Vasopressin for Acute Pain

Overseen By Rachel Massalee, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Maryland, Baltimore

Must not be taking: Opiates, Cocaine, Methamphetamines, others

Disqualifiers: Cardiovascular, Neurological, Psychiatric, others

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how vasopressin, a chemical affecting social interaction, influences pain perception through observational learning. Participants will receive either vasopressin or a placebo via a nasal spray and then watch a video of someone experiencing pain relief. Researchers will use brain scans to observe vasopressin's effect on the brain's response to this learning. The trial seeks right-handed individuals without chronic pain or severe psychiatric conditions who can undergo MRI scans. As a Phase 1 and Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group. Participants have the opportunity to contribute to groundbreaking pain management research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a history of drug dependence or abuse in the past 3 months, you may not be eligible to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that arginine vasopressin, the treatment tested in this trial, may help relieve pain. One study found that vasopressin can raise the pain threshold, potentially reducing pain from typically painful stimuli. Another study discovered that nasal administration of vasopressin significantly reduced pain in people recovering from surgery, suggesting it could be a promising option for pain relief.

Regarding safety, these studies indicate that vasopressin is generally well-tolerated in humans, with no serious side effects reported. It's important to note that this trial is in the early stages, focusing primarily on safety. The treatment is being closely monitored to ensure it is safe for participants. Consulting a healthcare professional is advisable to understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard pain relief options like NSAIDs or opioids, which have varying mechanisms and side effects, arginine vasopressin is unique because it targets pain through a novel pathway. This treatment uses the hormone vasopressin, which is known for its role in water retention and blood pressure regulation, but here it's being explored for its potential to modulate pain perception. Researchers are excited because this intranasal delivery method could offer rapid pain relief with potentially fewer side effects compared to systemic medications. This approach not only opens up a new avenue for managing acute pain but also highlights the versatility of vasopressin beyond its traditional roles.

What evidence suggests that vasopressin might be an effective treatment for acute pain?

In this trial, participants will receive either arginine vasopressin (AVP) or a placebo to evaluate its effectiveness in reducing acute pain. Research has shown that AVP can reduce pain when administered through a nasal spray. Studies have found that it can lessen pain from headaches and other types of pain, such as those caused by pressure or heat. AVP interacts with the brain's natural pain-relief systems, making pain feel less intense. These findings suggest that AVP could be a promising option for managing sudden pain by helping to control pain perception. ^{1 2 3 6 7}

Who Is on the Research Team?

Luana Colloca, MD/PHD/MS

Principal Investigator

University of Maryland Baltimore School of Nursing

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 18-55 who experience acute pain. It's designed to understand how a neurotransmitter involved in social interactions, vasopressin, affects learning about pain relief from watching others and how this influences personal pain perception.

Inclusion Criteria

I can speak and write in English.

Exclusion Criteria

Failed drug test (testing for opiates, cocaine, methamphetamines, amphetamines, and THC)

I have a long-term pain condition or am currently experiencing pain.

A close family member has had mania, schizophrenia, or psychosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observational Learning

Participants observe a video of a demonstrator experiencing analgesia to learn about pain relief through social observation

1 day

1 visit (in-person)

Testing

Participants receive heat pain to investigate how pain perception was influenced by observational learning

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the testing phase

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Arginine Vasopressin

Trial Overview Participants will receive either vasopressin or saline via nasal spray. They'll then watch videos showing others experiencing pain relief during an fMRI scan to see if observing these scenarios can influence their own sensation of pain through learned expectations.

How Is the Trial Designed?

Group I: Arginine vasopressin Experimental Treatment 3 Interventions

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.).

Group II: Saline Placebo Group 3 Interventions

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.

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

Microinjection of arginine vasopressin (AVP) into the caudate nucleus of rats increased their pain threshold in a dose-dependent manner, indicating its role in reducing pain sensitivity.

The use of an AVP-receptor antagonist reversed the pain-relieving effects of AVP, suggesting that AVP in the caudate nucleus is crucial for its antinociceptive effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arginine vasopressin in the caudate nucleus plays an antinociceptive role in the rat. Yang, J., Chen, JM., Liu, WY., et al.[2022]

Intranasal administration of arginine vasopressin (AVP) significantly reduced orthopedic pain in patients 2-4 weeks post-surgery, demonstrating a dose-dependent effect based on visual analogue scale (VAS) measurements.

The study, which included 653 orthopedic patients, found that AVP levels in cerebrospinal fluid (CSF) increased after treatment, correlating negatively with pain levels, while not affecting plasma AVP concentrations or vital signs, indicating a safe profile for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal Vasopressin Relieves Orthopedic Pain After Surgery. Yang, FJ., Ma, L., Yang, J., et al.[2020]

In a study involving 157 ICU patients and 70 healthy volunteers, both copeptin and arginine vasopressin (AVP) levels were significantly higher in critically ill patients, indicating their potential role in assessing the severity of illness.

The copeptin/AVP ratio was notably elevated in patients with sepsis and systemic inflammatory response syndrome (SIRS), suggesting that copeptin may not accurately reflect AVP levels in these conditions, which could impact treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Copeptin and arginine vasopressin concentrations in critically ill patients. Jochberger, S., Morgenthaler, NG., Mayr, VD., et al.[2006]

The AVP analogue [dPTyr (Me)]AVP effectively blocks the blood pressure-raising effects of exogenous arginine vasopressin (AVP) in conscious rats, demonstrating its potential as a vasopressor antagonist.

