The Effect of Intranasal Oxytocin on Pain Sensitivity and Threshold

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02550093
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 19.1
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

Oxytocin is neurohypophysial peptide that acts mainly as a neuromodulator in the brain.The vast majority of basic science studies suggested a large effect of oxytocin in minimizing acute pain.Few studies have demonstrated an association between plasma levels of oxytocin and pain in humans. Since addictive properties of oxytocin have not been described, the drug may have important application in the management of acute and chronic pain. No studies have examined the effect of intranasal oxytocin on pain sensitivity and threshold.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Procedure: Intervention 1; Behavioral: Washout Period; Procedure: Intervention 2	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effect of Intranasal Oxytocin on Pain Sensitivity and Threshold: A Randomized, Double Blinded, Crossover Volunteer Study
• Study Start Date: Apr 1, 2015
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oxytocin, then Normal Saline Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing on intervention 1 (day 1). Following a wash-out period of 13 days the same subject will then receive a nasal spray(s) into each nostril of 4 Units up to 32 units of Normal Saline prior to Thermal Evaluation System Testing on intervention 2 (day 14).	Procedure: Intervention 1; Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing on intervention 1 (Day 1).; Other Names: Day 1 ; Behavioral: Washout Period; The wash-out period will be between intervention 1 and intervention 2. 13 days in length.; Procedure: Intervention 2; Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing on intervention 2 (Day 14).; Other Names: Day 14
Experimental: Normal Saline, then Oxytocin Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Normal Saline prior to Thermal Evaluation System Testing on intervention 1 (day 1). Following a wash-out period of 14 to 15 days the same subject will then receive nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing on intervention 2 (day 14).	Procedure: Intervention 1; Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing on intervention 1 (Day 1).; Other Names: Day 1 ; Behavioral: Washout Period; The wash-out period will be between intervention 1 and intervention 2. 13 days in length.; Procedure: Intervention 2; Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing on intervention 2 (Day 14).; Other Names: Day 14

Outcome Measures

Primary Outcome Measures

1. Hot and Cold Thermal Sensory Threshold for Pain at Baseline in Degrees Celsius. [Baseline]

   Thermal Sensory Threshold for Pain at baseline prior to study drug administration. Evaluation of subjects baseline responses of perception of hot and cold stimuli utilizing the Medoc Pathway Pain &Sensory Evaluation System (Medoc Ltd, Israel). The baseline response variable was estimated by averaging the subjects response over three trials, with an interval of 30 seconds. A thermode was attached to the subjects hand and the subject was asked to press a mouse button when they perceive the sensation of heat pain or cold pain. The temperature range was 51C to 0C.

2. Hot and Cold Thermal Sensory Threshold for Pain at 45 Minutes in Degrees Celsius. [45 minutes]

   Thermal Sensory Threshold for Pain at 45 minutes after study drug administration. Evaluation of subjects responses of perception of hot and cold stimuli utilizing the Medoc Pathway Pain &Sensory Evaluation System (Medoc Ltd, Israel). The response variable was estimated by averaging the subjects response over three trials, with an interval of 30 seconds. A thermode was attached to the subjects hand and the subject was asked to press a mouse button when they perceive the sensation of heat pain or cold pain. The temperature range was 51C to 0C.

3. Hot and Cold Thermal Sensory Threshold for Pain at 90 Minutes in Degrees Celsius. [90 minutes]

   Thermal Sensory Threshold for Pain at 90 minutes after study drug administration. Evaluation of subjects responses of perception of hot and cold stimuli utilizing the Medoc Pathway Pain &Sensory Evaluation System (Medoc Ltd, Israel). The response variable was estimated by averaging the subjects response over three trials, with an interval of 30 seconds. A thermode was attached to the subjects hand and the subject was asked to press a mouse button when they perceive the sensation of heat pain or cold pain. The temperature range was 51C to 0C.

4. Mechanical Pain Threshold for Pain at Baseline in Grams. [Baseline]

   Mechanical pain threshold for pain at baseline utilizing a digital electrovonfrey anesthesiometer (IITC model Alemo 2290-4; Woodland Hills, CA, USA). The subjects response to painful stimulus was recorded in grams. Each variable was estimated by averaging a participant's responses over 3 trials, with an intertrial interval of 30 s. The lower amount in grams the more sensitive you are to pain.

