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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.
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| 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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Patients who visit Seoul National University Bundang Hospital for two-staged bilateral total knee arthroplasty.
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| Name | Affiliation | Role |
|---|---|---|
| Jin-Woo Park, MD | Seoul National University Bundang Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Seoul National University Bundang Hospital | Seongnam-si | Gyeonggi-do | 13620 | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22843792 | Background | Losina E, Katz JN. Total knee replacement: pursuit of the paramount result. Rheumatology (Oxford). 2012 Oct;51(10):1735-6. doi: 10.1093/rheumatology/kes199. Epub 2012 Jul 28. No abstract available. | |
| 18269385 | Background | Rosseland LA, Solheim N, Stubhaug A. Pain and disability 1 year after knee arthroscopic procedures. Acta Anaesthesiol Scand. 2008 Mar;52(3):332-7. doi: 10.1111/j.1399-6576.2007.01541.x. |
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| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
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The Saliva in which the concentrations of cortisol and DHEA will be measured and analyzed for correlation between concentration-related changes and postoperative knee pain variations.
| 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 |
| 14659522 | Background | Harden NR, Bruehl S, Stanos S, Brander V, Chung OY, Saltz S, Adams A, Stulberg DS. Prospective examination of pain-related and psychological predictors of CRPS-like phenomena following total knee arthroplasty: a preliminary study. Pain. 2003 Dec;106(3):393-400. doi: 10.1016/j.pain.2003.08.009. |
| 9416776 | Background | Pruessner JC, Wolf OT, Hellhammer DH, Buske-Kirschbaum A, von Auer K, Jobst S, Kaspers F, Kirschbaum C. Free cortisol levels after awakening: a reliable biological marker for the assessment of adrenocortical activity. Life Sci. 1997;61(26):2539-49. doi: 10.1016/s0024-3205(97)01008-4. |
| 23994101 | Result | Kim MH, Nahm FS, Kim TK, Chang MJ, Do SH. Comparison of postoperative pain in the first and second knee in staged bilateral total knee arthroplasty: clinical evidence of enhanced pain sensitivity after surgical injury. Pain. 2014 Jan;155(1):22-27. doi: 10.1016/j.pain.2013.08.027. Epub 2013 Aug 30. |
| 28077538 | Result | Shin HJ, Kim EY, Na HS, Kim TK, Kim MH, Do SH. Magnesium sulphate attenuates acute postoperative pain and increased pain intensity after surgical injury in staged bilateral total knee arthroplasty: a randomized, double-blinded, placebo-controlled trial. Br J Anaesth. 2016 Oct;117(4):497-503. doi: 10.1093/bja/aew227. Epub 2016 Oct 17. |
| 27082645 | Result | Jo KB, Lee YJ, Lee IG, Lee SC, Park JY, Ahn RS. Association of pain intensity, pain-related disability, and depression with hypothalamus-pituitary-adrenal axis function in female patients with chronic temporomandibular disorders. Psychoneuroendocrinology. 2016 Jul;69:106-15. doi: 10.1016/j.psyneuen.2016.03.017. Epub 2016 Mar 31. |
| 22445364 | Result | Park JY, Ahn RS. Hypothalamic-pituitary-adrenal axis function in patients with complex regional pain syndrome type 1. Psychoneuroendocrinology. 2012 Sep;37(9):1557-68. doi: 10.1016/j.psyneuen.2012.02.016. Epub 2012 Mar 24. |
| 36037793 | Derived | Ahn RS, Park JW, Park IS, Shin HJ, Ryu JH, Oh AY, Park HY, Do SH. The Involvement of the Hypothalamus-Pituitary-Adrenal Axis in the Development of Hyperalgesia during the Early Postoperative Period. Neuroendocrinology. 2023;113(3):319-331. doi: 10.1159/000526793. Epub 2022 Aug 29. |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |