Pain sensitization and exercise-induced hypoalgesia in people with knee osteoarthritis

Knee osteoarthritis (OA) is estimated to affect approximately 20% of adults aged ≥ 45 years in Europe and the United States. Pain presentations of people with knee OA have been shown to vary and recent evidence has demonstrated alterations in nociceptive processing in the peripheral and central nervous system of people with knee OA, referred to as pain sensitization; a greater understanding of pain sensitization in knee OA could be integral to the designation and development of appropriate treatment interventions.The overall aim of the thesis was to investigate pain sensitization in people with knee OA using clinically reproducible measures. The aims of the studies were to review the existing evidence for pain sensitization in knee osteoarthritis (OA) (study 1), to further investigate the presence of pain sensitization and to investigate the presence of neural mechanosensitivity (NM) in people with knee OA (study 2 & 3), to investigate potential differences in pain sensitization between subgroups of people with knee OA with high and low pressure pain sensitivity (PPS) (study 4) and to investigate the presence of exercise-induced hypoalgesia (EIH) in response to aerobic and isometric lower limb exercise in people with knee OA with varying degrees of pain sensitization (study 5 & 6).Results from the systematic review and meta-analysis (study 1) indicated that pain sensitization is present in people with knee OA and may be associated with symptom severity. The reliability of lower limb nerve palpation (a measure of NM) was demonstrated (study 2) and case-control studies on knee OA patients with moderate to high symptom severity demonstrated signs of NM using nerve palpation and neurodynamic testing in people with knee OA which had not previously been reported (study 3). In addition, signs of pain sensitization using quantitative sensory testing were demonstrated in people with knee OA, including novel findings of contralateral pain sensitization signs and cold hyperalgesia (study 3); further analysis of results also suggested the presence of higher levels of pain sensitization in a knee OA subgroup with high PPS (study 4). In the first study to investigate EIH in response to aerobic exercise in people with knee OA (study 5), results demonstrated no significant differences between knee OA patients and controls, or between knee OA subgroups with high and low PPS, for EIH in response to aerobic or isometric exercise. However, within-group results suggested a lesser efficiency of EIH in knee OA patients, particularly in those with high PPS, which had not previously been demonstrated. A further study investigated for the first time the effects of isometric and aerobic exercise on EIH in people with knee OA with normal and abnormal conditioned pain modulation (CPM) and demonstrated a dysfunctional EIH response in knee OA patients who had abnormal CPM at baseline (study 6).This thesis provides novel contributions to the body of research regarding pain sensitization in people with knee OA, including findings of NM and signs of contralateral sensitization in knee OA patients. In addition, we demonstrated a greater degree of pain sensitization and decreased efficiency of EIH in knee OA patients with high PPS, and dysfunction of EIH in knee OA patients who exhibit abnormal CPM. These findings have clinical implications regarding the identification of knee OA patients who are pain-sensitized using QST and NM measures, and the appropriate selection of treatment pathways for these patients, including the potential role of an individualised approach to exercise prescription. Further investigation is warranted in relation to identifying knee OA patients with a high degree of pain sensitization; the clinical utility of pain sensitization and NM measures; and the effect of exercise interventions on pain sensitivity in knee OA patients with differing degrees of pain sensitization.