In fluid-deprived rats with elevated endogenous AVP levels, administration of the AVP analogue resulted in a significant drop in blood pressure, primarily due to reduced peripheral vascular resistance, indicating its efficacy in modulating vascular responses under certain physiological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular effects of arginine vasopressin during fluid deprivation in the rat. Aisenbrey, GA., Handelman, WA., Arnold, P., et al.[2019]

In an in vitro study using cerebellar brain slices from adult rats, vasopressin did not affect the survival rate of Purkinje cells after simulated ischemia-reperfusion, indicating no direct protective or harmful effect on brain injury.

The study tested various concentrations of vasopressin (ranging from 5 to 500 pg/ml) and found no significant differences in cell survival compared to the control group, suggesting that vasopressin may not play a role in mitigating brain injury in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of vasopressin on survival of Purkinje neurons in rat cerebellar slices after an in vitro simulated ischemia. Jeon, YS., Lee, SY., Lee, J., et al.[2019]

Administering arginine vasopressin (AVP) directly into the brains of rats led to a rapid decrease in body temperature, indicating a significant physiological effect.

Repeated administration of AVP resulted in increased sensitivity, with the same dose causing convulsions on the second injection and even lower doses (10 ng) triggering seizures, highlighting potential safety concerns with its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Convulsive and hypothermic effects of vasopressin in the brain of the rat. Kasting, NW., Veale, WL., Cooper, KE.[2019]

Intraventricular injections of arginine vasopressin (AVP) significantly increased pain thresholds in rats, indicating its potential role in enhancing antinociception, particularly at doses of 50 or 100 ng.

The study found that AVP's effects on pain modulation are localized to specific brain regions, as pain stimulation altered AVP levels in the hypothalamus but did not affect levels in the pituitary, spinal cord, or serum.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Only through the brain nuclei, arginine vasopressin regulates antinociception in the rat. Yang, J., Song, CY., Liu, WY., et al.[2006]

Arginine vasopressin (AVP) is effective in treating refractory shock conditions, such as severe sepsis and cardiogenic shock, by restoring vasomotor tone and preserving renal blood flow, especially in patients with low plasma levels of AVP.

Low doses of AVP and its analog terlipressin can be beneficial as adjunct vasopressors in advanced shock states that do not respond to traditional treatments, making them a valuable option in critical care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of vasopressin in current anesthetic practice. Park, KS., Yoo, KY.[2019]

In a study involving 16 healthy dogs, arginine vasopressin (AVP) at doses of 0.1 and 1.0 U/kg/min significantly increased mean arterial pressure and systemic vascular resistance, but also led to decreased heart rate and cardiac output, indicating potential cardiovascular risks at higher doses.

The findings suggest that while AVP can effectively raise blood pressure, its use should be carefully monitored in clinical settings, especially at doses above 0.01 U/kg/min, due to the associated negative effects on heart function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vasopressin intravenous infusion causes dose dependent adverse cardiovascular effects in anesthetized dogs]. Martins, LC., Sabha, M., Paganelli, MO., et al.[2019]

In a study of 66 cardiac surgical patients, the use of arginine vasopressin (AVP) in addition to norepinephrine did not increase the predicted mortality rates, suggesting it is a safe option for treating vasodilatory shock.

However, patients receiving AVP experienced significantly higher rates of renal complications (36.4% vs. 9.1%) and infections (30.3% vs. 3.0%), indicating potential safety concerns despite its efficacy in managing shock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vasopressin, when added to norepinephrine, was not associated with increased predicted mortality after cardiac surgery. Suojaranta-Ylinen, RT., Vento, AE., Pätilä, T., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4371647/

A Review of the Nonpressor and Nonantidiuretic Actions of the ... Arginine vasopressin has a significant effect on pain perception ... demonstrated that, in acute headaches, intranasal AVP was effective in reducing pain.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24089014/

Role of central arginine vasopressin receptors in the ... Recent studies have demonstrated that arginine vasopressin (AVP) plays a crucial role in pain modulation. In addition, our previous studies have ...

3. journals.physiology.org journals.physiology.org/doi/prev/20241023-aop/abs/10.1152/ajpendo.00361.2024

Arginine vasopressin induces analgesic effects and inhibits ... In the present study, we observed that intranasal delivery of AVP inhibited mechanical pain, thermal pain, and spontaneous pain sensitivity in ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1526590023001475

The Bidirectional Impact Of Arginine-Vasopressin Receptor ... We will present data on the efficacy of targeting Avpr1a overexpression using specific-antisense oligonucleotide (ASO) and on the role of the microbiome in risk ...

5. withpower.com withpower.com/trial/phase-2-diabetes-insipidus-8-2018-df7fe

Vasopressin for Acute Pain · Info for Participants In a study involving 157 ICU patients and 70 healthy volunteers, both copeptin and arginine vasopressin (AVP) levels were significantly higher in critically ill ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2352345X17300164

Association of Variants of Arginine Vasopressin and ... Demographic, clinical, laboratory, radiologic, and outcomes data were recorded prospectively. For the purpose of the present study, we selected only ...

7. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-025-05540-2

Vasopressin and its analogues in patients with septic shock The VANCS II trial found that vasopressin administration had no renal protective effect and did not reduce the need for renal replacement ...