Characterisation of the neurobiological phenotype of pain in psoriatic arthritis

Sunzini, Flavia (2024) Characterisation of the neurobiological phenotype of pain in psoriatic arthritis. PhD thesis, University of Glasgow.

Abstract

Psoriatic arthritis (PsA) is a prevalent immune-mediated inflammatory arthritis marked by chronic inflammation in both articular and periarticular regions. Advances in understanding the immunopathogenesis have paved the way for the development of advanced immunotherapies, effectively controlling inflammation and the associated tissue damage linked with PsA. Nevertheless, the chronic pain remains a significant issue for individuals with PsA. Chronic pain, frequently linked with musculoskeletal conditions, represents a substantial burden on those affected, leading to diminished quality of life and increased mortality.

The classical pain mechanisms involve damage to peripheral tissues (nociceptive) or peripheral nerves (neuropathic), causing pain. In PsA, nociceptive pain mechanisms are classically considered to prevail, primarily due to peripheral inflammation. Recently, however, a novel pain mechanism, described as nociplastic pain, characterised by dysfunctional nociception processes within the central nervous system (CNS) has been identified. This type of pain lacks evidence of peripheral damage. Fibromyalgia serves as a prototype for nociplastic pain. Specific neurobiological features are identified in fibromyalgia through functional neuroimaging and quantitative sensory testing (QST). Clinically, fibromyalgia (nociplastic pain) appears to co-exist in PsA, however there is no objective evidence to support this observation yet.

This thesis's primary hypothesis is that chronic pain in PsA manifests as a mixed pain state in individuals with a substantial pain burden, potentially explaining the high rates of chronic pain in PsA. To test this hypothesis, this study examines nociplastic pain features and their neurobiological correlations within a wellcharacterised cohort of 50 individuals with PsA with active disease and employing QST and functional MRI to objectively assess nociplastic pain.

The study's evidenced a heightened pressure pain sensitivity at articular and entheseal sites among participants experiencing pronounced nociplastic pain, indicating peripheral sensitisation where inflammation prevails. Observations also unveil altered functional connectivity in subjects with PsA with substantial nociplastic pain, particularly within the insula and DMN regions. Intriguingly, distinct features in the parahippocampal and visual areas predominate within this subgroup, reflecting the complexities of pain perception. This individual and condition-specific diversity defines a distinctive “pain signature”. These findings present an opportunity to pinpoint specific neurobiological markers in PsA.

Despite available evidence suggesting the role of inflammation, the mechanisms sustaining the interaction between the nervous and immune systems remain elusive. Chronic inflammation in rheumatoid arthritis relates to altered connectivity in the inferior parietal lobule (IPL), a similar phenomenon is identified within this study participants with PsA. However, peripheral circulating pro-inflammatory cytokines did not exhibit significant associations with the nociplastic pain neurobiological features investigated in this study.

To date, this study represents the first exploration into the neurobiological features of nociplastic pain in PsA, employing advanced neuroimaging techniques alongside an extensive QST protocol. The findings suggest a distinct pain signature of PsA, sharing characteristics with fibromyalgia and rheumatoid arthritis. To confirm these findings and gain further insights into the role of inflammation in nervous system sensitisation, additional studies are needed. Ultimately, a better understanding of pain mechanisms in PsA will translate into improved patient management and a better quality of life for those affected by this challenging disease.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QR Microbiology > QR180 Immunology
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Supervisor's Name: Basu, Professor Neil and Siebert, Professor Stefan
• Date of Award: 2024
• Depositing User: Theses Team
• Unique ID: glathesis:2024-84187
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 02 Apr 2024 15:22
• Last Modified: 02 Apr 2024 15:30
• Thesis DOI: 10.5525/gla.thesis.84187
• URI: https://theses.gla.ac.uk/id/eprint/84187