The Relationship Between Chronic OA Pain and Cognition Deficits in OA Patients.

Study Overview
=================
Brief Summary
-----------------
The goal of this observational study is to learn about the association between pain characteristics and cognitive functions in chronic knee osteoarthritis. The main questions it aims to answer are: If pain characteristics affect cognitive functions in severe knee OA patients? If concentration of neuroinflammation mediators were raised in severe knee OA patients with comparing with control group participants? Participants will receive pain and cognition questionnaire before surgery and their blood and CSF will be collected for further analysis of neuroinflammation mediators.

Detailed Description
-----------------
In the previous studies, which revealed that because neural systems involved in cognition and pain processing are closely linked, they may affect with each other. In addition to sensory symptoms, cognitive functioning is thought to be affected in chronic pain patients. Pain uses cognitive resources, alters neural plasticity and affects expression and activity of a variety of chemical and cellular neuromediators. There are several brain regions such as amygdala and hippocampus which are most commonly activated during pain processing.Osteoarthritis (OA) of the knee is one of the leading causes of disability among noninstitutionalized elderly adults. One population-based study revealed that osteoarthritis increases the risk of cognitive deficits diseases such as dementia. However the possible mechanism had not be elucidated. Recent study revealed that OA-induced hyperalgesia was associated with increased nerve growth factor (NGF)/tropomycin receptor kinase A (TrkA) signaling. NGF activation of extracellular signal-regulated kinase (ERK)/ mitogen-activated protein kinase (MAPK) may play a role in centralization of OA pain. Otherwise NGF has also been shown to produce a dramatic upregulation of brain-derived neurotrophic factor (BDNF) in trkA-expressing dorsal root ganglion (DRG) cells, and there is now growing evidence that BDNF may serve as a central regulator of excitability and is a neuromodulate or of central pain processing. On the other hand, in previous studies they showed that BDNF plays a critical role in synaptic plasticity, memory processes and storage of long-term memory. The BDNF/tropomycin receptor kinase B (TrkB) system in the hippocampus plays a crucial role not only in the memory acquisition, but also in the retention and / or recall of spatial memory. Besides ongoing pain in chronic knee OA is characterized by increased brain activity in limbic-affective regions thus providing novel evidence for a strong emotional component of arthritis pain. There are feedback loops exist between pain, emotion and cognition. How is the role of BDNF in such loop? The objective of the study was the evaluation of association between pain characteristics and cognitive functions in severe knee OA patients. Besides, we will try to explore the possible mechanisms by which chronic OA like pain develops to cognitive deficits in animal models. The relationship between BDNF levels in body fluids (serum and CSF) and pain characteristics and cognitive function was also evaluated in the whole sample.

Official Title
-----------------
The Relationship Between Chronic OA Pain and Cognition Deficits in OA Patients.

Conditions
-----------------
Knee Osteoarthritis, Neuroinflammatory Response

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: OA patients who were scheduled to receive elective surgery which need spinal anesthesia. Age is more than 20 years old. American Society of Anesthesiologists (ASA) class I-III. Exclusion Criteria: Unwilling to participate. Age is lesser than 20 years old. Autoimmune diseases. Previous knee injury or infection history. Brain region disease ex: stroke or brain tumor...etc. Mild cognitive impairment, dementia or other neurodegenerative diseases. Cancer. With other chronic pain.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 86 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| OA group<br>Knee osteoarthritis patients who were scheduled to receive elective total knee replacement surgery which need spinal anesthesia. | |
| Control group<br>Control group patients were scheduled to receive elective general surgery or urological surgery with spinal anesthesia. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Western Ontario and McMaster universities Osteoarthritis Index (WOMAC) | The WOMAC questionnaire has been used to assess subjects with OA of the hip or knee and consists of 24 items divided into 3 subscales: self-perception of pain (5 items), joint stiffness (2 items), and functional performance (17 items) during the previous 72 h. | The WOMAC questionnaire were measured on the day before their surgery. | 
| The cognitive abilities screening instrument (CASI) | The CASI has been commonly used in dementia research and clinical practice to evaluate a subject's cognitive abilities. | The CASI questionnaire were measured on the day before their surgery. | 
| Glia mediators of neuroinflammation | Glia mediators of neuroinflammation include interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF α), BDNF and fractalkine. | All blood and CSF samples were obtained before spinal anesthesia. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The geriatric depression scale (GDS-15) | The GDS-15 was used for evaluation of emotion especially for participant of age > 65. years old. | The GDS-15 questionnaire were measured on the day before their surgery. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic pain, Knee osteoarthritis, Cognitive deficits