Alexander Rosenström, MD1, Aisha Siddiqah Ahmed, PhD2, Kim Kultima, PhD3, 4, Eva Freyhult, PhD5, Svante Berg, MD, PhD2, Vinko Palada, PhD6, Camilla I. Svensson, PhD*, Eva Kosek, MD, PhD1, 7  *
* Both contributed equally

  1. Department of surgical sciences, Uppsala university
  2. Department of molecular medicine and surgery, Karolinska Institute
  3. Department of medical sciences, Uppsala university
  4. Department of physiology and pharmacology, Karolinska Institute
  5. Department of cell and molecular biology, Uppsala university
  6. Department of Physiology, University of Helsinki
  7. Department of clinical neuroscience, Karolinska Institute

Background Recent evidence highlights the importance of the neuroimmune interface, including periphery-to-CNS neuroimmune crosstalk, in chronic pain. While neuroinflammatory processes have been implicated in central sensitization for a long time, their potential neuroprotective and analgesic effects remain relatively elusive.

Aim: We’ve investigated the relationships between cytokine release and symptom severity, and explore possible candidates for periphery-to-CNS crosstalk.

Method: Patients with degenerative disc disease (DDD) (nociceptive pain) or patients with lumbar disc herniation (LDH) with radiculopathy (predominantly neuropathic pain) completed questionnaires regarding pain and functional disability, underwent quantitative sensory testing, and provided blood and CSF samples. Proximity extension assay (PEA) was used to measure the levels of 92 inflammatory proteins in the CSF and serum from a total of 160 patients and controls.

Resultat: Several cytokines were upregulated in the CSF of both patient groups compared to controls, indicating neuroimmune activation, while serum protein expression was generally downregulated compared to controls. Regarding periphery-to-CNS neuroimmune crosstalk, several cytokines, including CCL11, CD5, IL8, and MMP-10, were elevated in the CSF also had positive correlations between CSF and serum levels. These cytokines were also associated with back, but not leg, pain intensity in the LDH group and none with back pain intensity in DDD patients. The association between CSF cytokines and pain was complex.

Conclusion: In conclusion, we found evidence for neuroimmune activation in the CNS of both patient groups in the absence of systemic inflammation, and signs of a communication between CSF and serum. Complex and disease-specific associations were found between cytokines in CSF and back pain intensity.