Arthritis Research & Therapy (Mar 2025)

The insula represents a key neurobiological pain hub in psoriatic arthritis

  • Flavia Sunzini,
  • Kristian Stefanov,
  • Salim Al-Wasity,
  • Chelsea Kaplan,
  • Andrew Schrepf,
  • Noah Waller,
  • Steven Harte,
  • Richard Harris,
  • Daniel J. Clauw,
  • John McLean,
  • Stefan Siebert,
  • Carl S. Goodyear,
  • Gordon D. Waiter,
  • Neil Basu

DOI
https://doi.org/10.1186/s13075-025-03526-7
Journal volume & issue
Vol. 27, no. 1
pp. 1 – 12

Abstract

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Abstract Background Pain remains a principal complaint for people with psoriatic arthritis (PsA), despite successful mitigation of inflammation. This situation alludes to the co-existence of distinct pain mechanisms. Nociceptive and nociplastic mechanisms are clinically challenging to distinguish. Advances in brain functional magnetic resonance imaging (fMRI) have successfully characterised distinct pain mechanisms across several disorders, in particular implicating the insula. This is the first study to characterise neurobiological markers of pain mechanisms in PsA employing fMRI. Methods PsA participants underwent a 6-minutes resting-state fMRI brain scan, and questionnaire assessments of nociplastic pain (2011 ACR fibromyalgia criteria) and body pain, assessed using the Numeric Rating Scale (NRS, 0-100). Functional connectivity between insula seeds (anterior, mid, posterior), and the whole brain was correlated with the above pain outcomes correcting for age and sex, and false discovery rate (FDR) for multiple comparisons. Results A total of 46 participants were included (age 49 ± 11.2; 52% female; FM score 12.5 ± 5.7; overall pain 34.8 ± 23.5). PsA participants with higher fibromyalgia scores displayed increased connectivity between: (1) right anterior insula to DMN (P < 0.05), (2) right mid and left posterior insula to parahippocampal gyri (P < 0.01 FDR); and (3) right mid insula to left frontal pole (P = 0.001 FDR). Overall pain was correlated with connectivity of left posterior insula to classical nociceptive regions, including thalamus (P = 0.01 FDR) and brainstem (P = 0.002 FDR). Conclusion For the first time, we demonstrate objectively that nociceptive and nociplastic pain mechanisms co-exist in PsA. PsA pain cannot be assumed to be only nociceptive in origin and screening for nociplastic pain in the future will inform supplementary analgesic approaches.

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