5. Mechanical Pain Threshold for Pain at 45 Minutes in Grams. [45 minutes]

   Mechanical pain threshold for pain at 45 minutes utilizing a digital electrovonfrey anesthesiometer (IITC model Alemo 2290-4; Woodland Hills, CA, USA). The subjects response to painful stimulus was recorded in grams. Each variable was estimated by averaging a participant's responses over 3 trials, with an intertrial interval of 30 s. The lower amount in grams the more sensitive you are to pain.

6. Mechanical Pain Threshold for Pain at 90 Minutes in Grams. [90 minutes]

   Mechanical pain threshold for pain at 90 minutes utilizing a digital electrovonfrey anesthesiometer (IITC model Alemo 2290-4; Woodland Hills, CA, USA). The subjects response to painful stimulus was recorded in grams. Each variable was estimated by averaging a participant's responses over 3 trials, with an intertrial interval of 30 s. The lower amount in grams the more sensitive you are to pain.

7. Suprathreshold Magnitude for Pain at Baseline Measured in Visual Analog Pain Scores. [Baseline]

   Supra-threshold magnitude for pain was assessed utilizing the Medoc Pathway System with contact heat evoked potential simulator at 49 degrees Celsius. Visual analog pain score ranges from 0 (no pain) to 10 (worst pain imaginable).

8. Suprathreshold Magnitude for Pain at 45 Minutes Measured in Visual Analog Pain Scores. [45 minutes]

   Supra-threshold magnitude for pain was assessed utilizing the Medoc Pathway System with contact heat evoked potential simulator at 49 degrees Celsius. Visual analog pain score ranges from 0 (no pain) to 10 (worst pain imaginable).

9. Suprathreshold Magnitude for Pain at 90 Minutes Measured in Visual Analog Pain Scores. [90 minutes]

   Supra-threshold magnitude for pain was assessed utilizing the Medoc Pathway System with contact heat evoked potential simulator at 49 degrees Celsius. Visual analog pain score ranges from 0 (no pain) to 10 (worst pain imaginable).

10. Thermal Wind-up Pain Assessment at Baseline [Baseline]

    Using a Visual Analog Scale (VAS) subjects will be asked to rate the painfulness of the stimulus for thermal wind-up pain utilizing the medoc pathway system. Each VAS score was recorded over 10 trials, with an interval of 3s. The average VAS score was reported. Visual analog scale ranges from 0 (no pain) to 10 (worst pain imaginable).

11. Thermal Wind-up Pain at 45 Minutes [45 minutes]

    Using a Visual Analog Scale (VAS) subjects will be asked to rate the painfulness of the stimulus for thermal wind-up pain utilizing the medoc pathway system. Each VAS score was recorded over 10 trials, with an interval of 3s. The average VAS score was reported. Visual analog scale ranges from 0 (no pain) to 10 (worst pain imaginable).

12. Thermal Wind-up Pain at 90 Minutes [90 minutes]

    Using a Visual Analog Scale (VAS) subjects will be asked to rate the painfulness of the stimulus for thermal wind-up pain utilizing the medoc pathway system. Each VAS score was recorded over 10 trials, with an interval of 3s. The average VAS score was reported. Visual analog scale ranges from 0 (no pain) to 10 (worst pain imaginable).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 35 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy males and females volunteers, English speaking

Exclusion Criteria:

• Pregnancy, lactation, allergy to preservatives, mental disease, any chronic pain and any current use of analgesics, anxiety or depression.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University Feinberg School of Medicine	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University

Investigators

• Principal Investigator: David R Walega, MD, Northwestern University Feinberg School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

• Fewtrell MS, Loh KL, Blake A, Ridout DA, Hawdon J. Randomised, double blind trial of oxytocin nasal spray in mothers expressing breast milk for preterm infants. Arch Dis Child Fetal Neonatal Ed. 2006 May;91(3):F169-74. Epub 2005 Oct 13.
• MacDonald E, Dadds MR, Brennan JL, Williams K, Levy F, Cauchi AJ. A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research. Psychoneuroendocrinology. 2011 Sep;36(8):1114-26. doi: 10.1016/j.psyneuen.2011.02.015. Epub 2011 Mar 23. Review.
• Rash JA, Aguirre-Camacho A, Campbell TS. Oxytocin and pain: a systematic review and synthesis of findings. Clin J Pain. 2014 May;30(5):453-62. doi: 10.1097/AJP.0b013e31829f57df. Review.
• Singer T, Snozzi R, Bird G, Petrovic P, Silani G, Heinrichs M, Dolan RJ. Effects of oxytocin and prosocial behavior on brain responses to direct and vicariously experienced pain. Emotion. 2008 Dec;8(6):781-91. doi: 10.1037/a0014195.
• Wang YL, Yuan Y, Yang J, Wang CH, Pan YJ, Lu L, Wu YQ, Wang DX, Lv LX, Li RR, Xue L, Wang XH, Bi JW, Liu XF, Qian YN, Deng ZK, Zhang ZJ, Zhai XH, Zhou XJ, Wang GL, Zhai JX, Liu WY. The interaction between the oxytocin and pain modulation in headache patients. Neuropeptides. 2013 Apr;47(2):93-7. doi: 10.1016/j.npep.2012.12.003. Epub 2013 Jan 30.
• Yamasue H, Yee JR, Hurlemann R, Rilling JK, Chen FS, Meyer-Lindenberg A, Tost H. Integrative approaches utilizing oxytocin to enhance prosocial behavior: from animal and human social behavior to autistic social dysfunction. J Neurosci. 2012 Oct 10;32(41):14109-17. doi: 10.1523/JNEUROSCI.3327-12.2012. Review.

