Test Retest Reliability of OA and OH

Study Overview
=================
Brief Summary
-----------------
The goal of this study is to measure the test retest reliability of offset analgesia (OA) and onset hyperalgesia (OH) across multiple study visits. OA and OH are quantitative sensory tests (QST) thought to measure how the brain modulates pain. This study will use a heat thermode to induce OA and OH in healthy, pain-free volunteers across 3 study visits. Additional QST measures and survey data relevant to pain modulation will be collected. This study lays the foundation required to use OA and OH as tools to measure pain modulation in clinical trials. Following their validation, we anticipate that OA and OH will serve as predictive and therapeutic biomarkers, which will aid both in the development of novel analgesics and in treatment selection leading to the personalization of pain management.

Official Title
-----------------
Test Retest Reliability of Offset Analgesia and Onset Hyperalgesia Paradigm

Conditions
-----------------
Analgesia, Pain Catastrophizing, Pain

Intervention / Treatment
-----------------
* Behavioral: Medoc cutaneous probe
* Behavioral: Quantitative sensory testing
* Behavioral: Computer tasks


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy volunteers with no chronic pain issues who can understand the study procedures Exclusion Criteria: History of chronic pain Current significant pain disorder Active ongoing pain every day that is acute or chronic in duration Recent history of migraine (1 attack in last 24 months) Lifetime history mood disorders (anxiety, depression, bipolar) or psychotic disorders. Subjects taking psychotropics (e.g. benzodiazepines, antidepressants), or medications known to affect the autonomic nervous system (e.g. beta-receptor agonists or antagonists) will be excluded. Cognitive impairment affecting the ability to provide informed consent, understand directions, and participate in study procedures Uncontrolled or unstable medical disorder preventing participation in study procedures Pregnancy Tattoos on forearm History of brain surgery Nonambulatory status Heart problems such as an irregular heart beat or coronary artery disease Neurological problems such as seizure, fainting spells, recurrent severe headache, stroke, transient ischemic attack High blood pressure Severe liver disease Severe gastrointestinal disease Chronic severe infectious disease (e.g. HIV/AIDS)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Volunteers<br>QST devices and computer tasks are used to measure OA, OH, pain intensity, and other outcomes | Behavioral: Medoc cutaneous probe<br>* A computer-controlled probe delivers temperatures to the skin to measure pain, OA, and OH<br>Behavioral: Quantitative sensory testing<br>* Standard methods involving pinprick, pressure, heat, and cold applied to the skin are used to measure sensation and pain<br>Behavioral: Computer tasks<br>* QST and computer tasks are used to measure changes in pain intensity<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Offset analgesia and onset hyperalgesia | Pain intensity difference during heat stimuli measured on a 0-100 sliding scale (0 is no pain, 100 is the most intense pain imaginable) at baseline | baseline | 
| Test retest reliability of offset analgesia and onset hyperalgesia | Pain intensity difference during heat stimuli measured on a 0-100 sliding scale (0 is no pain, 100 is the most intense pain imaginable) at 1 week after baseline | 1 week post baseline | 
| Test retest reliability of offset analgesia and onset hyperalgesia | Pain intensity difference during heat stimuli measured on a 0-100 sliding scale (0 is no pain, 100 is the most intense pain imaginable) at 4 weeks after baseline | 4 weeks post baseline | 
| Differences in brain region activation- QST (quantitative sensory tests) | Difference in brain region activation (as measured by oxygenated hemoglobin, HbO) between central nervous system inhibition and control stimuli during QST procedures. | baseline | 
| Test retest reliability in brain region activation- QST (quantitative sensory tests) | Difference in brain region activation (as measured by oxygenated hemoglobin, HbO) between central nervous system inhibition and control stimuli during QST procedures at 1 week after baseline | 1 week post baseline | 
| Test retest reliability in brain region activation- QST (quantitative sensory tests) | Difference in brain region activation (as measured by oxygenated hemoglobin, HbO) between central nervous system inhibition and control stimuli during QST procedures at 4 weeks after baseline | 4 weeks post baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in resting fNIRS signaling | Differences in fNIRS resting state connectivity as measured by brain region activation | baseline | 
| Questionnaire score- State Trait Anxiety Inventory (STAI) Y1-2 | Standardized survey score of state trait anxiety inventory Y1 and Y2 assessing anxiety before QST procedures on visit 1 only. State Anxiety Score ranges from 20-80. Trait Anxiety Score ranges from 20-80. Higher scores indicate worse anxiety state and trait symptoms. | baseline | 
| Questionnaire score- Pain Catastrophizing Scale (PCS) | Standardized survey score assessing pain perception before QST procedures at visit 1 only. Rumination subscale score ranges from 0-16. Magnification subscale score ranges 0-12. Helplessness subscale score ranges from 0-24. Total score can be calculated by summing subscales. Total score ranges from 0-52, with higher scores indicating more pain catastrophizing. | baseline | 
| Questionnaire score- STAI Y1 post testing | Standardized survey score of state trait anxiety inventory Y1 assessing anxiety immediately after QST procedures measured at all 3 visits. Higher scores indicate worse anxiety state. | baseline | 
| Questionnaire score- STAI Y1 post testing | Standardized survey score of state trait anxiety inventory Y1 assessing anxiety immediately after QST procedures measured at all 3 visits. Higher scores indicate worse anxiety state. | 1 week after baseline | 
| Questionnaire score- STAI Y1 post testing | Standardized survey score of state trait anxiety inventory Y1 assessing anxiety immediately after QST procedures measured at all 3 visits. Higher scores indicate worse anxiety state. | 4 weeks after baseline | 
| Questionnaire score- Situational Pain Catastrophizing Scale post testing | Standardized survey score assessing pain perception immediately after QST procedures are completed at each visit. Scores range from 0-24, with higher scores representing more pain catastrophizing. | baseline | 
| Questionnaire score- Situational Pain Catastrophizing Scale post testing | Standardized survey score assessing pain perception immediately after QST procedures are completed at each visit. Scores range from 0-24, with higher scores representing more pain catastrophizing. | 1 week after baseline | 
| Questionnaire score- Situational Pain Catastrophizing Scale post testing | Standardized survey score assessing pain perception immediately after QST procedures are completed at each visit. Scores range from 0-24, with higher scores representing more pain catastrophizing. | 4 weeks after baseline | 
| Questionnaire score- Beck Depression Inventory-II (BDI-II) | Standardized survey assessing depression at the start of visit 1. Scores range from 0-63. Total score of 0-13 is considered minimal range of depression, 14-19 is mild, 20-28 is moderate, and 29-63 is severe depression. | baseline | 
| Questionnaire score- Generalized Anxiety Disorder 2-item (GAD-2) | Standardized survey score of GAD-2 assessing anxiety at the start of visit 1. Scores range from 0-6. Higher scores indicate higher likelihood of having GAD. | baseline | 
| Questionnaire score- Multidimensional Assessment of Interoceptive Awareness (MAIA) Version 2 | Standardized survey score of MAIA-2 assessing mindfulness at the start of visit 1. Total scores range from 0-160 with 8 subscales. Higher scores indicate higher levels of mindfulness. | baseline | 
| Questionnaire score- Multidimensional Assessment of Interoceptive Awareness (MAIA) Version 2 post testing | Standardized survey score of MAIA-2 assessing mindfulness after QST measured at all 3 visits. Total scores range from 0-160 with 8 subscales. Higher scores indicate higher levels of mindfulness. | baseline | 
| Questionnaire score- Multidimensional Assessment of Interoceptive Awareness (MAIA) Version 2 post testing | Standardized survey score of MAIA-2 assessing mindfulness after QST measured at all 3 visits. Total scores range from 0-160 with 8 subscales. Higher scores indicate higher levels of mindfulness. | 1 week after baseline | 
| Questionnaire score- Multidimensional Assessment of Interoceptive Awareness (MAIA) Version 2 post testing | Standardized survey score of MAIA-2 assessing mindfulness after QST measured at all 3 visits. Total scores range from 0-160 with 8 subscales. Higher scores indicate higher levels of mindfulness. | 4 weeks after baseline | 
| Pain intensity | Changes in pain intensity during quantitative sensory tests and computer tasks measured on a 0-100 sliding scale (0 is no pain, 100 is the most intense pain imaginable) | baseline | 
| Pain intensity | Changes in pain intensity during quantitative sensory tests and computer tasks measured on a 0-100 sliding scale (0 is no pain, 100 is the most intense pain imaginable) | 1 week after baseline | 
| Pain intensity | Changes in pain intensity during quantitative sensory tests and computer tasks measured on a 0-100 sliding scale (0 is no pain, 100 is the most intense pain imaginable) | 4 weeks after baseline |