Relationships of Affect and Neuroinflammation With Clinical Pain in Veterans With Fibromyalgia
NCT Number: NCT06574165
Acronym: RAN
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Fibromyalgia
Interventions: BEHAVIORAL: Moderate Intensity Continuous Training
Sponsor: VA Office of Research and Development
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: SUPPORTIVE_CARE
Start Date: 2024-11-01
Completion Date: 2026-10-30
Locations: Birmingham VA Medical Center, Birmingham, AL, Birmingham, Alabama, 35233-1927, United States

Summary:
Fibromyalgia (FM) is a chronic pain condition that disproportionately impacts Veterans. Individuals diagnosed with FM patients experience lower self-esteem and positive affect, as well as greater levels of depression, anxiety, negative affect, and pain catastrophizing. Among those experiencing FM, clinical and experimental pain are associated with specific dispositional trait profiles, which are indexed by levels of negative affect and positive affect. Neuroinflammation and inflammation also play a role in FM- related affect and pain. Recent studies that have highlighted neuroinflammation and inflammation as physiological mechanisms associated with changes in dysregulated affect and chronic pain. Veterans with FM can ameliorate their dispositional traits-i.e., increasing positive affect and reducing negative affect-by participating in exercise. However, a gap exists regarding how to optimally engage Veterans with FM in an exercise program. Thus, to fully take advantage of all potential therapeutic benefits of exercise for FM, there is a critical need to identify those factors underlying exercise engagement for FM pain management. The purpose for this study is to 1) determine associations of dispositional trait styles, neuroinflammation, and inflammation with pain outcomes in Veterans with FM; and 2) develop and design a Veteran-informed exercise program.

Primary Outcome Measures: Dispositional Trait Styles, As a measurement of affect, participants will complete the Positive and Negative Affect Schedule and indicate the frequency with which they generally experience 10 positive (i.e., interested, excited) and 10 negative (i.e., distressed, upset) feelings. Items are rated ranging from 1 (very slightly or not at all) to 5 (extremely) with a total subscale ranging from 10 to 50., Baseline to 12 weeks|Feasibility, Feasibility will be percentage of exercise sessions attended., Baseline to 12 weeks|Clinical Pain Severity, Participants will self-report a number between 0-100 describing the intensity of their pain, such that 0= no pain and 100 = the most intense pain imaginable. Any integer from 0 to 100 can be provided., Baseline to 12 weeks|Pain Threshold, Pain threshold refers to the intensity at which a stimulus is first perceived as painful. Pressure stimuli will be delivered to their forearm and lower back using a handheld pressure algometer. The pressure will gradually increase until the participant responds by pressing a button on a handheld device. For pressure threshold, participants will be instructed to press the button when the sensation "first becomes painful.", Baseline to 12 weeks|Temporal Summation of Pain, Temporal summation refers to a form of endogenous pain facilitation characterized by the perception of increased pain despite constant or even reduced peripheral afferent input. Temporal summation is presumed to be the psychosocial manifestation of wind-up. Wind-up is a phenomenon where repetitive stimulation of C primary afferents at rates greater that 0.3 Hertz produces a slowly increasing response of second-order neurons in the spinal cord. Temporal summation will be assessed using a nylon monofilament calibrated to bend a 300g of pressure on the back of the hand and lower back. Participants will be instructed to provide a verbal 0-100 rating of pain following a single contact of the monofilament. Then, participants will be instructed to provide another 0-100 rating of pain following a series of 10 contacts of the monofilament. This procedure will repeated twice at each location and pain ratings will be averaged across the two trials., Baseline to 12 weeks|Conditioned Pain Modulation, A routinely used quantitative sensory testing protocol for the measurement of endogenous pain inhibition is conditioned pain modulation, which refers to the reduction in pain from one stimulus (the test stimulus) produced by the application of a second pain stimulus at a remote body site (the conditioning stimulus). Conditioned pain modulation is believed to reflect the perceptual manifestation of diffuse noxious inhibitory controls, whereby ascending projections from one noxious stimulus activate supraspinal structures that trigger descending inhibitory projections to the dorsal horn. Participants will undergo four cold pressor immersions that consists of placing their non-dominant hand, up to the wrist, into circulating cold water for up to 1 minute and will provide a 0-100 rating of pain. Following each immersion, a handheld force algometer will be applied to either their forearm or lower back and press a handheld button to indicate when the pressure first becomes painful., Baseline to 12 weeks|C-reactive protein, A marker of pro-inflammation from blood draws, Baseline to 12 weeks|Tumor necrosis factor- alpha, A marker of pro-inflammation from blood draws, Baseline to 12 weeks|Interleukin-6, A marker of pro-inflammation from blood draws, Baseline to 12 weeks|Interleukin- 10, A marker of pro-inflammation from blood draws, Baseline to 12 weeks|Interleukin- 8, A marker of pro-inflammation from blood draws, Baseline to 12 weeks|Myo-inositol, marker of neuroinflammation measured via magnetic resonance spectroscopy imaging., Baseline to 12 weeks|N-acetylaspartate, marker of neuroinflammation measured via magnetic resonance spectroscopy imaging., Baseline to 12 weeks|Choline, marker of neuroinflammation measured via magnetic resonance spectroscopy imaging., Baseline to 12 weeks|Lactate, marker of neuroinflammation measured via magnetic resonance spectroscopy imaging., Baseline to 12 weeks|Creatine, marker of neuroinflammation measured via magnetic resonance spectroscopy imaging., Baseline to 12 weeks|Brain Temperature, marker of neuroinflammation using absolute brain temperatures (in °C) from magnetic resonance spectroscopy imaging., Baseline to 12 weeks|Exercise Benefits and Barriers, Participants will be asked to complete the Exercise Barriers and Benefits Scale that assesses perceived benefits and barriers to exercise to rank agreement with 29 statements, where 4='strongly agree' and 1='strongly disagree.', Baseline to 12 weeks|Exercise Perceptions, Semi-structured interviews will be conducted around topics related to current exercise behavior and any barriers they have to current exercise behavior, and will elicit participants' views on what an ideal exercise program would be., Baseline to 12 weeks