The 'Bone-Brain' Crosstalk Mechanism of Subchondral Bone Nociceptive Sensitization Activating SPP1-Positive Microglia in the vlPAG Region Elucidates the Theoretical Connotation of Treating Knee Osteoarthritis Based on Kidney Differentiation

The 'Bone-Brain' Crosstalk Mechanism of Subchondral Bone Nociceptive Sensitization Activating SPP1-Positive Microglia in the vlPAG Region Elucidates the Theoretical Connotation of Treating Knee Osteoarthritis Based on Kidney Differentiation

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.

Inclusion Criteria:

• Clinical diagnosis of KOA
• Age between 60-70 years.
• Kellgren-Lawrence grade IV on anteroposterior and lateral knee X-rays.
• Scheduled for total knee arthroplasty.
• Voluntarily signs informed consent.

Exclusion Criteria:

• Clinical diagnosis of ankylosing spondylitis, rheumatoid arthritis, gout, or other related conditions.
• Presence of metabolic bone diseases, acute trauma, malignancies, infections, or other complications severely affecting knee function.
• Use of drugs affecting bone metabolism (e.g., corticosteroids, zoledronic acid) within the past 6 months.
• Presence of psychiatric disorders or serious cardiovascular, pulmonary, renal, hepatic, hematologic, or other systemic diseases.
• Contraindications to MRI.