Vasopressin and Pain Perception in the Brain

NCT03446456 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 1 other identifier: HP-00076723
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The feeling of pain is not just a sensory experience, but is also influenced by emotions, beliefs and expectations, making pain a highly subjective experience. This is evident in clinical practice, where the behavior of the physician and the treatment context can strongly influence the pain experience of patients. Research has shown that patients' expectation that a treatment will reduce pain influences individual perception of pain, even if the treatment has no active ingredient. The expectancy-induced analgesia emerges due to a modulation of the individual pain experience of patients by an engagement of endogenous inhibitory systems in the central nervous system. The development of expectancy-induced analgesia can be generated in several ways. The investigators have previously demonstrated that social information and observational learning (e.g. the patient observes analgesia in another person receiving a treatment) can lead to expectancy-induced analgesia and pain reduction. However, the neural mechanisms (mechanisms in the brain) of how these expectancies are acquired and the neural mechanisms of analgesia induced by observational learning are unknown. The investigators recently established a procedure to investigate neural mechanisms of observational learning in placebo analgesia. Here the investigators propose to investigate the influence of vasopressin, a neurotransmitter that is important for social interaction, on observational learning. The investigators will use functional magnetic resonance imaging (fMRI), a non-invasive method, to investigate neural activity in humans. Participants will either receive vasopressin or saline with a nasal spray. During fMRI scanning, participants will then undergo an observational learning phase, where the study participants will learn the experience of analgesia in another person through a video, and a testing phase, where participants will perceive painful stimulations with the same cues as the observational phase. The comparison of the vasopressin group and the saline group will allow us to investigate how vasopressin influences behavioral effects of observational learning on pain perception as well as its effect on the neural processing of observational learning. A better understanding of how the human brain processes observationally-induced analgesia would allow us to improve the therapeutic context of pain treatments by increasing the contextual factors which help patients cope with pain.

Conditions

Acute Pain

Keywords

Magnetic Resonance Imaging; Healthy Volunteers; Arginine Vasopressin; Antidiuretic Hormone; Analgesia; Social Behavior

Outcome Measures

Primary Outcomes (1)

• Change in BOLD Singal in Supplementary Motor Area Compared to Whole Brain Average During the Painful Stimulation

  Blood oxygenation level dependent (BOLD) responses will allow the identification of relative activation/deactivation in the brain as a result of events (e.g. painful stimulations) that will be given during the experiment. Changes in the Percentage of BOLD signal are calculated as the BOLD signal in the right supplementary motor area during the 20-second heat pain divided by the whole-brain average BOLD signal during that 20-second heat pain.

  Day 2, the average of 24 trials of painful stimulations with each stimulation lasting 20 seconds

Secondary Outcomes (2)

• Heating Temperature

  Day 1 (calibration)

• Pain Ratings

  Day 2 (test)

Other Outcomes (1)

• Implicit Association Test (IAT) Response Latency Difference

  Day 1

Study Arms (2)

Saline

PLACEBO COMPARATOR

Under direction of a research team member, participants will self-administer intranasal normal saline shortly before beginning the fMRI experiment. Investigators, staff, and participants were blinded to the treatment options. Each of the agents will be administrated by means of a nasal spray. Participants will be instructed by a nurse/PI to self-administer the nasal spray as follows: one spray in each nostril alternating sides, 30 seconds apart for a total of two sprays per nostril.

Other: Saline; Behavioral: Observational learning; Other: fMRI data aquisition

Arginine vasopressin

EXPERIMENTAL

Under direction of a research team member, participants will self-administer intranasal vasopressin shortly before beginning the fMRI experiment. The of AVP will be 40IU. The quantity per unit (1 mL) of Arg8-vasopressin synthetic, manufactured by Polypeptide Group Inc. (http://www.polypeptide.com) was 0.323 mg. This amount was diluted in 0.9% sodium chloride (B. Broun Medical Inc.).

Drug: Arginine vasopressin; Behavioral: Observational learning; Other: fMRI data aquisition

Interventions

Arginine vasopressin DRUG

Intranasal vasopressin will be administered shortly before the fMRI experiment.

Also known as: Arg8-vasopressin synthetic

Arginine vasopressin

Saline OTHER

Intranasal saline will serve as a placebo for participants in the Saline Arm

Also known as: Placebo

Saline

Observational learning BEHAVIORAL

During the observational learning intervention, participants will learn the experience of analgesia in another person via a video. Participants will learn the analgesia nature of the placebo cream and the neutral nature of the control cream.