• Responsible Party: David Walega, Associate Professor, Chief, Division of Pain Medicine, Northwestern University
• ClinicalTrials.gov Identifier: NCT02550093
• Other Study ID Numbers: STU86297
• First Posted: Sep 15, 2015
• Last Update Posted: May 16, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by David Walega, Associate Professor, Chief, Division of Pain Medicine, Northwestern University: Volunteers
• Additional relevant MeSH terms: Hypersensitivity

Study Results

Participant Flow

Recruitment Details	Cross-over study design

Arm/Group Title	Oxytocin, Then Normal Saline	Normal Saline, Then Oxytocin
Arm/Group Description	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing on intervention 1 (day 1). Following a wash-out period of 13 days the same subject will then receive a nasal spray(s) into each nostril of 4 Units up to 32 units of Normal Saline prior to Thermal Evaluation System Testing on intervention 2 (day 14).	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Normal Saline prior to Thermal Evaluation System Testing on intervention 1 (day 1). Following a wash-out period of 14 to 15 days the same subject will then receive nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing on intervention 2 (day 14).
Period Title: Intervention 1
STARTED	10	10
COMPLETED	10	10
NOT COMPLETED	0	0
Period Title: Intervention 1
STARTED	10	10
COMPLETED	10	10
NOT COMPLETED	0	0
Period Title: Intervention 1
STARTED	10	10
COMPLETED	10	10
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of either Oxytocin then Normal Saline or Normal Saline then Oxytocin prior to Thermal Evaluation System Testing.
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	20 100%
>=65 years	0 0%
Age (Years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Years]	24
Sex: Female, Male (Count of Participants)
Female	12 60%
Male	8 40%

Outcome Measures

1. Primary Outcome

Title	Hot and Cold Thermal Sensory Threshold for Pain at Baseline in Degrees Celsius.
Description	Thermal Sensory Threshold for Pain at baseline prior to study drug administration. Evaluation of subjects baseline responses of perception of hot and cold stimuli utilizing the Medoc Pathway Pain &Sensory Evaluation System (Medoc Ltd, Israel). The baseline response variable was estimated by averaging the subjects response over three trials, with an interval of 30 seconds. A thermode was attached to the subjects hand and the subject was asked to press a mouse button when they perceive the sensation of heat pain or cold pain. The temperature range was 51C to 0C.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxytocin	Normal Saline
Arm/Group Description	Baseline recording - no study drug administerd prior to Thermal Evaluation System Testing.	Baseline recording - no study drug administerd prior to Thermal Evaluation System Testing.
Measure Participants	20	20
Heat	43.93 (4.18)	43.0 (4.34)
Cold	14.81 (11.10)	13.33 (10.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxytocin, Normal Saline
	Comments	HEAT
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	.47
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oxytocin, Normal Saline
	Comments	COLD
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	Hot and Cold Thermal Sensory Threshold for Pain at 45 Minutes in Degrees Celsius.
Description	Thermal Sensory Threshold for Pain at 45 minutes after study drug administration. Evaluation of subjects responses of perception of hot and cold stimuli utilizing the Medoc Pathway Pain &Sensory Evaluation System (Medoc Ltd, Israel). The response variable was estimated by averaging the subjects response over three trials, with an interval of 30 seconds. A thermode was attached to the subjects hand and the subject was asked to press a mouse button when they perceive the sensation of heat pain or cold pain. The temperature range was 51C to 0C.
Time Frame	45 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxytocin	Normal Saline
Arm/Group Description	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing. Oxytocin: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Normal Saline prior to Thermal Evaluation System Testing. Normal Saline: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.
Measure Participants	20	20
Heat	43.60 (3.68)	43.42 (3.98)
Cold	15.68 (10.60)	15.17 (10.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxytocin, Normal Saline
	Comments	HEAT
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.84
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oxytocin, Normal Saline
	Comments	COLD
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Primary Outcome

