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

Knee Osteoarthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05570240
• Other study ID #: VGHKS19-CT2-21
• Status: Completed
• Start date: August 7, 2019
• Est. completion date: April 22, 2021

Study information

• Verified date: October 2022
• Source: Kaohsiung Veterans General Hospital.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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:

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 22, 2021
• Est. primary completion date: April 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 86 Years

Eligibility

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.

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Neuroinflammatory Response
• Osteoarthritis
• Osteoarthritis, Knee

Locations

Country	Name	City	State
Taiwan	Kaohsiung Veterans General Hopital	Kaohsiung city	Zuoying Dist

Sponsors (1)

Lead Sponsor	Collaborator
Kaohsiung Veterans General Hospital.

Country where clinical trial is conducted

Taiwan, 

References & Publications (12)

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. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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- — View Citation

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.202 — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010 Aug;26(3):355-69. doi: 10.1016/j.cger.2010.03.001. Review. Erratum in: Clin Geriatr Med. 2013 May;29(2):ix. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	Glia mediators of neuroinflammation	Glia mediators of neuroinflammation include interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor a (TNF a), BDNF and fractalkine.	All blood and CSF samples were obtained before spinal anesthesia.
Secondary	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.