Osteoarthritis is one of the most prevalent chronic pain conditions, with a lifetime risk of developing knee osteoarthritis (KOA) estimated to be up to 47%. Structural knee damage bears little relationship to pain; thus, evidence is emerging that alterations in nociceptive function contribute to pain. The nociceptive and autonomic nervous systems closely interact and influence each other to modulate pain. Other chronic pain conditions, including fibromyalgia (FM), exhibit autonomic nervous system (ANS) dysfunction. ANS dysfunction may be implicated in OA-related pain, but this has yet to be examined. Therefore, the aim of this thesis was to examine the function of the ANS in people with KOA.

Three studies were designed to investigate autonomic and nociceptive function in people with KOA, people with FM, and healthy, pain free controls at rest and in response to three types of stressors: (1) nociceptive stress, (2) mental stress, and (3) exercise stress. People with FM were included to demonstrate that the experimental procedures were able to detect ANS dysfunction. Quantitative sensory testing, including mechanical and thermal pain thresholds, was used to assess static and dynamic function of the nociceptive system. Heart rate variability was used to assess the parasympathetic nervous system, while impedance cardiography and electrodermal activity were used to assess the sympathetic nervous system. Assessments were made before, during, and after exposure to the stressors.

Static mechanical and thermal pain thresholds were not different in the KOA and FM groups in any of the studies. However, consistent evidence of resting ANS dysfunction was found in the KOA and FM groups compared to controls. People with KOA demonstrated reduced vagal tone at rest, but additionally showed reduced vagal withdrawal in response to nociceptive stress, acute mental stress, and acute exercise stress. There was some evidence of sympathetic hyperactivity at rest in the KOA and FM groups, as well as some evidence of a ceiling effect of blunted sympathetic reactivity when exposed to acute stress. Cardiac sympathetic reactivity was found to be dampened in people with KOA in response to both nociceptive and exercise stress. The findings of reduced tonic vagal activity, elevated resting sympathetic activity, and reduced autonomic modulation in response to stress raise the potential of a blunted ability to adapt to stress and modulate nociception. In support of this, in response to nociceptive stress, acute mental stress, and acute exercise stress, people with KOA and people with FM demonstrated an impairment of conditioned pain modulation, mental stress-induced hypoalgesia, and exercise-induced hypoalgesia, respectively.

These studies are the first to show evidence of ANS dysfunction in people with KOA at rest, and in response to three types of stressors. The results suggest that people with KOA may be less adept at responding to stress due to diminished autonomic flexibility, and at risk of impaired modulation of nociception when exposed to acute stress. These findings offer potential for future research to investigate ways to normalise ANS function and examine the impact on KOA pain.