Title	Hot and Cold Thermal Sensory Threshold for Pain at 90 Minutes in Degrees Celsius.
Description	Thermal Sensory Threshold for Pain at 90 minutes after study drug administration. Evaluation of subjects responses of perception of hot and cold stimuli utilizing the Medoc Pathway Pain &Sensory Evaluation System (Medoc Ltd, Israel). The response variable was estimated by averaging the subjects response over three trials, with an interval of 30 seconds. A thermode was attached to the subjects hand and the subject was asked to press a mouse button when they perceive the sensation of heat pain or cold pain. The temperature range was 51C to 0C.
Time Frame	90 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxytocin	Normal Saline
Arm/Group Description	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing. Oxytocin: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Normal Saline prior to Thermal Evaluation System Testing. Normal Saline: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.
Measure Participants	20	20
Heat	43.94 (3.97)	43.95 (3.80)
Cold	15.41 (11.24)	12.96 (11.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxytocin, Normal Saline
	Comments	HEAT
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.92
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oxytocin, Normal Saline
	Comments	COLD
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Primary Outcome

Title	Mechanical Pain Threshold for Pain at Baseline in Grams.
Description	Mechanical pain threshold for pain at baseline utilizing a digital electrovonfrey anesthesiometer (IITC model Alemo 2290-4; Woodland Hills, CA, USA). The subjects response to painful stimulus was recorded in grams. Each variable was estimated by averaging a participant's responses over 3 trials, with an intertrial interval of 30 s. The lower amount in grams the more sensitive you are to pain.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxytocin	Normal Saline
Arm/Group Description	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing. Oxytocin: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Normal Saline prior to Thermal Evaluation System Testing. Normal Saline: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.
Measure Participants	20	20
Mean (Standard Deviation) [Grams]	194.90 (117.52)	223.31 (149.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxytocin, Normal Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.60
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Primary Outcome

Title	Mechanical Pain Threshold for Pain at 45 Minutes in Grams.
Description	Mechanical pain threshold for pain at 45 minutes utilizing a digital electrovonfrey anesthesiometer (IITC model Alemo 2290-4; Woodland Hills, CA, USA). The subjects response to painful stimulus was recorded in grams. Each variable was estimated by averaging a participant's responses over 3 trials, with an intertrial interval of 30 s. The lower amount in grams the more sensitive you are to pain.
Time Frame	45 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxytocin	Normal Saline
Arm/Group Description	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing. Oxytocin: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Normal Saline prior to Thermal Evaluation System Testing. Normal Saline: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.
Measure Participants	20	20
Mean (Standard Deviation) [Grams]	195.07 (145.41)	197.49 (124.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxytocin, Normal Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.68
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Primary Outcome

Title	Mechanical Pain Threshold for Pain at 90 Minutes in Grams.
Description	Mechanical pain threshold for pain at 90 minutes utilizing a digital electrovonfrey anesthesiometer (IITC model Alemo 2290-4; Woodland Hills, CA, USA). The subjects response to painful stimulus was recorded in grams. Each variable was estimated by averaging a participant's responses over 3 trials, with an intertrial interval of 30 s. The lower amount in grams the more sensitive you are to pain.
Time Frame	90 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxytocin	Normal Saline
Arm/Group Description	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing. Oxytocin: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Normal Saline prior to Thermal Evaluation System Testing. Normal Saline: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.
Measure Participants	20	20
Mean (Standard Deviation) [Grams]	198.76 (141.41)	208.77 (124.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxytocin, Normal Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Primary Outcome

Title	Suprathreshold Magnitude for Pain at Baseline Measured in Visual Analog Pain Scores.
Description	Supra-threshold magnitude for pain was assessed utilizing the Medoc Pathway System with contact heat evoked potential simulator at 49 degrees Celsius. Visual analog pain score ranges from 0 (no pain) to 10 (worst pain imaginable).
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxytocin	Normal Saline
Arm/Group Description	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing. Oxytocin: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Normal Saline prior to Thermal Evaluation System Testing. Normal Saline: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.
Measure Participants	20	20
Mean (Standard Deviation) [scores on a scale]	2.90 (1.65)	3.02 (1.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxytocin, Normal Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.97
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Primary Outcome

