Oxytocin for Chronic Pain

Overseen By Regina Curry, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must not be taking: Benzodiazepines, Pain medications

Disqualifiers: Neuropathy, Chronic pain, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 1 day per visit, with visits separated by at least 48 hours

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this research is to evaluate the effects of oxytocin (naturally occurring hormone) given by an intramuscular (IM; into the muscle) injection, has on your parasympathetic nervous system. The parasympathetic nervous system is the part of the involuntary nervous system that is sometimes called the "rest and digest" system; the parasympathetic system conserves energy as it slightly slows the heart rate, increases intestinal and gland activity, and relaxes sphincter muscles in the gastrointestinal tract.

Will I have to stop taking my current medications?

The trial requires that participants do not take benzodiazepines or pain medications daily. If you are on these medications, you would need to stop taking them to participate.

Is intranasal oxytocin safe for humans?

Intranasal oxytocin is generally well tolerated in humans, with common side effects including nasal discomfort, tiredness, irritability, diarrhea, and skin irritation. Severe side effects are rare, and studies suggest it is safe for use in conditions like autism spectrum disorder. ^{1 2 3 4 5}

How is the drug oxytocin unique in treating chronic pain?

Oxytocin is unique in treating chronic pain because it is a naturally occurring hormone that may modulate pain by affecting both the central and peripheral nervous systems, offering a non-addictive alternative to traditional pain medications like opioids. It is administered intranasally, which is different from many other pain treatments, and it has shown potential to reduce pain sensitivity without the serious side effects associated with other pain relief drugs. ^{1 6 7 8 9}

What evidence supports the effectiveness of the drug oxytocin for chronic pain?

Research suggests that oxytocin, a naturally occurring hormone, may help reduce pain by affecting how the body processes pain signals. Some studies have shown that oxytocin can enhance the effects of placebos (inactive treatments) and may have potential as a new way to manage chronic pain, but more research is needed to confirm its benefits. ^{1 2 6 8 10}

Who Is on the Research Team?

James C Eisenach, MD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with good health, normal blood pressure or controlled hypertension, and a BMI under 40. It's open to both healthy volunteers and those with knee arthritis. Women of childbearing age must use effective birth control. People can't join if they have certain health risks, are pregnant/nursing/recently pregnant, suffer from chronic pain or diabetes, take daily benzodiazepines/pain meds, or have specific eye conditions.

Inclusion Criteria

My blood pressure and heart rate are within the normal range without medication.

My blood pressure is normal or controlled, and my heart rate is between 45-100 bpm.

I am using effective birth control or abstaining from sex.

Exclusion Criteria

You have had a strong allergic reaction to any ingredient in Pitocin®.

I have neuropathy, chronic pain, diabetes, or take daily pain medication.

I have eye conditions or have had eye surgery that affects my vision or causes tremors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an intramuscular injection of placebo or oxytocin, with pupil diameter measured every 2.5 minutes for 180 minutes

1 day per visit, with visits separated by at least 48 hours

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oxytocin
• Placebo

Trial Overview The study tests the impact of oxytocin (a hormone) given by muscle injection on the 'rest and digest' nervous system activity through pupil response in people with chronic pain/osteoarthritis versus a placebo.

How Is the Trial Designed?

Group I: Placebo, Then Oxytocin Experimental Treatment 2 Interventions

Subjects in this arm will receive Intramuscular placebo injection first then oxytocin injection

Group II: Oxytocin First, then Placebo Experimental Treatment 2 Interventions

Subjects in this arm will receive Intramuscular injection of Oxytocin (Pitocin®) first then placebo injection.

Oxytocin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Pitocin for:

• Induction of labor
• Augmentation of labor
• Control of postpartum bleeding

Approved in European Union as Syntocinon for:

• Induction of labor
• Augmentation of labor
• Control of postpartum bleeding

Approved in Canada as Oxytocin for:

• Induction of labor
• Augmentation of labor
• Control of postpartum bleeding

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

In a study involving 21 women with chronic pelvic pain, intranasal oxytocin showed a significant reduction in pain severity compared to placebo, with about one in three women experiencing a clinically meaningful improvement.

The treatment was well-tolerated, with no significant difference in adverse effects between oxytocin and placebo, suggesting it could be a safe adjuvant option for managing chronic pelvic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal oxytocin as a treatment for chronic pelvic pain: A randomized controlled feasibility study. Flynn, MJ., Campbell, TS., Robert, M., et al.[2021]

This trial aims to evaluate the efficacy of intranasal oxytocin as a non-addictive treatment for chronic pain, involving adults with various pain conditions across three Canadian provinces, using a placebo-controlled, triple-blind design.

Participants will self-administer different doses of oxytocin nasal spray over two weeks, with primary outcomes focused on pain relief and secondary outcomes including emotional function and sleep disturbance, providing a comprehensive assessment of oxytocin's potential analgesic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the efficacy of intranasal oxytocin on pain and function among individuals who experience chronic pain: a protocol for a multisite, placebo-controlled, blinded, sequential, within-subjects crossover trial. Rash, JA., Campbell, TS., Cooper, L., et al.[2022]

Positive verbal suggestions significantly enhanced expectations of pain relief and induced placebo analgesia in 108 female participants, demonstrating that the way treatment is communicated can influence outcomes.

