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Kurien, Thomas (2018) Predicting chronic postoperative pain after total knee replacement surgery in patients with knee osteoarthritis. PhD thesis, University of Nottingham.

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Abstract

We hypothesise that preoperative pain characteristics in knee osteoarthritis (OA) patients may explain persistent pain after total knee replacement (TKR) surgery. Fifty patients awaiting TKR surgery and twenty-two asymptomatic healthy controls were recruited to evaluate the degree of neuropathic pain symptoms and central sensitisation of pain. OA patients were pain phenotyped into two groups based on the PainDETECT questionnaire: Group-A (scores ≥19) indicating neuropathic pain-like symptoms, Group-B (scores <19) indicating nociceptive or mixed pain. Controls were assigned to Group-C. Cuff algometry assessing pain detection thresholds (PDT) and pain tolerance (PTT) was conducted on the lower legs. Temporal summation of pain (TSP) was assessed using ten sequential cuff stimulations set at the subject's individual PTT and a von Frey stimulator. Conditioning pain modulation (CPM) was assessed by cuff pain conditioning on one leg and parallel assessment of PDT on the contralateral leg. Pressure pain thresholds (PPTs) were recorded by pressure handheld algometry local and distant to the knee. Knee pain intensity assessed using the visual analogue scale (VAS score (0-10cm) as well as questionnaires to assess knee function, depression, anxiety, pain catastrophizing and quality of life were collected before and 6 months post-TKR.

30% of knee OA patients demonstrated neuropathic pain-like symptoms (Group-A). Facilitated TSP and reduced PPTs distant to the knee were found in Group-A compared to Group-B and Group-C (p<0.001). Group-A had higher postoperative VAS scores than Group-B patients (p<0.0001) and facilitated TSP (p=0.022) compared with Group-C. Twenty-eight knee OA patients also agreed to undergo a BOLD functional brain MRI scan preoperatively and again six months post TKR to determine the neural signature of TSP using a novel cuff algometer applied to the gastrocnemius muscle ipsilateral to the arthritic knee. Seventeen age and sex matched healthy volunteers also agreed to be in this study for comparison. All subjects underwent a 3-Tesla knee MRI scan which was graded by 2 independent observers for bone marrow lesions (BMLs), Hoffa Synovitis and effusion synovitis using the MRI Osteoarthritis Knee Score (MOAKS). The OA patients also underwent a metal artefact reduction MRI knee scan six months post TKR to identify if there was a continued or new presence of BMLs, Hoffa-synovitis and effusion synovitis which may contribute to the development of chronic postoperative pain.

Our study has demonstrated that 30% of patients with knee OA listed for TKR surgery have neuropathic pain like symptoms. Patients with these symptoms report higher preoperative pain with longer pain duration, increased anxiety levels, poor knee function and lower quality of life measures prior to TKR surgery. The same patients respond less favourably to TKR surgery with significantly higher postoperative VAS pain scores, continued pain sensitization (lower PPTs, facilitated TSP and impaired CPM), scores, lower Oxford Knee Scores and quality of life. Increased neural brain activity in the somatosensory region S2 of the brain was found to be an imaging biomarker in central sensitization in knee OA patients. This neural activity is stimulated by chronic Hoffa-synovitis in the knee driving facilitation of the central integrative mechanisms of pain. Responders to TKR normalize their brain related activity with similar neural pattern to the healthy volunteers and show no evidence of central sensitization assessed using quantitative sensory testing (QST). Non-responders to TKR continue to report significant postoperative pain, lower Oxford Knee Scores, continued facilitated TSP, increased S2 neural brain activity along with postoperative BMLs and synovitis that may drive their postoperative pain. This thesis has identified the neural signature of TSP in knee OA patients and shown that brain related changes to TSP are maintained in patients with chronic postoperative pain after TKR. Preoperative identification of OA patients with central sensitization pain and subsequent pharmacological and behavioural therapy along with the eradication of painful BMLs and synovitis may significantly reduce the number of patients developing postoperative pain after TKR surgery.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Scammell, Brigitte E. Pearson, Richard G.
Keywords:	Pain; Postoperative pain; Knee arthritis; Total knee replacement surgery
Subjects:	W Medicine and related subjects (NLM Classification) > WE Muscoskeletal system
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID:	50659
Depositing User:	Kurien, Thomas
Date Deposited:	28 Sep 2021 14:09
Last Modified:	28 Sep 2021 14:11
URI:	https://eprints.nottingham.ac.uk/id/eprint/50659

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