Also known as: Social observation

Arginine vasopressin; Saline

fMRI data aquisition OTHER

All participants from the intranasal vasopressin and intranasal saline groups will go through a fMRI data acquisition to obtain the brain structural, brain resting-states and functional MRI scans.

Arginine vasopressin; Saline

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ( 18-55 years old)
• English speaker (written and spoken)

You may not qualify if:

• Cardiovascular, neurological diseases, pulmonary abnormalities, kidney disease, liver disease, degenerative neuromuscular disease, history of cancer within past 3 years
• Any history of chronic pain disorder or currently in pain
• Severe psychiatric condition (e.g. schizophrenia, bipolar disorders, mania, autism) and /or psychiatric condition leading to treatment and/or hospitalization within the last 3 years.
• Family (first degree) history of mania, schizophrenia, or other psychoses
• Lifetime alcohol/drug dependence or alcohol/drug abuse in past 3 months
• Pregnancy or breast feeding
• Color-blindness
• Impaired, uncorrected hearing
• History of angioedema
• High blood pressure (above 140 mmHg) or symptomatic low blood pressure
• History of fainting
• Left handed
• Allergies or sensitivities to creams, lotions or food coloring
• Any non-organic implant or any non-removable metal device (e.g. pacemaker, cochlear implants, stents, surgical clips, non-removable piercings)
• Any prior eye injury or the potential of a foreign body in the eye (e.g. worked in metal fields)Persisting functional impairment due to a head trauma

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

Luana Colloca

Baltimore, Maryland, 21201-1512, United States

Location

Related Publications (5)

• Colagiuri B, Schenk LA, Kessler MD, Dorsey SG, Colloca L. The placebo effect: From concepts to genes. Neuroscience. 2015 Oct 29;307:171-90. doi: 10.1016/j.neuroscience.2015.08.017. Epub 2015 Aug 10.

  PMID: 26272535 BACKGROUND

• Colloca L, Benedetti F. Placebo analgesia induced by social observational learning. Pain. 2009 Jul;144(1-2):28-34. doi: 10.1016/j.pain.2009.01.033. Epub 2009 Mar 10.

  PMID: 19278785 BACKGROUND

• Colloca L, Pine DS, Ernst M, Miller FG, Grillon C. Vasopressin Boosts Placebo Analgesic Effects in Women: A Randomized Trial. Biol Psychiatry. 2016 May 15;79(10):794-802. doi: 10.1016/j.biopsych.2015.07.019. Epub 2015 Aug 4.

  PMID: 26321018 BACKGROUND

• Schenk LA, Sprenger C, Geuter S, Buchel C. Expectation requires treatment to boost pain relief: an fMRI study. Pain. 2014 Jan;155(1):150-157. doi: 10.1016/j.pain.2013.09.024. Epub 2013 Sep 26.

  PMID: 24076046 BACKGROUND

• Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL. Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci. 2002 Jun;5(6):514-6. doi: 10.1038/nn849. No abstract available.

  PMID: 11992114 BACKGROUND

MeSH Terms

Conditions

Acute Pain; Diabetes Insipidus; Agnosia; Social Behavior

Interventions

Arginine Vasopressin; Sodium Chloride

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Endocrine System Diseases; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases; Behavior

Intervention Hierarchy (Ancestors)

Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Rachel Massalee
• Organization: University of Maryland School of Nursing

rmassalee@umaryland.edu

4107068244

Study Officials

• Luana Colloca, MD/PHD/MS

  University of Maryland Baltimore School of Nursing

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Randomization will be performed/maintained by the University of Maryland Medical Center Pharmacy. Blind will only be broken in case of a potential medical emergency during the experiment.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: This experiment has a between-subjects design. Participants will be randomized into two groups: AVP and control. Both the experimenter and participant will be blinded to the group allocation. Participants have 50%/50% chance of being placed in either group. Participants in the AVP group will receive intranasal AVP and the participants in the control group will receive intranasal saline before the fMRI experiment. The experiment in the fMRI scanner is divided into two phases: an observational phase in which participants will observe a video of a demonstrator experiencing analgesia and a testing phase in which study participants will receive heat pain to investigate how their pain perception. During both phases there will be a placebo condition (pain with the expectation of having received a treatment) and a control condition (pain without the expectation of having received a treatment). All participants will complete both phases, including the observational and testing phase.

Study Record Dates

• First Submitted: January 16, 2018
• First Posted: February 26, 2018
• Study Start: September 17, 2018
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 20, 2025
• Results First Posted: December 16, 2021

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)