Central Sensitization and Alteration of Circulating Neurosteroid

Study Overview
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Brief Summary
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For patients who underwent two-stage replacement of both knee joints (one knee surgery - one week term- the other knee surgery), postoperative pain and analgesic usage with patient-controlled analgesia (PCA) increased at the second stage, which suggests that central sensitization occurs within a short period (one week) in patients who undergo total knee arthroplasty (TKA). Neurosteroids act on NMDA and AMPA receptors, GABAa receptors, and voltage-dependent Ca2+ or K+ channels of sensory neurons to increase invasive or neuropathic pain and, conversely, to exhibit analgesic and anticonvulsant effects. These actions mean that the neurosteroid acts as an endogenous regulator of pain control and central sensitization. The purpose of this study is to confirm that the hypothalamus-pituitary-adrenal (HPA) axis, which is the main body of endocrine neurosteroid, is associated with increased pain sensitivity after TKA. The concentrations of cortisol and dehydroepiandrosterone (DHEA) in the saliva of patients who undergo two-staged bilateral knee replacement surgery (one knee surgery - one week term- the other knee surgery) will be measured at each stage and analyzed for correlation between concentration-related changes of HPA and postoperative knee pain variations.

Official Title
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Relationship Between Central Sensitization and Alteration of Circulating Neurosteroid Following Bilateral Total Knee Arthroplasty

Conditions
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Arthroplasty, Replacement, Knee, Pain, Postoperative

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Two-staged bilateral total knee arthroplasty (one knee - one week - the other knee) American Society of Anesthesiologists (ASA) class I, II Postmenopausal women aged under 71 Exclusion Criteria: Patients who have used analgesics before surgery, such as chronic pain patients ≥ ASA class III, including patients with renal impairment or symptomatic cardiovascular disease Patients who refuse to participate in the study or from whom receive informed consent cannot be received.

Ages Eligible for Study
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Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The profiles of cortisol in the saliva | The cortisol concentrations in the saliva, at the evening before the operation (21:00-22:00), just after wake-up in the morning of operation day, and 30 and 60 minutes after the wake-up. | From the evening (9PM) before the operation day to the morning (60 minutes after the wake-up) of the operation day, for each stage of the operation. | 
| The profiles of DHEA in the saliva | The DHEA concentrations in the saliva, at the evening before the operation (21:00-22:00), just after wake-up in the morning of operation day, and 30 and 60 minutes after the wake-up. | From the evening (9PM) before the operation day to the morning (60 minutes after the wake-up) of the operation day, for each stage of the operation. | 
| Post operative knee pain | At rest and at maximum knee flexion, visual analogue scale (VAS) score of knee pain; | At 24h and 48h after the operation, for each stage of the operation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analgesic usage (PCA) | Fentanyl usage with PCA | At 24h and 48h after the operation, for each stage of the operation. | 
| Analgesic usage (rescue) | The number of rescue analgesics treatments | At 24h and 48h after the operation, for each stage of the operation. | 
| Antiemetic usage | The number of antiemetics treatments | At 24h and 48h after the operation, for each stage of the operation. | 
| Diurnal slope | slope for diurnal cortisol decline from the time point immediately upon awakening to nighttime | From the evening (9PM) before the operation day to the morning (60 minutes after the wake-up) of the operation day, for each stage of the operation. | 
| CARi | net increases in cortisol levels within the first 30 min after awakening | At the morning of operation day, for each stage of the operation | 
| CARauc | cortisol secretion area under the curve with respect to ground from the time point immediately after waking to 60 min after waking | At the morning of operation day, for each stage of the operation | 
| Daucawk | DHEA secretion area under the curve with respect to ground from the time point immediately after waking to 60 min after waking | At the morning of operation day, for each stage of the operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Central Nervous System Sensitization, Neuropeptides