Brain Biomarker of Endogenous Analgesia in Patients With Chronic Knee Pain

Brain Biomarker of Endogenous Analgesia in Patients With Chronic Knee Pain

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.

The objective of this study is to identify the neural correlates of central nervous system (CNS) pain inhibition in patients with knee osteoarthritis (OA) and determine how the correlates relate to clinical chronic (i.e., greater than 6 months) knee pain. To attain this objective, the investigators will test the following working hypotheses: (H1) in knee OA patients with moderate osteoarthritis but severe knee pain, cortical correlates of CNS pain inhibition are diminished compared to patients with less knee pain and (H2) provocation of clinical knee pain with ambulation produces greater pain-related cortical activation in patients with greater clinical knee pain at baseline. The study will also compare patients with knee OA to a control group to test the hypothesis (H3) that CNS pain inhibition behavioral and functional near-infrared spectroscopy (fNIRS) brain imaging measures are diminished in knee OA. Finally, in exploratory analysis, the investigators hypothesize that cortical functional connectivity is altered in patients with greater knee pain.

The study approach is to measure brain activity in patients with knee osteoarthritis, divided into high pain intensity and low pain intensity groups, and in pain-free controls with fNIRS scanning during rest, quantitative sensory testing (QST) measures of CNS pain inhibition (conditioned pain modulation and offset analgesia), and walking and stair climbing tasks. The rationale is that successful completion of this study will determine whether fNIRS measures relate to QST measures of CNS pain inhibition and clinical pain intensity both at rest and during activity. This fundamental knowledge, in combination with prior studies of conditioned pain modulation (CPM), will be important to understanding how CNS pain inhibition may contribute to a range of chronic pain syndromes.

Inclusion Criteria:

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

Exclusion Criteria:

1. Inflammatory arthritis (e.g. rheumatoid arthritis)
2. Inability to walk and climb stairs unassisted
3. History of knee replacement or open knee surgery
4. History of arthroscopic knee surgery within the last 3 months (>3 months does not exclude participant)
5. History of knee radiofrequency nerve ablation or ligation
6. Current opioid use
7. 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
8. Cognitive impairment affecting the ability to provide informed consent, understand directions, and participate in study procedures
9. Uncontrolled or unstable medical disorder preventing participation in study procedures
10. History of brain surgery
11. Tattoos on forearm or knee
12. Pregnancy
13. Patients with chronic pain conditions that are more severe than their knee arthritis pain (e.g., CRPS, fibromyalgia)
14. Patients whose most painful knee is excluded for another reason (e.g., recent surgery on most painful knee)
15. For the pain-free control group: a history of chronic pain
16. History of intra-articular steroid injections, platelet enriched or hyaluronic acid injections in the last 1 month