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NEPAL (Neuromodulatory Examination of Pain and Mobility Across the Lifespan)

Neuroimaging Age-related Versus Pain-related Changes in Pain Modulation

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT02488863
Acronym
NEPAL
Enrollment
105
Registered
2015-07-02
Start date
2015-07-31
Completion date
2024-02-04
Last updated
2025-03-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Musculoskeletal Pain, Pain, Chronic

Keywords

Older adults, Chronic Pain, Musculoskeletal

Brief summary

Musculoskeletal pain represents the leading cause of disability worldwide. It has been traditionally attributed to peripheral mechanisms, but peripheral damage, inflammation, and psychological factors have failed to significantly account for the presence, absence, or severity of chronic musculoskeletal pain (CMP). Recent studies show that individuals with CMP exhibit dysfunctional pain modulation supporting a significant central nervous system (CNS) contribution. However, the CNS mechanisms underlying these changes in pain modulation are not currently known, nor is their relation to clinical pain progression. The proposed pilot examines brain circuits recently described in predicting the transition from acute to chronic pain, in predicting clinical and experimental pain changes as well as physical performance and mobility changes in older persons with musculoskeletal pain over a one year period. The findings will provide novel and important information regarding the mechanisms underlying aberrant pain processing and its functional consequences in older adults with musculoskeletal pain. The information learned can be subsequently used to target treatment and prevention strategies in future studies of older adults. The central hypothesis is that increased functional and structural connectivity of cortico-striatal regions will be significantly associated with baseline clinical and experimental pain and decreased physical function in persons with CMP and will account for more rapid clinical pain and disability progression over time.

Detailed description

Chronic musculoskeletal pain (CMP) is the most common, non-malignant disabling condition that affects at least one in four older people. The most common painful musculoskeletal conditions among older adults are osteoarthritis, low back pain, fibromyalgia, chronic shoulder pain, knee pain, myofascial pain syndrome and previous fracture sites. Recent studies demonstrate generalized alterations of pain processing among older individuals with CMP. An improved understanding of the mechanisms underlying CMP-related changes in pain modulation will provide a basis for the development of targeted preventive and rehabilitative strategies. In light of evidence emphasizing plasticity of white matter connections, and the potential pain relieving effects of non-invasive brain stimulation interventions, it seems reasonable to identify these connections as potential targets for future treatment approaches. Given the expected growth of the older population, such strategies could have a monumental impact in reducing healthcare expenditures and improving the quality of life of older adults.

Interventions

OTHERMRI Neuroimaging

MRI scans utilized to measure the structural and functional integrity of the brain.

OTHERQuantitative Sensory Testing

Vibratory Detection Thresholds; Tactile Detection Thresholds; Thermal Detection Thresholds, Pain Thresholds, and Temporal Summation; Allodynia and Temporal Summation; Punctate Pain Testing and Temporal Summation; and Pressure Pain Thresholds.

OTHERQuestionnaires

The Modified Mini-Mental State Examination (3MS), the Montreal Cognitive Assessment (MoCA), the Center for Epidemiologic Studies Depression Scale (CES-D), the Geriatric Depression Scale (GDS), the Edinburg Handedness Inventory, the Ten-Item Personality Inventory (TIPI), the Pittsburgh Sleep Quality Index (PSQI), the state and trait versions of the State-Trait Anxiety Inventory (STAI), the state and trait versions of the Positive and Negative Affect Schedule (PANAS), pain questionnaires (the Graded Chronic Pain Scale (GCPS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Pain-Detect, the short-form McGill Pain Questionnaire (SF-MPQ-2), and the Coping Strategies Questionnaire-Revised (CSQ-R)), a standardized paper and pencil cognitive battery (Hopkins Verbal Learning Test (HVLT), Trail Making A&B, Boston Naming Test, Controlled Oral Word Association Test (COWAT), Stroop Interference Test, Ruff Figural Fluency Test, and Raven's Progressive Matrices Test).

OTHERPhysical and Cognitive Function Testing

Upper Limb Isometric Strength, Short Physical Performance Battery (SPPB), GAITRite Instrumented Walking, Galvanic Skin Response, Knee Extension Isokinetic Strength, the Pepper Assessment Tool for Disability (PAT-D), and an electronic NIH Toolbox Cognitive Battery.