Title	Suprathreshold Magnitude for Pain at 45 Minutes Measured in Visual Analog Pain Scores.
Description	Supra-threshold magnitude for pain was assessed utilizing the Medoc Pathway System with contact heat evoked potential simulator at 49 degrees Celsius. Visual analog pain score ranges from 0 (no pain) to 10 (worst pain imaginable).
Time Frame	45 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxytocin	Normal Saline
Arm/Group Description	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing. Oxytocin: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Normal Saline prior to Thermal Evaluation System Testing. Normal Saline: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.
Measure Participants	20	20
Mean (Standard Deviation) [scores on a scale]	2.58 (1.37)	2.67 (1.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxytocin, Normal Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.97
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

9. Primary Outcome

Title	Suprathreshold Magnitude for Pain at 90 Minutes Measured in Visual Analog Pain Scores.
Description	Supra-threshold magnitude for pain was assessed utilizing the Medoc Pathway System with contact heat evoked potential simulator at 49 degrees Celsius. Visual analog pain score ranges from 0 (no pain) to 10 (worst pain imaginable).
Time Frame	90 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxytocin	Normal Saline
Arm/Group Description	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing. Oxytocin: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Normal Saline prior to Thermal Evaluation System Testing. Normal Saline: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.
Measure Participants	20	20
Mean (Standard Deviation) [scores on a scale]	2.53 (1.58)	2.29 (1.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxytocin, Normal Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.61
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

10. Primary Outcome

Title	Thermal Wind-up Pain Assessment at Baseline
Description	Using a Visual Analog Scale (VAS) subjects will be asked to rate the painfulness of the stimulus for thermal wind-up pain utilizing the medoc pathway system. Each VAS score was recorded over 10 trials, with an interval of 3s. The average VAS score was reported. Visual analog scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxytocin	Normal Saline
Arm/Group Description	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing. Oxytocin: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Normal Saline prior to Thermal Evaluation System Testing. Normal Saline: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.
Measure Participants	20	20
Mean (Standard Deviation) [scores on a scale]	3.59 (2.09)	3.15 (1.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxytocin, Normal Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

11. Primary Outcome

Title	Thermal Wind-up Pain at 45 Minutes
Description	Using a Visual Analog Scale (VAS) subjects will be asked to rate the painfulness of the stimulus for thermal wind-up pain utilizing the medoc pathway system. Each VAS score was recorded over 10 trials, with an interval of 3s. The average VAS score was reported. Visual analog scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Time Frame	45 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxytocin	Normal Saline
Arm/Group Description	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing. Oxytocin: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Normal Saline prior to Thermal Evaluation System Testing. Normal Saline: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.
Measure Participants	20	20
Mean (Standard Deviation) [scores on a scale]	2.99 (1.71)	2.85 (1.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxytocin, Normal Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

12. Primary Outcome

Title	Thermal Wind-up Pain at 90 Minutes
Description	Using a Visual Analog Scale (VAS) subjects will be asked to rate the painfulness of the stimulus for thermal wind-up pain utilizing the medoc pathway system. Each VAS score was recorded over 10 trials, with an interval of 3s. The average VAS score was reported. Visual analog scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Time Frame	90 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxytocin	Normal Saline
Arm/Group Description	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing. Oxytocin: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.	Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of Normal Saline prior to Thermal Evaluation System Testing. Normal Saline: Each subject will receive nasal spray(s) into each nostril of 4 Units up to 32 units of study drug prior to Thermal Evaluation System Testing.
Measure Participants	20	20
Mean (Standard Deviation) [scores on a scale]	2.82 (1.63)	2.63 (1.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxytocin, Normal Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.75
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	24hrs after intervention.
Adverse Event Reporting Description	Assessments completed 24 hours after participants who completed study interventions.
Arm/Group Title	Oxytocin		Normal Saline
Arm/Group Description	Subjects received nasal spray(s) into each nostril of 4 Units up to 32 units of Oxytocin prior to Thermal Evaluation System Testing.		Subjects received nasal spray(s) into each nostril of Normal Saline prior to Thermal Evaluation System Testing.
All Cause Mortality
	Oxytocin		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Serious Adverse Events
	Oxytocin		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Oxytocin		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)

Limitations/Caveats

Though we used the same method of intranasal administration as preceding studies, it is possible that the oxytocin did not reach peak levels at the time of the testing or was not absorbed. We did not assess plasma levels of oxytocin to assess whether absorption occurred and was consistent among all participants.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.