Brain Biomarker of Endogenous Analgesia in Patients With Chronic Knee Pain

NCT05003323 | Completed

• 1 other identifier: STUDY20060254
• Study Type: observational
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

This case-control study in patients with knee osteoarthritis and pain-free control individuals aims to develop a brain biomarker of endogenous analgesia that may be used in subsequent clinical trials. Deficits in central nervous system (CNS) pain inhibition may contribute to chronic pain intensity, but quantitative sensory testing (QST) methods are limited. Incorporating brain imaging to assessments of CNS pain inhibition, by examining activity in relevant brain networks, would allow for an objective, physiologic measure of CNS pain inhibition. Preliminary data in pain-free volunteers implicate cortical activity measured with functional near-infrared spectroscopy (fNIRS) during CNS pain inhibition. Broadly, the investigators hypothesize that variability in CNS pain inhibition contributes to variability in clinical pain intensity.

Conditions

Chronic Pain; Chronic Knee Pain; Knee Osteoarthritis; Analgesia

Outcome Measures

Primary Outcomes (4)

• Differences in offset analgesia

  Pain intensity difference during offset and control heat stimuli

  15 minutes

• Differences in brain region activation- QST

  Difference in brain region activation (as measured by oxygenated hemoglobin, HbO) between CNS inhibition and control stimuli during QST procedures.

  2-3 hours

• Differences in brain region activation- walking test

  Change in brain region activation (HbO) between rest and ambulation during the 6 minute walking test test

  15 minutes

• Differences in brain region activation- stair climbing

  Change in brain region activation (HbO) between rest and ambulation during the stair climbing test

  15 minutes

Secondary Outcomes (19)

• Differences in resting fNIRS signaling

  5-10 minutes

• QST battery responses

  2-3 hours

• Pain intensity scores after stair climbing task

  10 minutes

• Pain intensity scores after walking test

  6 minutes

• Duration of stair climbing task

  10 minutes

Study Arms (3)

High Knee Pain with Osteoarthritis

Adults 45-80 years old who have moderately severe knee osteoarthritis and rate their daily knee pain at \>=6 on a 0-10 numeric rating scale

Low Knee Pain with Osteoarthritis

Adults 45-80 who have moderately severe knee osteoarthritis and rate their daily knee pain at \<=5 on a 0-10 numeric rating scale

Healthy Controls

Age matched, BMI matched adults who do not have knee osteoarthritis or chronic pain

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from the Pitt+Me registry which comprises of any members of the local population who are registered in the program.

You may qualify if:

• For the knee arthritis groups: Chronic knee pain with evidence of knee osteoarthritis - radiographically grades 2-4
• Age: 45-80 years old
• Gender: Males and females will be recruited.
• Language: only English-speaking subjects will be included.

You may not qualify if:

• Inflammatory arthritis (e.g. rheumatoid arthritis)
• Inability to walk and climb stairs unassisted
• History of knee replacement or open knee surgery
• History of arthroscopic knee surgery within the last 3 months (\>3 months does not exclude participant)
• History of knee radiofrequency nerve ablation or ligation
• Current opioid use
• Current use of antidepressants that are not in the serotonin-selective reuptake inhibitor (SSRI) class. Patients who are currently using an SSRI are allowed to take part in the study
• 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
• History of brain surgery
• Tattoos on forearm or knee
• Pregnancy
• Patients with chronic pain conditions that are more severe than their knee arthritis pain (e.g., CRPS, fibromyalgia)
• Patients whose most painful knee is excluded for another reason (e.g., recent surgery on most painful knee)
• For the pain-free control group: a history of chronic pain

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

UPMC Pain Medicine at Centre Commons

Pittsburgh, Pennsylvania, 15206, United States

Location

Related Publications (1)

• Alter BJ, Maurer M, O'Connell B, Sanchez AG, Kaynar AM, DiGioia AM, Huppert T, Wasan AD. Deficits in temporal pain inhibition are associated with greater pain and functional impairment in osteoarthritis. Pain. 2025 Nov 1;166(11):2490-2509. doi: 10.1097/j.pain.0000000000003648. Epub 2025 Jun 19.

  PMID: 40539481 DERIVED

MeSH Terms

Conditions

Chronic Pain; Osteoarthritis, Knee; Agnosia

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Study Officials

• Benedict Alter, MD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 6, 2021
• First Posted: August 12, 2021
• Study Start: November 18, 2021
• Primary Completion: October 20, 2023
• Study Completion: October 20, 2023
• Last Updated: January 13, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)