Central Sensitization and Alteration of Circulating Neurosteroid

NCT03298711 | Completed

• 1 other identifier: B-1709-423-308
• Study Type: observational
• Target: 69
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Arthroplasty, Replacement, Knee; Pain, Postoperative

Keywords

Central Nervous System Sensitization; Neuropeptides

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (7)

• Analgesic usage (PCA)

  At 24h and 48h after the operation, for each stage of the operation.

• Analgesic usage (rescue)

  At 24h and 48h after the operation, for each stage of the operation.

• Antiemetic usage

  At 24h and 48h after the operation, for each stage of the operation.

• Diurnal slope

  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

  At the morning of operation day, for each stage of the operation

Eligibility Criteria

• Age: Up to 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients who visit Seoul National University Bundang Hospital for two-staged bilateral total knee arthroplasty.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Seoul National University Bundang Hospital: lead

Study Sites (1)

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Related Publications (9)

• 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.

  PMID: 22843792 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.

  PMID: 18269385 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.

  PMID: 14659522 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.

  PMID: 9416776 BACKGROUND

• 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.

  PMID: 23994101 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.

  PMID: 28077538 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.

  PMID: 27082645 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.

  PMID: 22445364 RESULT

• 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.

  PMID: 36037793 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

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.

MeSH Terms

Conditions

Pain, Postoperative

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Jin-Woo Park, MD

  Seoul National University Bundang Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 22, 2017
• First Posted: October 2, 2017
• Study Start: November 20, 2017
• Primary Completion: May 6, 2020
• Study Completion: May 6, 2020
• Last Updated: October 22, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)