Healthy Volunteer Study
Conditions
Brief summary
The purpose of this study is to determine the effect of intrathecal oxytocin on areas and intensity of hyperalgesia and allodynia induced by topical capsaicin.
Detailed description
Purpose: There is a strong experimental basis to support the study of oxytocin by the spinal route for analgesia in humans. Oxytocin containing cells in the dorsal parvocellular division of the paraventricular nucleus (PVN) project to the spinal cord (1). Noxious stimulation activates these cells via the A1 noradrenergic relay in the pons (2) and produces analgesia by spinal release of oxytocin, since intrathecal injection of an oxytocin receptor antagonist worsens pain behaviors from peripheral inflammation (3). Direct electrical stimulation of the PVN reduces dorsal horn neuronal responses to noxious stimulation, and this is blocked by administration of sequestering antibody for oxytocin (4). Similarly, direct electrical stimulation of the PVN reduces behavioral sensitivity in a model of chronic neuropathic pain, and this effect is blocked by an oxytocin receptor antagonist (5). Intrathecal injection of oxytocin in normal rats reduces dorsal horn neuronal responses to noxious stimuli (6) as well as behavioral responses to noxious thermal (3), mechanical (3), and chemical (7) stimuli. Finally, intrathecal injection of oxytocin in rat models of chronic pain also reduces dorsal horn neuronal responses to sensory stimulation (6) as well as behavioral responses to thermal (5) and mechanical (7) stimuli. Rationale: We anticipate that oxytocin will be effective after spinal injection in humans against chemical induced hypersensitivity states. Objectives: Determine the effect of intrathecal oxytocin on areas and intensity of hyperalgesia and allodynia induced by topical capsaicin.
Interventions
DRUGOxytocin 15 mcg
Oxytocin 15 mcg will be administered spinally
DRUGOxytocin 150 mcg
Oxytocin 150 mcg will be administered spinally
DRUGPlacebo
placebo will be administered spinally
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Randomization is prepared by a statistician not otherwise involved in the study or data analysis and is maintained by the Wake Forest University School of Medicine research pharmacy. Study drug is dispensed by the research pharmacy labelled as Study drug containing normal saline or oxytocin 15 mcg in normal saline or oxytocin 150 mcg in normal saline to indicate the possible contents of the solution, thereby maintaining blind.
Intervention model description
Subjects are randomized into one of 3 groups to receive, in a double-blind manner, intrathecal saline or intrathecal oxytocin, 15 mcg or 150 mcg
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy * weight \< 240 pounds * American Society of Anesthesiology Category 1 or 2
Exclusion criteria
* allergy to oxytocin or lidocaine * allergy to chilli peppers * Females: active gynecological disease such as uterine fibroids or ongoing bleeding * Pregnancy or currently breastfeeding * Females that have delivered a baby within 2 years of study * Taking prescription medications (exception: oral birth control medication)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hyperalgesia | 105 minutes after study drug injection | The area of hyperalgesia after the first skin heating following topical capsaicin. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from Jan 2, 2014 to Oct 9, 2018 within Wake Forest University Health Sciences (WFUHS) and the community using IRB-approved advertisements. Screening for eligibility and informed consent was obtained at the Pain Mechanisms Laboratory Clinical Research Unit of WFUHS.
Participants by arm
| Arm | Count |
|---|---|
| Oxytocin 15 mcg Oxytocin 15 mcg injected spinally
Oxytocin 15 mcg: Oxytocin 15 mcg will be administered spinally | 8 |
| Oxytocin 150 mcg Oxytocin 150 mcg injected spinally
Oxytocin 150 mcg: Oxytocin 150 mcg will be administered spinally | 5 |
| Placebo Preservative free normal saline injected spinally
Placebo: placebo will be administered spinally | 7 |
| Total | 20 |
Baseline characteristics
| Characteristic | Oxytocin 15 mcg | Oxytocin 150 mcg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 34 years STANDARD_DEVIATION 11 | 35 years STANDARD_DEVIATION 9 | 38 years STANDARD_DEVIATION 10 | 36 years STANDARD_DEVIATION 10 |
| Area of hyperalgesia | 0 square centimeters STANDARD_DEVIATION 0 | 0 square centimeters STANDARD_DEVIATION 0 | 0 square centimeters STANDARD_DEVIATION 0 | 0 square centimeters STANDARD_DEVIATION 0 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 5 Participants | 6 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 4 Participants | 7 Participants | 17 Participants |
| Region of Enrollment United States | 8 participants | 5 participants | 7 participants | 20 participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 3 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 5 | 0 / 7 |
| other Total, other adverse events | 0 / 8 | 0 / 5 | 0 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 5 | 0 / 7 |
Outcome results
Primary
Hyperalgesia
The area of hyperalgesia after the first skin heating following topical capsaicin.
Time frame: 105 minutes after study drug injection
Population: Area of hyperalgesia was determined as described in baseline measures 105 min after study drug injection. The sequence of events was study drug injection followed in 30 min by 5 min heating of the skin followed by capsaicin cream application for 30 min, removal of the cream followed in 30 min by 5 min heating of the skin. After this second heating the area of hyperalgesia was measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin 15 mcg | Hyperalgesia | 103 square centimeters | Standard Deviation 55 |
| Oxytocin 150 mcg | Hyperalgesia | 102 square centimeters | Standard Deviation 76 |
| Placebo | Hyperalgesia | 75 square centimeters | Standard Deviation 33 |
Comparison: The null hypothesis was that there would be no difference in area of hyperalgesia 105 minutes after study drug injection among the three groups.p-value: <0.05ANOVA