Identifying and treating cognitive impairment in fibromyalgia and chronic widespread pain: an epidemiological study and a feasibility study

Thesis

Fibromyalgia is a chronic pain condition characterised by widespread pain in the presence of symptoms including sleep disturbance and cognitive difficulties, also known as “fibrofog”. It is the prototypical example of nociplastic pain, which arises from dysfunctional pain processing in the central nervous system, notably in the descending pain modulation system (DPMS). Nociplastic pain exists on a spectrum, with varying degrees of pain widespreadness and other symptoms such as sleep disturbance. Although cognitive difficulties are common in these disorders, the long-term cognitive consequences are uncertain, as is the role of sleep. Cognitive symptoms in insomnia can be successfully treated with cognitive behavioural therapy for insomnia (CBT-I), which thus represents a promising therapeutic approach for alleviating cognitive difficulties in fibromyalgia.

The aim of this thesis was to investigate the relationship between fibromyalgia, nociplastic pain, and cognitive impairment, with a particular focus on sleep disturbances. This was achieved through two key studies: an epidemiological study of nociplastic pain and cognition in UK Biobank, a large population-based cohort study of middle-age British adults; and an observational study evaluating sustained attention in patients with fibromyalgia, with an embedded feasibility trial of digital CBT-I (PainLESS).

In UK Biobank, nociplastic pain severity was shown to have a cross-sectional association with worse executive function but was not associated with faster decline in cognitive abilities. This cross-sectional relationship was mediated by pain intensity and sleep disturbance. In the same cohort, I also showed that nociplastic pain was associated with altered functional and structural connectivity within the DPMS, which in turn mediated the relationship with executive function.

In a cohort of patients with fibromyalgia, symptom severity was associated with impaired sustained attention, which in turn was also mediated by sleep disturbance and altered connectivity within the DPMS on neuroimaging.

Finally, a trial of digital CBT-I nested within this cohort was feasible in fibromyalgia.

The work in this thesis therefore demonstrates that sleep disturbance contributes to cognitive impairment in fibromyalgia, representing a promising therapeutic target. A trial of digital CBT-I in fibromyalgia may improve cognitive outcomes in future patients with the disorder.

Authors: Kelleher, E

• DOI: 10.5287/ora-brjpdbje1
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: chronic pain; Cognitive Behavioural Therapy for Insomnia; UK Biobank; sleep; epidemiology; neuroimaging; nociplastic pain; fibromyalgia
• Subjects: Cognitive therapy; Chronic pain; Epidemiology; Fibromyalgia; Chronic pain--Treatment