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The aim of this observational study is to investigate the relationship between pain severity and alterations in bone-derived and brain-derived signaling molecules (including serum neurotransmitters and inflammatory cytokines), as well as structural and functional changes in the ventrolateral periaqueductal gray (vlPAG) region in patients with kidney-deficiency type knee osteoarthritis (KOA). The central question it seeks to address is whether changes in these signaling molecules and vlPAG alterations are associated with the degree of pain.
Patients scheduled to undergo total knee arthroplasty (TKA) due to KOA will be enrolled prior to surgery. Before the operation, they will undergo questionnaire assessments, physical examinations, imaging evaluations, and blood sample collection. The resected tibial plateau tissue obtained during surgery will be used for subsequent laboratory analyses.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| KOA | Patients with knee osteoarthritis of renal deficiency type who meet the diagnostic criteria | ||
| HC | Healthy volunteers |
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| Measure | Description | Time Frame |
|---|---|---|
| Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index | The WOMAC Index is a validated instrument used to assess pain, stiffness, and physical dysfunction in patients with osteoarthritis. It comprises 3 subscales with a total of 24 items, yielding a total score ranging from 0 to 96, where higher scores indicate more severe symptoms and greater functional impairment. | Participants were tested immediately after being included in the study. |
| Measure | Description | Time Frame |
|---|---|---|
| Visual Analog Scale (VAS) score | The VAS score is a subjective measure used to assess pain intensity, typically presented as a continuous scale ranging from 0 to 10, with higher scores indicating greater pain severity. | Participants were tested immediately after being included in the study. |
| Pattern Element Analysis |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with knee osteoarthritis of kidney deficiency type from the Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine. And the healthy volunteers recruited by the research team.
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Tibial plateau samples obtained from KOA patients during total knee arthroplasty.
A pattern differentiation system would be used to assess the severity of kidney-deficiency-related pathological changes. |
| Participants were tested immediately after being included in the study. |
| Function of Knee Joint | Gait analysis and neutral position (0°) method to evaluate knee joint function. | Participants were tested immediately after being included in the study. |
| Volume of Subchondral Cystic Lesions | Knee MRI combined with Mimics software would be used to calculate the volume of subchondral cystic lesions. | Participants were tested immediately after being included in the study. |
| Brain Region Structure | Diffusion Tensor Imaging (DTI) would be employed to investigate microstructural alterations in the vlPAG by assessing the diffusion properties of water molecules, thereby reflecting the integrity and connectivity of white matter tracts. | Participants were tested immediately after being included in the study. |
| Brain Region Functional Connection | Resting-state functional magnetic resonance imaging (fMRI) would be used to investigate alterations in functional connectivity of the vlPAG. | Participants were tested immediately after being included in the study. |
| Serum Neurotransmitters | Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) would be employed to detect changes in serum levels of excitatory and inhibitory neurotransmitters. | Participants were tested immediately after being included in the study. |
| Serum Inflammatory Cytokines | Serum levels of inflammatory cytokines would be measured using the Luminex multiplex liquid-phase assay. | Participants were tested immediately after being included in the study. |
| Microarchitecture of Subchondral Bone | Following TKA surgery, the resected tibial plateau would be collected for further analysis. Micro-computed tomography (micro-CT) would be employed to assess differences in subchondral bone microarchitecture between load-bearing and non-load-bearing regions | One day following TKA surgery. |
| Morphological Differences of Cartilage and Subchondral | Hematoxylin and eosin (HE) staining would be used to examine the morphological differences in cartilage and subchondral bone between the load-bearing and non-load-bearing regions of the tibial plateau. | One month following TKA surgery. |
| Subchondral Bone Osteoclast Activity | Tartrate-resistant acid phosphatase (TRAP) staining would be used to assess osteoclast activity in the subchondral bone of load-bearing and non-load-bearing regions. | One month following TKA surgery. |
| Subchondral Bone Osteoblastic Activity | Alkaline phosphatase (ALP) staining would be used to assess osteoblastic activity in the subchondral bone of load-bearing and non-load-bearing regions. | One month following TKA surgery. |
| Subchondral Bone Sensory Nerve Fiber Distribution | Karnovsky-Roots staining would be used to assess the distribution of sensory nerve fibers in the subchondral bone of load-bearing and non-load-bearing regions. | One month following TKA surgery. |
| Pain-Sensitization-Related Factors in Subchondral Bone | Immunofluorescence staining would be used to evaluate changes in pain-sensitization-related regulatory factors in the subchondral bone (SPP1, Netrin1, TMEM119, PGE2, EP4) of load-bearing and non-load-bearing regions. | One month following TKA surgery. |
| Subchondral Bone Osteoclast Marker | Immunofluorescence staining would be used to detect changes in osteoclast marker proteins (TRAP, CTSK) in the subchondral bone of load-bearing and non-load-bearing regions. | One month following TKA surgery. |
| Subchondral Bone Nociceptor Distribution | Immunofluorescence staining would be used to detect changes in nociceptor marker proteins (TRPV1, TRPA1, CGRP, TrkA, NF200) in the subchondral bone of load-bearing and non-load-bearing regions. | One month following TKA surgery. |