Conclusion
The CSF secretome and proteome was modulated in responders to amitriptyline verifying many pre-clinical and in vitro models. The predominant features were immunomodulation with a reduction in pro-inflammatory pathways of neuronal-glia communications and evidence of a neurotrophic effect.
Methods
Patients with lumbar radicular neuropathic pain were selected for inclusion with clinical and radiological signs and a >50% reduction in pain in response to a selective nerve root block. Baseline (pre-treatment) and 8-week (post-treatment) pain scores with demographics were recorded. CSF samples were taken at baseline (pre-treatment) and 8 weeks after amitriptyline treatment (post-treatment). Proteome analysis was performed using mass spectrometry and secreted cytokines, chemokines and neurotrophins were measured by enzyme-linked immunosorbent assay (ELISA).
Results
A total of 9/16 patients experienced a >30% reduction in pain after treatment with amitriptyline and GO analysis demonstrated that the greatest modulatory effect was on immune system processes. KEGG analysis also identified a reduction in PI3K-Akt and MAPK signalling pathways in responders but not in non-responders. There was also a significant decrease in the chemokine eotaxin-1 (p = 0.02) and a significant increase in the neurotrophin VEGF-A (p = 0.04) in responders.