Predictors of Persistent Pain following Total Knee Arthroplasty
Year: 2026
Type: dissertation
Study design: Observational Study
Abstract: Knee osteo-arthritis (KOA) has been categorised as a separate condition from other knee conditions since the mid-twentieth century. Effective treatment has been hampered by inconsistent categorisation and heterogenous aetiology. Emerging research indicates that KOA is not purely a degenerative condition related to load, age and biomechanics. Rather, KOA appears to be strongly influenced by the neuro-immune system. Metabolic factors induce release of pro-inflammatory cytokines which initiate a cascade of cellular responses resulting in cartilage degradation. Age, weight, sex and biomechanical factors appear to exacerbate these changes. The pro-inflammatory cytokines IL-6, TNF-α, and IL-1β appear to be the most influential cytokines in this process. Pain is a perception that is felt in response to threat. Each individual’s experience is unique so that perception of threat varies according to the individual’s experiences, beliefs and cognitions. Within the nervous system, the physiological response to threat is mediated in part, by cytokines. Pro-inflammatory cytokines such as IL-6, IL-1β and TNF-α are implicated in the signalling processes that modulate these responses. The resultant neuroplastic changes can be short or long-term. In the early stages of KOA radiological changes are not consistently associated with pain. As radiological changes progress pain becomes more consistently correlated. Pro-inflammatory cytokines notably IL-6 appear to be associated with both progression of OA and pain. This persistent pain associated with neuroplastic changes within the nervous system is called central sensitisation (CS). CS results in a lowered threshold to mechanical, thermal and chemical input resulting in: Hyperalgesia - increased pain from a stimulus that normally provokes pain. (IASP, 2021) Allodynia - pain due to a stimulus which does not normally provoke pain (IASP, 2021; Loeser & Treede, 2008). Definitive treatment for KOA is total knee arthroplasty (TKA), however, up to 22% of people undergoing TKA have ongoing pain often associated with unresolved CS. IL-6 appears to be involved in these processes; however, its exact role has not been elucidated in TKA. IL-6 is regarded as ubiquitous and pleiotropic, initially thought of as only inflammatory, recent evidence indicates that its effect can be either pro or anti-inflammatory in different scenarios. For example, TNF-α expression up-regulates IL-6 expression and has a pro-inflammatory influence, while exercise induces expression of IL-6 from muscle tissue which inhibits TNF-α and is anti-inflammatory in effect especially in relation to the metabolic processes that induce cartilage degradation in KOA. This thesis comprises three studies which examine the relationship between the various methods of assessing CS over a six-month post-TKA time course, in order to understand how each method of assessment inter-relates and contributes to a patient’s outcome. Study one contextualises the outcomes of patients undergoing TKA in a regional setting, we establish that access to TKA, despite longer wait times than city-based populations, does not impact outcomes compared to similar national and international cohorts. Through this study it was established that our participants are representative of general TKA populations and are therefore a valid group to study CS following TKA. Study two examined the intersection between plasma and salivary measures of pro-inflammatory cytokines with patient reported outcomes (PRO) over the six-month post-TKA time-course. Results indicated an unexpected rise in IL-6 and poor correlation with PRO. Finally, markers of CS were examined, namely quantitative sensory testing (QST); plasma cytokines and PRO at four time points; less than one month pre-operatively and at one, three and six months post-operatively, and found poor association between all markers of CS. These are novel findings that challenge contemporary theories of CS following TKA.
Author: Roberts, John
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7204281038