebo injection. |
| Change in Sustained Heat After IM Injection Non Dominant Arm | From 21 minutes to 125 minutes | Verbal pain scores (0 to 10; 0 is equivalent to no pain and 10 is equivalent to the worst pain imaginable) to 45 degree Celsius temperature after IM Oxytocin or placebo injection. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oxytocin First, Then Saline Placebo Intramuscular injection of oxytocin (Pitocin®), 10 IU on the first study day and of 1 ml saline placebo on the second study day
Oxytocin: 10 IU oxytocin (Pitocin) for intramuscular injection
Saline: 1.5 ml preservative free saline for intramuscular injection | 5 |
| Saline Placebo First, Then Oxytocin Intramuscular injection of 1 ml saline placebo on the second study day and of oxytocin (Pitocin®), 10 IU on the second study day
Oxytocin: 10 IU oxytocin (Pitocin) for intramuscular injection
Saline: 1.5 ml preservative free saline for intramuscular injection | 5 |
| Total | 10 |
Baseline characteristics
| Characteristic | Oxytocin First, Then Saline Placebo | Saline Placebo First, Then Oxytocin | 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 | 5 Participants | 5 Participants | 10 Participants |
| Age, Continuous | 36 years STANDARD_DEVIATION 12 | 40 years STANDARD_DEVIATION 12 | 38 years STANDARD_DEVIATION 11 |
| Body Mass Index | 29 kg/m^2 STANDARD_DEVIATION 5 | 26 kg/m^2 STANDARD_DEVIATION 3 | 27 kg/m^2 STANDARD_DEVIATION 4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 10 Participants |
| Region of Enrollment United States | 5 participants | 5 participants | 10 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Change in Hypersensitivity to Von Frey Filament (225 milliNewton) After IM Injection.
Hypersensitivity in the burned area after IM Oxytocin or placebo injection will be obtained by using a von Frey filament (small filament that is similar to a paint brush bristle). The skin will be touched with the filament and the participant will state when sensitivity is perceived and the area marked and measured in centimeters squared.
Time frame: From 5 minutes to 65 minutes
Population: Please note that the protocol was amended after the first 5 participants. The first 5 participants were tested for pain THRESHOLD to mechanical stimulation and the last 5 participants were tested for degree of pain INTENSITY to a fixed mechanical stimulation. This outcome relates to the last 5 participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Change in Hypersensitivity to Von Frey Filament (225 milliNewton) After IM Injection. | 6.4 cm^2 | Standard Deviation 8.6 |
| Placebo | Change in Hypersensitivity to Von Frey Filament (225 milliNewton) After IM Injection. | 8.8 cm^2 | Standard Deviation 8.6 |
Comparison: Exploratory analysis without power calculationp-value: 0.79ANOVA
Primary
Change in Pain Threshold (the Point Where Pain is First Perceived) to a Punctate Mechanical Stimulus After IM Injection.
Verbal pain punctate stimulus detection threshold (the point where pain is first perceived) in the burned area after IM Oxytocin or Placebo injection will be obtained by using von Frey filaments (small filaments that are similar to a paint brush bristle). The skin will be touched with the filaments and the participant will state when pain is perceived and the size of the filament will be documented.
Time frame: From 5 minutes to 120 minutes
Population: Please note that the protocol was amended after the first 5 participants. The first 5 participants were tested for pain THRESHOLD to mechanical stimulation and the last 5 participants were tested for degree of pain INTENSITY to a fixed mechanical stimulation. This outcome relates to the first 5 participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Change in Pain Threshold (the Point Where Pain is First Perceived) to a Punctate Mechanical Stimulus After IM Injection. | 0.20 grams | Standard Deviation 0.66 |
| Placebo | Change in Pain Threshold (the Point Where Pain is First Perceived) to a Punctate Mechanical Stimulus After IM Injection. | 0.29 grams | Standard Deviation 0.55 |
Comparison: Exploratory analysis without power calculationp-value: 0.92ANOVA
Primary
Change in Vibration Frequency Detection of Fixed Frequency (When Vibration is First Felt) After IM Injection
Vibration frequency detection of a fixed frequency (256 Hertz) in the burned area after IM Oxytocin or placebo injection will be obtained. The subject will place the wrist area that was exposed to the UV burn on the oscillatory device, the fixed vibratory frequency will begin and will be increased in intensity and the subject will inform the investigators when the first perception of vibration is felt. A recording of the intensity level will be documented in Hertz.
