Non-Steroidal Anti-Inflammatory Drug (NSAID) Response and Central Sensitization of Pain in Women With Dysmenorrhea

February 10, 2026 updated by: Laura Payne, Mclean Hospital
Menstrual pain is the most common gynecological complaint and the leading cause of school and work absences in reproductive-age girls and women. One of the primary treatments for menstrual pain is use of nonsteroidal anti-inflammatory drugs (NSAIDs; over-the-counter medications such as naproxen, ibuprofen, or aspirin), although up to 18% of women do not get pain relief from these medications. One reason for this may be due to central sensitization of pain, which is when alterations in the central nervous system change how pain is processed in the brain and experienced. Determining the role of central sensitization in menstrual pain is important because central sensitization is associated with the development of chronic pain. Understanding the relationship between NSAID response and central sensitization is important because it could indicate women who may go on to develop chronic pain later in life. This study would directly address this question. Identifying women at risk for chronic pain would help target new treatments to this vulnerable group to ideally prevent pain from becoming chronic. This is particularly important for women in the military because the severity of menstrual pain is associated with missed work, such that in active-duty military women, less than 4.4% with mild menstrual pain missed work, whereas 20.7% of women with moderate to severe menstrual pain missed work. Addressing the significant impact of menstrual pain for military women will help reducing suffering and potentially decrease the risk of developing future chronic pain problems in this population.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
70

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Massachusetts
      • Belmont, Massachusetts, United States, 02478
        • Mclean Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Female aged 18-50 years
  2. Menstrual pain rated at least 6/10 on a 0 (no pain) to 10 (worst pain possible) NRS for all menstrual cycles in the previous 6 months
  3. Regular menstrual cycles over the past year (at least 9 in the previous 12 months)
  4. Self-reported menstrual cycle averaging 22-35 days
  5. Access to a smartphone and email, and willing/able to receive text messages
  6. Able to read and understand English
  7. Ability and willingness to provide written informed consent.

Exclusion Criteria:

