Examination and characterisation of the effect of amitriptyline therapy for chronic neuropathic pain on neuropeptide and proteomic constituents of human cerebrospinal fluid

AbstractAimsCathepsin 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.MethodsCSF 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.ResultsThe 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).ConclusionThe 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.

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Cerebrospinal fluid levels of substance P (SP) N-terminal fragment SP1–7 in patients with neuropathic pain

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2015.04.014 ◽

2015 ◽

Vol 8 (1) ◽

pp. 51-51

Author(s):

A. Jonsson ◽

A.-L. Lind ◽

M. Hallberg ◽

F. Nyberg ◽

T. Gordh

Keyword(s):

Cerebrospinal Fluid ◽

Neuropathic Pain ◽

Substance P ◽

Chronic Neuropathic Pain ◽

Painful Condition ◽

Mechanical Hypersensitivity ◽

Terminal Fragment ◽

Minor Surgery ◽

Fluid Levels ◽

Pain Patients

Abstract Aims Neuropathic pain is a complex and painful condition, which is difficult to treat and causes a lot of suffering. The substance P (SP) system is well known to be involved in nociceptive signaling and it has previously been shown that the cerebrospinal fluid (CSF) level of SP is decreased in neuropathic pain. In this study we analyzed CSF from chronic neuropathic pain patients for the levels of SP1–7, an N-terminal fragment of SP with the ability to alleviate thermal as well as mechanical hypersensitivity in different animal models of chronic neuropathic pain, e.g. [1,2]. Methods CSF was collected from 11 neuropathic pain patients, treated with SCS, who had refrained from using their spinal cord stimulator for 48h. Control CSF was collected from 11 patients without any known neurological disorder, who underwent minor surgery under spinal anesthesia. The CSF samples were analyzed for the levels of SP1–7 using radioimmunoassay. Results The results revealed a decrease in the level of SP1–7 compared to controls. We believe that the lower level ofSP1–7 most likely is a consequence of reduced amount of its precursor SP in the neuropathic pain patients. Conclusions Our results indicate that the SP system is changed in patients with neuropathic pain and that SP-related peptides, including SP1–7, might serve as biological markers for the patho-physiology of chronic neuropathic pain.

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