Behavioral and Neural Phenotypes of Primary Dysmenorrhea in Adolescents

NCT04685343 | Completed

• 1 other identifier: 2019P001729
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 1

Brief Summary

The study will use primary dysmenorrhea (PD; menstrual pain without an identified organic cause) as a model to examine biomarkers associated with menstrual and non-menstrual bodily pain in adolescent girls, ages 13-19. Participants will undergo extensive phenotyping including pain inhibition testing and multimodal neuroimaging to obtain indices brain structure and function at baseline and 12 months later. Menstrual pain severity and non-menstrual bodily pain will be assessed monthly for 24 months. Aims of the study are: 1) to identify the central mechanisms of PD using measures of pain inhibition and brain structure and connectivity of sensorimotor, default, emotional arousal, and salience networks, 2) to determine deficits in pain inhibition and alterations in brain structure and network connectivity that predict the one-year developmental trajectories of menstrual pain and non-menstrual bodily pain, and 3) to identify the dynamic relationship between alterations in pain inhibition and brain structure and connectivity with symptom change in menstrual pain and non-menstrual bodily pain. We hypothesize that deficits in endogenous pain inhibition and alterations in brain structure, connectivity, and function of regional networks will be positively associated with menstrual pain severity ratings at baseline and predict the trajectory of menstrual and non-menstrual bodily pain over 2 years. The results are expected to identify specific mechanisms and characteristics that predict the transition from acute/cyclical pain to persistent or chronic pain, which will support the development of therapies to prevent the transition from recurrent to chronic pain in adulthood.

Conditions

Primary Dysmenorrhea

Outcome Measures

Primary Outcomes (10)

• Menstrual pain

  Rating of average pain during the first two days of the most recent menstrual period on a 0 (no pain) to 10 (worst pain possible) numeric rating scale.

  Baseline

• Change in menstrual pain from baseline to 12-months post baseline

  Change in the rating of average pain during the first two days of the most recent menstrual period on a 0 (no pain) to 10 (worst pain possible) numeric rating scale.

  At baseline and 12 months after baseline

• Change in bodily pain from baseline to 12-months post baseline

  Change in the number of bodily locations endorsed as painful during the prior month.

  At baseline and 12 months after baseline

• Pressure pain sensitivity (PPS)

  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 right thumbnail bed.

  At baseline

• Pressure pain tolerance (PPT)

  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 \>=80 on a 0 (no pain) to 100 (worst pain possible) numeric rating scale.

  At baseline

• Trapezius pressure pain threshold (TPPTh)

  The amount of pressure, applied by a pressure algometer to the participant's trapezius muscle, needed for the pressure stimulus to first feel painful to the participant.

  At baseline

• Conditioned pain modulation (CPM)

  Conditioned pain modulation (CPM) assesses pain inhibition. CPM is calculated as the change in the TPPTh 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

• Gray matter volume

  Gray matter regional volume and surface area will be measured from images obtained during the fMRI session.

  At baseline

• White matter fiber tract values

  Obtained from fiber tracking using images obtained during diffusion tensor imaging (DTI). Values represent anatomical connectivity of cortical and subcortical brain regions.

  At baseline

• Resting state networks

  Calculated from images obtained during resting state fMRI. Region-to-region connectivity indices are obtained by correlating fMRI time series corrected for physiological noise and motion. Region-to-region connectivity strength of the regions of interest (i.e., salience, sensorimotor, emotional arousal, and default mode networks) will be assessed for each participant.

  At baseline

Secondary Outcomes (10)

• Change in menstrual pain from 12-months post baseline to 24-months post baseline

  12 months after baseline and 24 months after baseline

• Change in bodily pain from 12-months post baseline to 24-months post baseline

  12 months after baseline and 24 months after baseline

• Salivary pro-inflammatory cytokines

  Three time points during each of two study visits: during questionnaire completion (approx. 20 min. after arrival), immediately after the imaging session (approx. 90 min. after arrival), and following the final pain task (approx. 120 min after arrival)

• Trapezius pressure pain threshold (TPPTh)

  12 months after baseline

• Change in conditioned pain modulation (CPM) from baseline to 12-months post baseline

  At baseline and 12 months after baseline

Study Arms (1)

fMRI and laboratory pain induction

EXPERIMENTAL

Behavioral: Quantitative Sensory Testing; Other: fMRI

Interventions

Quantitative Sensory Testing BEHAVIORAL

Quantitative sensory testing (QST) consisting of 4 pain induction and sensory sensitivity tasks (i.e., pressure applied to the thumbnail, arms, shoulders, and lower abdomen, a cold water task, and one video-watching task).

fMRI and laboratory pain induction

fMRI OTHER

Functional magnetic resonance imaging (fMRI) session consisting of structural and functional brain scans.

fMRI and laboratory pain induction

Eligibility Criteria

• Age: 13 Years - 19 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Female aged 13-19 years
• Self-reported menstrual cycle averaging 22-35 days
• Regular menstrual cycles for at least 6 months
• Access to a smartphone or email
• Right handed
• Body Mass Index (BMI) of 35 or less
• Able to read and understand English
• Ability and willingness to provide written informed assent/consent
• Availability of a parent to provide written parental permission (for participants under age 18)

You may not qualify if:

• Use of oral contraceptives or any exogenous hormones in the previous 3 months prior to participation
• Presence of factors indicative of secondary dysmenorrhea (e.g., self-reported presence of persistent pelvic pain throughout the month)
• Diagnosis of chronic pain condition (e.g., Irritable bowel syndrome (IBS), functional abdominal pain, interstitial cystitis/painful bladder syndrome)
• Current self-reported severe depression, bipolar disorder, panic disorder, or ADHD, or current treatment for these conditions
• Diagnosis of an eating disorder within the last 6 months
• Current or past diagnosis of any psychotic disorder
• Currently pregnant
• Self-reported weekly use of alcohol, cannabis, and/or other illegal substances
• Use of stimulants (including methamphetamine and/or medications for the treatment of ADHD) or opioids in the previous 3 months. Participants who use other analgesics will be included but will be requested to not take these analgesics within the previous 24 hours of the laboratory session
• 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). Potential participants who are being treated for cardiovascular disease(s) will be included pending discussion with the participant's primary physician
• Developmental delay, diagnosis of autism, or significant cognitive impairment that may preclude understanding of study procedures
• Presence of certain ferromagnetic appliance or implants (braces, retainers, spacers, wires, screws, etc.) in the mouth or any other body part that may be a contraindication for the magnetic resonance imaging (MRI) scanner
• Significant fear of enclosed places (claustrophobia)

Sponsors & Collaborators

• Mclean Hospital: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

Related Publications (1)

• Payne LA, Handy AB, Seidman LC, Mitchell CM, Edwards RR. Multisensory sensitivity predicts menstrual pain and widespread pain trajectories over 12 months in adolescents with and without primary dysmenorrhea. Pain. 2026 Apr 1;167(4):943-951. doi: 10.1097/j.pain.0000000000003868. Epub 2025 Nov 24.

  PMID: 41284472 DERIVED

Study Officials

• Laura Payne, PhD

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 28, 2020
• Study Start: December 14, 2020
• Primary Completion: December 24, 2025
• Study Completion: December 24, 2025
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

US (1)