Efficacy of Spinal Oxytocin in Healthy Volunteers

Study Overview
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Brief Summary
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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
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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.

Official Title
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Efficacy of Intrathecal Oxytocin in Human Volunteers

Conditions
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Healthy Volunteer Study

Intervention / Treatment
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* Drug: Oxytocin 15 mcg
* Drug: Oxytocin 150 mcg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxytocin 15 mcg<br>Oxytocin 15 mcg injected spinally | Drug: Oxytocin 15 mcg<br>* Oxytocin 15 mcg will be administered spinally<br>|
| Experimental: Oxytocin 150 mcg<br>Oxytocin 150 mcg injected spinally | Drug: Oxytocin 150 mcg<br>* Oxytocin 150 mcg will be administered spinally<br>|
| Active Comparator: Placebo<br>Preservative free normal saline injected spinally | Drug: Placebo<br>* placebo will be administered spinally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hyperalgesia | The area of hyperalgesia after the first skin heating following topical capsaicin. | 105 minutes after study drug injection |