Sponsors

National Institute on Aging (NIA)
CollaboratorNIH
National Institutes of Health (NIH)
CollaboratorNIH
University of Florida
Lead SponsorOTHER

Study design

Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes

Inclusion criteria

* older adults over 60 years of age with and without musculoskeletal pain * healthy young adults between the ages of 18-25

Exclusion criteria

* pregnant women * history of alcohol/drug abuse in the past * known intra-cerebral pathology or epilepsy * significant cognitive impairment as evidenced by the 3MS * hospitalizations for mental health reasons in the past year * not meeting MRI screening requirements (implants, prosthesis, artificial limb/joint, shunt, metal rods, hearing aid, claustrophobia or anxiety) * chronic/current use of narcotic medications * serious systemic (uncontrolled diabetes; self reported A1C\>7), neurological , or cardiovascular disease (uncontrolled hypertension \>155/90) * liver or kidney disease * inability to consent for study participation

Design outcomes

Primary

MeasureTime frameDescription
Short Physical Performance Battery (SPPB)At baseline-physical function visitThe Short Physical Performance Battery (SPPB) Total Score is a measure of physical function. It is calculated by summing three measures of lower-extremity function: standing balance (side-by-side, semi-tandem, and tandem stance), 4-meter walking speed, and ability to rise from a chair. Each task is rated on a 0-4 scale, with increasing scores indicating better physical performance. The SPPB Total scores range from 0-12.

Countries

United States

Participant flow

Participants by arm

ArmCount
Older Adults With Musculoskeletal Pain
Older adults (60+ years old) experiencing musculoskeletal pain will undergo: MRI Neuroimaging, Quantitative Sensory Testing, Physical and Cognitive Function Testing, and questionnaire batteries.
53
Older Adults Without Musculoskeletal Pain
Older adults (60+ years old) not experiencing musculoskeletal pain will undergo: MRI Neuroimaging, Quantitative Sensory Testing, Physical and Cognitive Function Testing, and questionnaire batteries.
22
Young Controls
Healthy young adults (18-25 years old) not experiencing musculoskeletal pain will undergo: MRI Neuroimaging, Quantitative Sensory Testing, Physical and Cognitive Function Testing, and questionnaire batteries.
30
Total105

Baseline characteristics

CharacteristicOlder Adults With Musculoskeletal PainOlder Adults Without Musculoskeletal PainYoung ControlsTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
53 Participants22 Participants0 Participants75 Participants
Age, Categorical
Between 18 and 65 years
0 Participants0 Participants30 Participants30 Participants
Race/Ethnicity, Customized
Race/Ethnicity
African American
5 Participants0 Participants1 Participants6 Participants
Race/Ethnicity, Customized
Race/Ethnicity
Asian
0 Participants0 Participants3 Participants3 Participants
Race/Ethnicity, Customized
Race/Ethnicity
Caucasian
46 Participants22 Participants17 Participants85 Participants
Race/Ethnicity, Customized
Race/Ethnicity
Hispanic
1 Participants0 Participants7 Participants8 Participants
Race/Ethnicity, Customized
Race/Ethnicity
Pacific Islander
1 Participants0 Participants2 Participants3 Participants
Region of Enrollment
United States
53 participants22 participants30 participants105 participants
Sex: Female, Male
Female
35 Participants10 Participants16 Participants61 Participants
Sex: Female, Male
Male
18 Participants12 Participants14 Participants44 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 530 / 220 / 30
other
Total, other adverse events
2 / 530 / 220 / 30
serious
Total, serious adverse events
0 / 530 / 220 / 30

Outcome results

Primary

Short Physical Performance Battery (SPPB)

The Short Physical Performance Battery (SPPB) Total Score is a measure of physical function. It is calculated by summing three measures of lower-extremity function: standing balance (side-by-side, semi-tandem, and tandem stance), 4-meter walking speed, and ability to rise from a chair. Each task is rated on a 0-4 scale, with increasing scores indicating better physical performance. The SPPB Total scores range from 0-12.

Time frame: At baseline-physical function visit

ArmMeasureValue (MEAN)Dispersion
Older Adults With Musculoskeletal PainShort Physical Performance Battery (SPPB)10.95 score on a scaleStandard Deviation 1.1
Older Adults Without Musculoskeletal PainShort Physical Performance Battery (SPPB)10.82 score on a scaleStandard Deviation 1.87
Young ControlsShort Physical Performance Battery (SPPB)11.75 score on a scaleStandard Deviation 0.64
Comparison: H0: mean(SPPB\_older\_pain) = mean(SPPB\_older\_no pain) = mean(SPPB\_younger)p-value: 0.0561ANOVA

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026