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

NCT ID: NCT05570240

Last Updated: 2022-10-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-08-07

Study Completion Date

2021-04-22

Brief Summary

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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:

1. If pain characteristics affect cognitive functions in severe knee OA patients?
2. 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

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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.

Conditions

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Knee Osteoarthritis Neuroinflammatory Response

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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OA group

Knee osteoarthritis patients who were scheduled to receive elective total knee replacement surgery which need spinal anesthesia.

No interventions assigned to this group

Control group

Control group patients were scheduled to receive elective general surgery or urological surgery with spinal anesthesia.

No interventions assigned to this group

Eligibility Criteria

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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.
Minimum Eligible Age

20 Years

Maximum Eligible Age

86 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kaohsiung Veterans General Hospital.

OTHER

Sponsor Role lead

Responsible Party

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Chun-Hsien Wen

Physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Chun-Hsien Wen, Physician

Role: PRINCIPAL_INVESTIGATOR

Kaohsiung Veterans General Hospital.

Chen-Hsiu Chen, Physician

Role: STUDY_DIRECTOR

Kaohsiung Veterans General Hospital.

Yuan-Yi Chia, Director

Role: STUDY_DIRECTOR

Kaohsiung Veterans General Hospital.

Chih-Chi Tsai, RA

Role: STUDY_CHAIR

Kaohsiung Veterans General Hospital.

Locations

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Kaohsiung Veterans General Hopital

Kaohsiung City, Zuoying Dist, Taiwan

Site Status

Countries

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Taiwan

References

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Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010 Aug;26(3):355-69. doi: 10.1016/j.cger.2010.03.001.

Reference Type RESULT
PMID: 20699159 (View on PubMed)

Kyrkanides S, Tallents RH, Miller JN, Olschowka ME, Johnson R, Yang M, Olschowka JA, Brouxhon SM, O'Banion MK. Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice. J Neuroinflammation. 2011 Sep 7;8:112. doi: 10.1186/1742-2094-8-112.

Reference Type RESULT
PMID: 21899735 (View on PubMed)

Huang SW, Wang WT, Chou LC, Liao CD, Liou TH, Lin HW. Osteoarthritis increases the risk of dementia: a nationwide cohort study in Taiwan. Sci Rep. 2015 May 18;5:10145. doi: 10.1038/srep10145.

Reference Type RESULT
PMID: 25984812 (View on PubMed)

Li X, Tong Q, Gao J, Liu C; Alzheimer's Disease Neuroimaging Initiative; Liu Y. Osteoarthritis Was Associated With a Faster Decline in Hippocampal Volumes in Cognitively Normal Older People. Front Aging Neurosci. 2020 Aug 14;12:190. doi: 10.3389/fnagi.2020.00190. eCollection 2020.

Reference Type RESULT
PMID: 32922280 (View on PubMed)

Wu L, Wang X, Ye Y, Liu C. Association of Osteoarthritis With Changes in Structural Neuroimaging Markers Over Time Among Non-demented Older Adults. Front Aging Neurosci. 2021 Aug 10;13:664443. doi: 10.3389/fnagi.2021.664443. eCollection 2021.

Reference Type RESULT
PMID: 34447303 (View on PubMed)

Clark AK, Malcangio M. Fractalkine/CX3CR1 signaling during neuropathic pain. Front Cell Neurosci. 2014 May 7;8:121. doi: 10.3389/fncel.2014.00121. eCollection 2014.

Reference Type RESULT
PMID: 24847207 (View on PubMed)

Grace PM, Hutchinson MR, Maier SF, Watkins LR. Pathological pain and the neuroimmune interface. Nat Rev Immunol. 2014 Apr;14(4):217-31. doi: 10.1038/nri3621. Epub 2014 Feb 28.

Reference Type RESULT
PMID: 24577438 (View on PubMed)

Montague K, Malcangio M. The therapeutic potential of targeting chemokine signalling in the treatment of chronic pain. J Neurochem. 2017 May;141(4):520-531. doi: 10.1111/jnc.13927. Epub 2017 Feb 24.

Reference Type RESULT
PMID: 27973687 (View on PubMed)

Subbarayan MS, Joly-Amado A, Bickford PC, Nash KR. CX3CL1/CX3CR1 signaling targets for the treatment of neurodegenerative diseases. Pharmacol Ther. 2022 Mar;231:107989. doi: 10.1016/j.pharmthera.2021.107989. Epub 2021 Sep 4.

Reference Type RESULT
PMID: 34492237 (View on PubMed)

Cappoli N, Tabolacci E, Aceto P, Dello Russo C. The emerging role of the BDNF-TrkB signaling pathway in the modulation of pain perception. J Neuroimmunol. 2020 Dec 15;349:577406. doi: 10.1016/j.jneuroim.2020.577406. Epub 2020 Sep 24.

Reference Type RESULT
PMID: 33002723 (View on PubMed)

Malfait AM, Miller RE, Block JA. Targeting neurotrophic factors: Novel approaches to musculoskeletal pain. Pharmacol Ther. 2020 Jul;211:107553. doi: 10.1016/j.pharmthera.2020.107553. Epub 2020 Apr 18.

Reference Type RESULT
PMID: 32311372 (View on PubMed)

Tang J, Bair M, Descalzi G. Reactive Astrocytes: Critical Players in the Development of Chronic Pain. Front Psychiatry. 2021 May 28;12:682056. doi: 10.3389/fpsyt.2021.682056. eCollection 2021.

Reference Type RESULT
PMID: 34122194 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Other Identifiers

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VGHKS19-CT2-21

Identifier Type: -

Identifier Source: org_study_id

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