  1. Use of oral contraceptives or any exogenous hormones in the previous 3 months prior to participation
  2. Variable levels of menstrual pain in the previous 6 months
  3. Self-reported symptoms consistent with a chronic pain condition (e.g., pain in any body area lasting longer than 3 months) or previous diagnosis of a chronic pain condition
  4. Currently pregnant or breastfeeding
  5. History of pelvic inflammatory disease or sexually transmitted disease
  6. Acute illness or injury that would potentially impact pain task performance (e.g., fever, flu symptoms) or that affect sensitivity of the extremities (e.g., Reynaud's disease)
  7. Allergy to naproxen or having a health condition that contradicts use of naproxen or affects naproxen metabolism (e.g., kidney disease)
  8. History of high blood pressure or anemia (due to possible complications from NSAID use).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Sodium Naproxen first
Participants take the dose of sodium naproxen during the first menstrual cycle and take the placebo during the second menstrual cycle.
Drug: Sodium Naproxen
One dose of 550mg sodium naproxen taken at the onset of at least moderate pain after menstrual bleeding has started (i.e., at least 6/10 on the 0-10 numeric rating scale).
Drug: Placebo
One dose of placebo capsule taken at the onset of at least moderate pain after menstrual bleeding has started (i.e., at least 6/10 on the 0-10 numeric rating scale).
Experimental: Placebo first
Participants take the dose of placebo during the first menstrual cycle and take the sodium naproxen during the second menstrual cycle.
Drug: Sodium Naproxen
One dose of 550mg sodium naproxen taken at the onset of at least moderate pain after menstrual bleeding has started (i.e., at least 6/10 on the 0-10 numeric rating scale).
Drug: Placebo
One dose of placebo capsule taken at the onset of at least moderate pain after menstrual bleeding has started (i.e., at least 6/10 on the 0-10 numeric rating scale).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall NSAID response
Time Frame: 4 hrs after taking dose during the 2nd medicated menstrual period (i.e., 4 hrs after the first occurrence of pain >= 6 on the 0-10 scale after menstrual bleeding has started during the 2nd medicated menstrual period); # of days varies by participant
NSAID response will be calculated by comparing change in menstrual pain ratings following NSAID to change in menstrual pain ratings following placebo. Calculated by subtracting the placebo cycle response measure from the NSAID cycle response measure. This will result in a single measure indicative of the degree of NSAID response, while controlling for placebo effects
4 hrs after taking dose during the 2nd medicated menstrual period (i.e., 4 hrs after the first occurrence of pain >= 6 on the 0-10 scale after menstrual bleeding has started during the 2nd medicated menstrual period); # of days varies by participant
Urinary naproxen concentration
Time Frame: Four hours after taking the dose (either Naproxen or placebo).
Concentration of naproxen measured in the urine sample.
Four hours after taking the dose (either Naproxen or placebo).
Conditioned pain modulation (CPM)
Time Frame: At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Conditioned pain modulation (CPM) assesses pain inhibition. CPM is calculated as the change in pain50 between when the pressure is applied by itself (test stimulus) and when it is applied while the participant's hand is submerged in cold water (conditioning stimulus).
At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Placebo cycle response
Time Frame: 4 hours after dose is taken.
Change in menstrual pain rating on a 0 (no pain) to 10 (worst pain possible) numeric rating scale before and after the dose is taken. Calculated by subtracting the pre-dose rating from the post-dose rating.
4 hours after dose is taken.
NSAID cycle response
Time Frame: 4 hours after dose is taken.
Change in menstrual pain rating on a 0 (no pain) to 10 (worst pain possible) numeric rating scale before and after the dose is taken. Calculated by subtracting the pre-dose rating from the post-dose rating.
4 hours after dose is taken.
Urinary PGF2α concentration
Time Frame: Four hours after taking the dose (either Naproxen or placebo).
Concentration of prostaglandin F2α (PGF2α) measured in the urine sample.
Four hours after taking the dose (either Naproxen or placebo).
Urinary PGE concentration
Time Frame: Four hours after taking the dose (either Naproxen or placebo).
Concentration of prostaglandin E (PGE) measured in the urine sample.
Four hours after taking the dose (either Naproxen or placebo).
pain50
Time Frame: At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
The amount of pressure in kg/cm2 at the first instance of a pain rating of at least 50/100 during an ascending series of 5-second pressures applied to the dominant thumbnail. [Pressures begin at 0.5 kg/cm2 and increase by steps of 0.5 kg/cm2. The pressure sequence is terminated when the participant reaches their individual tolerance and decides to stop, when the participant reaches the safety maximum amount of pressure, or when the participant rates the pressure >=70 on a 0 (no pain) to 100 (worst pain possible) numeric rating scale.]
At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
pain70
Time Frame: At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
The amount of pressure in kg/cm2 at the first instance of a pain rating of at least 70/100 during an ascending series of 5-second pressures applied to the dominant thumbnail. [Pressures begin at 0.5 kg/cm2 and increase by steps of 0.5 kg/cm2. The pressure sequence is terminated when the participant reaches their individual tolerance and decides to stop, when the participant reaches the safety maximum amount of pressure, or when the participant rates the pressure >=70 on a 0 (no pain) to 100 (worst pain possible) numeric rating scale.]
At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Pressure pain sensitivity (PPS)
Time Frame: At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
The pain rating [on a 0 (no pain) to 100 (worst pain possible) numeric rating scale] of a 5-second, 2.0 kg/cm2 application of pressure to the dominant thumbnail bed.
At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Pressure pain tolerance (PPT)
Time Frame: At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
The last rated pressure delivered in a series of increasing pressure applications to the right thumbnail bed. Each application of pressure lasts for 5 seconds. The pressure sequence is terminated when the participant reaches their individual tolerance and decides to stop, when the participant reaches the safety maximum amount of pressure, or when the participant rates the pressure >=70 on a 0 (no pain) to 100 (worst pain possible) numeric rating scale.
At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Trapezius pressure pain sensitivity (TPPS)
Time Frame: At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
The pain rating [on a 0 (no pain) to 100 (worst pain possible) numeric rating scale] of a 5-second, 4.0 kg/cm2 application of pressure to the dominant trapezius muscle.
At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Time to bladder first sensation
Time Frame: At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
The amount of time in minutes from when the participant began drinking water during the bladder pain task to when she first feels able to urinate.
At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Pain at bladder first sensation
Time Frame: At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
The amount of bladder pain rated on a 0 (no pain) to 100 (worst pain possible) during the bladder pain task when the participant first feels able to urinate.
At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Time to bladder first urge
Time Frame: At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
The amount of time in minutes from when the participant began drinking water during the bladder pain task to when she reaches a point at which she would request to use the restroom if participating in an activity.
At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Pain at bladder first urge
Time Frame: At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
The amount of bladder pain rated on a 0 (no pain) to 100 (worst pain possible) during the bladder pain task when the participant reaches a point at which she would request to use the restroom if participating in an activity.
At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Time to bladder maximum tolerance
Time Frame: At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
The amount of time in minutes from when the participant began drinking water during the bladder pain task to when she is no longer able to hold more urine.
At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
Pain at bladder maximum tolerance
Time Frame: At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)
The amount of bladder pain rated on a 0 (no pain) to 100 (worst pain possible) during the bladder pain task when the participant is no longer able to hold more urine.
At baseline (i.e., during the in-person study visit, during days 8-14 of the menstrual cycle, prior to either of the medication cycles)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mclean Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
United States Department of Defense
Endeavor Health

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Laura Payne, PhD, Mclean Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 25, 2024

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 31, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 8, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 12, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 10, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2023P001489

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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