Cathepsin S is increased in cerebrospinal fluid from patients with neuropathic pain—A support of the microglia hypothesis in humans

Aims Cathepsin S has been reported to be a biomarker of spinal microglial activation, a process suggested to be involved in the pathophysiology of chronic neuropathic pain. So far this has been shown only in animal experiments. The aim of this study was to investigate the concentrations of cathepsin S in human cerebrospinal fluid (CSF) samples from a well-defined patient cohort suffering from neuropathic pain as compared to controls. Methods CSF samples from patients suffering from chronic neuropathic pain (n = 14) were analyzed for cathepsin S levels using commercial sandwich ELISAs (DY1183, R&D Systems, Minneapolis, MN, USA). Control CSF was sampled from patients undergoing minor urological surgical procedures under spinal anaesthesia (n = 70), having no obvious pain suffering. Results The neuropathic pain group had significantly higher levels of CSF cathepsin S (median 15189 pg/mL, range 3213-40,040), than the control group (median 5911 pg/mL, range 1909-17,188) (p < 0.005, Mann-Whitney U-test). Conclusion The results support the existence of microglial activation in chronic neuropathic pain patients. CSF Cathepsin S may serve as a potential biomarker for this specific mechanism linked to neuropathic pain. In the future, Cathepsin S inhibiting drugs might become a new treatment alternative for neurophatic pain.