Proteomic analysis of cerebrospinal fluid gives insight into the pain relief of spinal cord stimulation.

Aims Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system affecting approximately 2% of the population. Current pharmacological treatments are ineffective for more than 50% of the patients and often give much adverse effects. Spinal cord stimulation (SCS) is an alternative cost-effective treatment with high efficacy, prolonged pain relief, few side effects. We have compared the cerebrospinal fluid (CSF) proteomes from neuropathic pain patients during pain relief induced by SCS and during pain sensation without SCS, to gain further insights into the mechanisms behind the obtained analgesia. Methods Paired CSF samples were taken from SCS-responsive neuropathic pain patients after the SCS had been turned off for 48 h and when the SCS had been used normally for three weeks. Thus, each patient acted as their own control. The corresponding proteomes for each patient were relatively quantified using a mass spectrometry based shotgun approach. Results In total, 419 unique proteins were simultaneously identified and relatively quantified. A panel consisting of seven proteins, 5 up-regulated and 2 down, were found to be significantly regulated by SCS in two complementary statistical tests (P ≤ 0.01). The most up-regulated protein in the SCS linked panel is a known modulator of nicotinic acetylcholine (ACh) receptor activity. Interestingly, it has a striking tertiary structural similarity and biological functionality as pain modulating prototoxins found in snake venoms. Conclusions Our findings reveal possible insights into the mechanism of spinal cord stimulation and the obtained pain relief.