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Completed

NCT Number: NCT05900336

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

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.

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Key information

Conditions

Dysmenorrhea Menstrual Pain Menstruation Disturbances Neurologic Manifestations Non-steroidal Anti-inflammatory Drug Pain Pathologic Processes Pathological Conditions, Signs and Symptoms Pelvic Pain Signs and Symptoms

Age range

18 year–50 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

McLean Hospital

Belmont, Massachusetts, 02478, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Female aged 18-50 years
  • 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
  • Regular menstrual cycles over the past year (at least 9 in the previous 12 months)
  • Self-reported menstrual cycle averaging 22-35 days
  • Access to a smartphone and email, and willing/able to receive text messages
  • Able to read and understand English
  • Ability and willingness to provide written informed consent.

Exclusion criteria

  • Use of oral contraceptives or any exogenous hormones in the previous 3 months prior to participation
  • Variable levels of menstrual pain in the previous 6 months
  • 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
  • Currently pregnant or breastfeeding
  • History of pelvic inflammatory disease or sexually transmitted disease
  • 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)
  • Allergy to naproxen or having a health condition that contradicts use of naproxen or affects naproxen metabolism (e.g., kidney disease)
  • History of high blood pressure or anemia (due to possible complications from NSAID use).

Treatment and study plan

Sodium Naproxen

Drug

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).

Placebo

Drug

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).

Primary outcomes

  1. 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

  2. Urinary naproxen concentration

    Time frame: Four hours after taking the dose (either Naproxen or placebo).

    Concentration of naproxen measured in the urine sample.

  3. 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).

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.]

  6. 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.]

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

Sponsors and collaborators

Lead sponsor

Mclean Hospital

Other

Collaborators

  • Endeavor Health
  • United States Department of Defense

Registry information

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Jun 12, 2023
Registry last updated
Feb 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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