Oxytocin administration did not enhance the placebo effect or expectations for pain or itch relief, suggesting that while verbal suggestions are effective, oxytocin may not play a role in boosting placebo responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing Placebo Effects in Somatic Symptoms Through Oxytocin. Skvortsova, A., Veldhuijzen, DS., Van Middendorp, H., et al.[2019]

Oxytocin, a neuropeptide hormone, shows promise as a potential treatment for chronic pain due to its role in modulating both psychological and physiological processes related to pain.

Current research indicates that oxytocin may effectively alter the pain experience, but more studies are needed to fully understand its mechanisms and therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxytocin and the modulation of pain experience: Implications for chronic pain management. Tracy, LM., Georgiou-Karistianis, N., Gibson, SJ., et al.[2015]

In a study involving 25 male volunteers, the oxytocin analogue carbetocin demonstrated significant anti-nociceptive effects, reducing pain sensitivity in response to electrical stimuli and decreasing the area of capsaicin-induced allodynia.

Carbetocin was shown to effectively increase pain thresholds and reduce pain responses, suggesting its potential as a therapeutic option for managing pain in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers-A randomized, double-blinded, placebo-controlled study. Biurrun Manresa, JA., Schliessbach, J., Vuilleumier, PH., et al.[2021]

A systematic review of five randomized controlled trials involving 223 participants found that long-term use of intranasal oxytocin in treating autism spectrum disorder (ASD) is generally well tolerated, with common side effects like nasal discomfort and tiredness not significantly linked to the treatment.

While some severe adverse events were reported, such as aggression and seizures, the overall safety profile suggests that intranasal oxytocin is safe for use in the ASD population, warranting further research to assess its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis of reported adverse events of long-term intranasal oxytocin treatment for autism spectrum disorder. Cai, Q., Feng, L., Yap, KZ.[2018]

LIT-001, a non-peptide full agonist of the oxytocin receptor, shows promise in reducing inflammatory pain in a rat model, indicating its potential as a new pain treatment option.

Unlike oxytocin, which has a very short half-life and poor absorption, LIT-001 offers a longer-lasting analgesic effect, suggesting it could overcome some of the limitations of traditional oxytocin use in pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Nonpeptide Oxytocin Receptor Agonist for a Durable Relief of Inflammatory Pain. Hilfiger, L., Zhao, Q., Kerspern, D., et al.[2023]

Oxytocin analogues have been developed that are more stable and can effectively penetrate the brain, showing strong potential as non-addictive alternatives for pain relief compared to traditional opioids.

These new oxytocin analogues demonstrate potent pain relief in mice, suggesting they could be a promising option for treating acute and chronic pain while avoiding the negative side effects associated with opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structure-Based Design of Glycosylated Oxytocin Analogues with Improved Selectivity and Antinociceptive Activity. Szabó, LZ., Tanguturi, P., Goodman, HJ., et al.[2023]

This trial will evaluate the efficacy of intranasal oxytocin in improving pain and function in 50 women with chronic pelvic musculoskeletal pain, focusing on its potential to decrease pain sensitivity due to the presence of oxytocin receptors in the uterus.

The study is designed as a double-blind, placebo-controlled crossover trial, which will assess the safety and side effects of oxytocin over a 14-day period, providing valuable insights into its use as an adjuvant treatment for chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol for a placebo-controlled, within-participants crossover trial evaluating the efficacy of intranasal oxytocin to improve pain and function among women with chronic pelvic musculoskeletal pain. Rash, JA., Toivonen, K., Robert, M., et al.[2022]

Chronic pain is a significant issue that not only affects physical health but also mental well-being, often leading to anxiety and depression, and poses an economic burden due to the need for ongoing medical treatment.

Preliminary evidence suggests that oxytocin may be a promising candidate for pain relief, potentially offering a safer and more effective alternative to traditional analgesics like opioids and NSAIDs, which have serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The analgesic effects of oxytocin in the peripheral and central nervous system. Xin, Q., Bai, B., Liu, W.[2022]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Intranasal oxytocin as a treatment for chronic pelvic pain: A randomized controlled feasibility study. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Evaluating the efficacy of intranasal oxytocin on pain and function among individuals who experience chronic pain: a protocol for a multisite, placebo-controlled, blinded, sequential, within-subjects crossover trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Enhancing Placebo Effects in Somatic Symptoms Through Oxytocin. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Oxytocin and the modulation of pain experience: Implications for chronic pain management. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers-A randomized, double-blinded, placebo-controlled study. [2021]

6. Australia pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis of reported adverse events of long-term intranasal oxytocin treatment for autism spectrum disorder. [2018]

7. England pubmed.ncbi.nlm.nih.gov

A Nonpeptide Oxytocin Receptor Agonist for a Durable Relief of Inflammatory Pain. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Structure-Based Design of Glycosylated Oxytocin Analogues with Improved Selectivity and Antinociceptive Activity. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Protocol for a placebo-controlled, within-participants crossover trial evaluating the efficacy of intranasal oxytocin to improve pain and function among women with chronic pelvic musculoskeletal pain. [2022]

10. England pubmed.ncbi.nlm.nih.gov

The analgesic effects of oxytocin in the peripheral and central nervous system. [2022]