Time frame: From 5 minutes to 65 minutes
Population: Please note that the protocol was amended after the first 5 participants. The first 5 participants were tested for vibration FREQUENCY detection threshold and the last 5 participants were tested for vibration INTENSITY detection threshold. This outcome relates to the last 5 participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Change in Vibration Frequency Detection of Fixed Frequency (When Vibration is First Felt) After IM Injection | 1.8 Hz | Standard Deviation 1.4 |
| Placebo | Change in Vibration Frequency Detection of Fixed Frequency (When Vibration is First Felt) After IM Injection | 1.7 Hz | Standard Deviation 3.9 |
p-value: 0.93ANOVA
Primary
Change in Vibration Frequency Detection Threshold (When Vibration is First Felt) After IM Injection
Vibration frequency detection threshold in the burned area after IM Oxytocin or placebo injection will be obtained by the subject placing the forearm area that was exposed to the UV burn on the oscillatory device and informing the investigators when the first perception of vibration is felt. A recording of the frequency (1 kilo Hertz to 1 Hertz) will be documented.
Time frame: From 5 minutes to 120 minutes
Population: Please note that the protocol was amended after the first 5 participants. The first 5 participants were tested for vibration FREQUENCY detection threshold and the last 5 participants were tested for vibration INTENSITY detection threshold. This outcome relates to the first 5 participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Change in Vibration Frequency Detection Threshold (When Vibration is First Felt) After IM Injection | 22 Hz | Standard Deviation 14 |
| Placebo | Change in Vibration Frequency Detection Threshold (When Vibration is First Felt) After IM Injection | 21 Hz | Standard Deviation 8 |
Comparison: Exploratory analysis without power calculationp-value: 0.83ANOVA
Secondary
Change in Sustained Heat After IM Injection
Verbal pain scores (0 to 10; 0 is equivalent to no pain and 10 is equivalent to the worst pain imaginable) to 40 degree Celsius temperature applied to the site of the UV burn after IM Oxytocin or placebo injection.
Time frame: From 36 minutes to 40 minutes
Population: Please note that the protocol was amended after the first 5 participants. Only the last 5 participants were tested for pain report to sustain heat applied at the site of the UV-B burn.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Change in Sustained Heat After IM Injection | 0.10 score on a scale | Standard Deviation 0.22 |
| Placebo | Change in Sustained Heat After IM Injection | -0.20 score on a scale | Standard Deviation 0.45 |
p-value: 0.83ANOVA
Secondary
Change in Sustained Heat After IM Injection Non Dominant Arm
Verbal pain scores (0 to 10; 0 is equivalent to no pain and 10 is equivalent to the worst pain imaginable) to 45 degree Celsius temperature after IM Oxytocin or placebo injection.
Time frame: From 21 minutes to 125 minutes
Population: Please note that the protocol was amended after the first 5 participants. The first 5 participants were tested for pain report to sustained heat applied to the ARM and the last 5 participants were tested for pain report to sustained heat applied to the LEG. This outcome relates to the first 5 participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Change in Sustained Heat After IM Injection Non Dominant Arm | -0.30 units on a scale | Standard Deviation 0.65 |
| Placebo | Change in Sustained Heat After IM Injection Non Dominant Arm | -0.70 units on a scale | Standard Deviation 0.84 |
p-value: 0.89ANOVA
Secondary
Change in Sustained Heat After IM Oxytocin or Placebo Injection (Lower Leg)
Verbal pain scores (0 to 10; 0 is equivalent to no pain and 10 is equivalent to the worst pain imaginable) to 45 degree Celsius temperature applied to the calf (lower leg) after IM Oxytocin or placebo injection.
Time frame: From 21 minutes to 65 minutes
Population: Please note that the protocol was amended after the first 5 participants. The first 5 participants were tested for pain report to sustained heat applied to the ARM and the last 5 participants were tested for pain report to sustained heat applied to the LEG. This outcome relates to the last 5 participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Change in Sustained Heat After IM Oxytocin or Placebo Injection (Lower Leg) | -0.55 score on a scale | Standard Deviation 0.94 |
| Placebo | Change in Sustained Heat After IM Oxytocin or Placebo Injection (Lower Leg) | 0.10 score on a scale | Standard Deviation 0.55 |
p-value: 0.57ANOVA