Central Sensitization and Alteration of Circulating Neurosteroid

Pain, Postoperative Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03298711
• Other study ID #: B-1709-423-308
• Status: Completed
• Start date: November 20, 2017
• Est. completion date: May 6, 2020

Study information

• Verified date: October 2020
• Source: Seoul National University Bundang Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: May 6, 2020
• Est. primary completion date: May 6, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthroplasty, Replacement, Knee
• Pain, Postoperative

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Bundang Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (8)

Harden RN, Bruehl S, Stanos S, Brander V, Chung OY, Saltz S, Adams A, Stulberg SD. 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. — View Citation

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. — View Citation

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):22-7. doi: 10. — View Citation

Losina E, Katz JN. Total knee replacement: pursuit of the paramount result. Rheumatology (Oxford). 2012 Oct;51(10):1735-6. Epub 2012 Jul 28. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. B — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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	Analgesic usage (PCA)	Fentanyl usage with PCA	At 24h and 48h after the operation, for each stage of the operation.
Secondary	Analgesic usage (rescue)	The number of rescue analgesics treatments	At 24h and 48h after the operation, for each stage of the operation.
Secondary	Antiemetic usage	The number of antiemetics treatments	At 24h and 48h after the operation, for each stage of the operation.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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