Mechanisms and Modulation of Pain Modulatory Capacity

This project proposes to understand the sources of pain variability, and demonstrate that pain variability represents fluctuation in natural pain management. The project further proposes to determine if endogenous capacity to modulate pain can be trained to maximize their body's ability to manage pain, much as the way in which athletic performance can be trained.

Study Overview

• Status: Recruiting
• Conditions: Musculoskeletal Pain
• Intervention / Treatment: Behavioral: Delayed onset muscle soreness.

Detailed Description

Many physiological systems (bioenergy, immune etc.) involve feedback mechanisms to respond to challenges, with increased output or capacity for adaptive change. A similar process is plausible for pain modulation where previous successful pain experience and resolution suggests a pain modulatory system with adaptive capacity. The proposed research examines how a musculoskeletal training program modulates pain response in people with fibromyalgia compared to healthy individuals. Previous research suggests that moderate-high level exercise is associated with attenuation of pain sensitivity and clinical pain intensity in healthy individuals. The proposal seeks to extend findings from previous research and examine how repeated exposure and subsequent adaptations to musculoskeletal pain over time influence pain modulation (PMC). The first outcome is that people with fibromyalgia (FM) will have PMC trainability similar to asymptomatic controls, with the obvious implications for clinical application. The second outcome is that FM patients will demonstrate a deficit in PMC trainability. This outcome will represent an important diagnostic sign, and guide research to additional mechanistic investigation. The third outcome is that impaired or lessened PMC trainability is evident in FM patients and this variability can be explored as an individual difference with clinical implications. The theoretical fourth potential outcome is sensitization in FM patients, however pilot data show that DOMS resolves within the same relative time window as controls. Though not hypothesized, the data and design will allow for examination of this possibility. One potential conclusion from these projects could be that FM arises from an inability to enter a recovery period within which PMC could adapt and increase resilience. The proposal will be able to address at least some of the potential for this inability to recover.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32611
      • Recruiting
      • Unversity of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Asymptomatic people (ie no current pain conditions)
• Participants with widespread muscle pain (WMP) aged 18 years of age and older
• Participants with WMP must meet the ACR (2010) diagnostic criteria of multiple regions of muscle pain
• The asymptomatic group will be free of current wrist/hand, elbow, or shoulder pain and chronic pain conditions (eg irritable bowel syndrome, FM)

Exclusion Criteria:

1. Participation in a conditioning program specific to the biceps in the past 6 months
2. Any report of wrist/hand, elbow, or shoulder pain in the last 3 months
3. Any chronic medical conditions that may affect pain perception (e.g., diabetes, high blood pressure), kidney dysfunction, muscle damage, or major psychiatric disorder
4. Use of any intervention (including but not limited to medication, massage, and stretching) for symptoms induced by pain training for the duration of the study
5. Positive result on pre-MRI metal screening or pregnancy test due to contraindication for the MRI environment.
6. Any participant with ferromagnetic metal in the head, neck, or abdominal cavity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Repeated exposure; Participants will complete four exercise sessions designed to induce delayed onset muscle soreness in the biceps	Behavioral: Delayed onset muscle soreness.; Participants will perform a fatiguing exercise protocol for the upper extremity (biceps muscles)
Active Comparator: Single exposure; Participants will complete one exercise session designed to induce delayed onset muscle soreness	Behavioral: Delayed onset muscle soreness.; Participants will perform a fatiguing exercise protocol for the upper extremity (biceps muscles)
No Intervention: Natural history; Participants will complete all sensory testing and imaging but not perform any exercise sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pain intensity	Pain during movement and pain at rest using the visual analog scale (VAS). Scores are recorded every day by making a handwritten mark on a 10-cm line that represents a continuum between "no pain" and "worst pain.	Baseline up to 10 weeks
Change in thermal quantitative sensory testing	Thermal pain thresholds and suprathreshold responses will be collected using a numeric rating scale anchored 0 "no pain" and 10 "worst pain imaginable". Change will be calculated using simple change scores and more complex multi-level modeling.	Baseline up to 10 weeks
Change in pressure quantitative sensory testing	Pressure pain threshold will be collected using a numeric rating scale anchored 0 "no pain" and 10 "worst pain imaginable". Change will be calculated using simple change scores and more complex multi-level modeling.	Baseline up to 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortical network connectivity	Functional magnetic resonance imaging of regional connectivity among pain-related brain regions	Baseline up to 10 weeks

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2020
• Primary Completion (Anticipated): November 30, 2024
• Study Completion (Anticipated): April 30, 2025

Study Registration Dates

• First Submitted: June 11, 2020
• First Submitted That Met QC Criteria: June 18, 2020
• First Posted (Actual): June 22, 2020

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: May 1, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Musculoskeletal Pain
• Other Study ID Numbers: IRB20190295 3-N; R01AR073745-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No