Behavioral and Neural Phenotypes of Primary Dysmenorrhea in Adolescents

Behavioral and Neural Phenotypes of Primary Dysmenorrhea in Adolescents

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.

Inclusion Criteria:

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

Exclusion Criteria:

1. Use of oral contraceptives or any exogenous hormones in the previous 3 months prior to participation
2. Presence of factors indicative of secondary dysmenorrhea (e.g., self-reported presence of persistent pelvic pain throughout the month)
3. Diagnosis of chronic pain condition (e.g., Irritable bowel syndrome (IBS), functional abdominal pain, interstitial cystitis/painful bladder syndrome)
4. Current self-reported severe depression, bipolar disorder, panic disorder, or ADHD, or current treatment for these conditions
5. Diagnosis of an eating disorder within the last 6 months
6. Current or past diagnosis of any psychotic disorder
7. Currently pregnant
8. Self-reported weekly use of alcohol, cannabis, and/or other illegal substances
9. 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
10. History of pelvic inflammatory disease or sexually transmitted disease
11. 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
12. Developmental delay, diagnosis of autism, or significant cognitive impairment that may preclude understanding of study procedures
13. 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
14. Significant fear of enclosed places (claustrophobia)