285: Fibromyalgia is associated with a higher blood-brain barrier permeability than other pain conditions

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic primary musculoskeletal pain, Neuroimmunology

Background and Aims: Fibromyalgia is associated with neuroimmune activation [2] and increased glia cell activity [1]. In fact, chronic pain in general is associated with an alteration of the neuroimmune environment [3] - a compartment that has potential to both affect and be affected by the blood-brain barrier. However, the distribution of BBB permeability across pain conditions, and the discrepancies between them, are knowledge gaps that will be important to close for the sake of our understanding of peripheral-central neuroimmune crosstalk and its potential mechanistic contributions to the pathophysiology of different kinds of chronic pain.

Methods: We included 65 female patients with fibromyalgia meeting ACR1990 and ACR2016 criteria. In addition, female patients with radiologically verified degenerative disc disease (DDD, n = 24), lumbar disc herniation (LDH, n = 12) and osteoarthritis (OA, n = 13), all awaiting surgery, were included. LDH patients needed to have leg pain as their dominant complaint. CSF controls were either patients undergoing neurological workup without subsequent neurological disorder (n = 31) or healthy control subjects (n = 11) participating in research.

Group differences were evaluated using non-parametric methods. The presented p-values are adjusted using the Holm–Bonferroni method.

Results: In each respective cohort, namely, FM, DDD, LDH, OA and CSF controls, the CSF-serum albumin quotients were 5.4 ± 2.0, 3.5 ± 1.4, 3.4 ± 1.9, 3.7 ± 1.5 and 4.4 ± 1.7, respectively. The CSF-serum albumin quotient was significantly different between groups (p = 1.1E-6), corresponding to an effect size eta^2 = 0.19 (large). Post hoc tests revealed that fibromyalgia patients exhibited significantly higher blood-brain permeability than all other groups (DDD: p < 0.001; OA, LDH, NINS: p < 0.01).

Conclusions: In the ”subclinical” stratum, FM patients have higher albumin quotients than the other groups of patients. Considering previous reports on 1) the association between BBB permeability and CSF cytokines, and 2) the association between chronic pain conditions and alterations in the neuroimmune environment, this finding raises interesting mechanistic questions related to the interplay between the immune and nervous systems.

References: [1] Albrecht DS, Forsberg A, Sandström A, Bergan C, Kadetoff D, Protsenko E, Lampa J, Lee YC, Höglund CO, Catana C, Cervenka S, Akeju O, Lekander M, Cohen G, Halldin C, Taylor N, Kim M, Hooker JM, Edwards RR, Napadow V, Kosek E, Loggia ML. Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation. Brain Behav Immun 2019;75:72–83.

[2] Kadetoff D, Lampa J, Westman M, Andersson M, Kosek E. Evidence of central inflammation in fibromyalgia-increased cerebrospinal fluid interleukin-8 levels. J Neuroimmunol 2012;242:33–38.

[3] Rosenström AHC, Konsman J-P, Kosek E. Cytokines in Cerebrospinal Fluid and Chronic Pain in Humans: Past, Present, and Future. Neuroimmunomodulation 2024;31:157–172.

Presenting Author: Alexander Rosenström
Submitting Author: Alexander Rosenström

Senior Author: Camilla Svensson, Eva Kosek

IASP 2026 Global Year theme of Neuropathic Pain: No

• Martin Flores Bjurström: M.D., Ph.D. - Uppsala University
• Aisha Siddiqah Ahmed: Ph.D. - Karolinska Institutet
• Alex Bersellini Farinotti: Ph.D. - Karolinska Institutet
• Camilla I Svensson: Ph.D. - Karolinska Institutet
• Eva Kosek: M.D., Ph.D. - Uppsala University, Karolinska Institutet